VRC 322/DMID 21-0016: A Phase I, Dose Escalation, Open-Label Clinical Trial to Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, mRNA-1215, in Healthy Adults
Phase: PHASE1
Conditions: Nipah Virus Infection
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Protocol Title: VRC 322 (000687): A Phase I, Dose Escalation, Open-Label Clinical Trial to 
Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, 
mRNA-1215, in Healthy Adults 
NCT:05398796 
 
Documents: 
· IRB-approved Protocol (v5.0 20DEC2023) - Statistical Analysis Considerations located 
in Section 6 of the Protocol  
· Final IRB-approved Main Informed Consent (v4.0 20DEC2023) -  
IRB Approval/Document Date:28DEC2023 

 
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VACCINE RESEARCH CENTER 
 
 
A Phase I, Dose Escalation, Open-Label Clinical Trial to Evaluate Safety, Tolerability and 
Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, mRNA-1215, in Healthy Adults 
 
Abbreviated Title:  NiV mRNA-1215 vaccine 
 
DMID Protocol Number: 21-0016 
NIH 000687 
IND 28335 
IND Sponsor: Division of Microbiology and Infectious Diseases (DMID) 
 
Investigational Product, mRNA-1215, Manufacturer:  ModernaTX 
 
Version Number:  5.0 
 
December 20, 2023 
 
 
 
 
 
 
 
 
 
 
 
NIH Principal Investigator: 
Lesia Dropulic, M.D.  
VRC/NIAID 
 
 
 
 
 

 
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STATEMENT OF COMPLIANCE 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training.  
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval. Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled. Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study. In addition, all changes to the consent form will be IRB-approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form.  
The study will be carried out in accordance with the following as applicable: 
• United States Code of Federal Regulations (CFR) 45 CFR Part 46: Protection of Human 
Subjects 
• Food and Drug Administration (FDA) Regulations: 21 CFR Part 50 (Protection of 
Human Subjects), 21 CFR Part 54 (Financial Disclosure by Clinical Investigators), 21 
CFR Part 56 (Institutional Review Boards), 21 CFR Part 11, and 21 CFR Part 312 
(Investigational New Drug Application), and/or 21 CFR 812 (Investigational Device 
Exemptions) 
• The International Council for Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use (ICH) E6(R2) Good Clinical Practice, and the 
Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects 
of Research, Report of the National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research 
• The policies and procedures of National Institutes of Health (NIH) Office of Extramural 
Research and DMID 
• The National Institute of Allergy and Infectious Diseases (NIAID)  
• Any additional Federal, State, and Local Regulations and Guidance 
 
 
 

 
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PROTOCOL SIGNATURE PAGE 
 
VRC 322/DMID 21-0016: A Phase I, Dose Escalation, Open-Label Clinical Trial to 
Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, 
mRNA-1215, in Healthy Adults 
 
I, the Principal Investigator for the study site indicated below, agree to conduct the study in full 
accordance with the provisions of this protocol and all applicable protocol-related documents.  I 
agree to conduct the study in compliance with United States (US) Health and Human Services 
(HHS) regulations (45CFR 46); applicable US Food and Drug Administration (FDA) 
regulations; standards of the International Council for Harmonization Guidelines for Good 
Clinical Practice (E6); Institutional Review Board/Ethics Committee (IRB/EC) determinations; 
all applicable in-country, state, and local laws and regulations; and other applicable requirements 
(e.g., US National Institutes of Health) and institutional policies.  I will comply with all 
requirements regarding the obligations of investigators as outlined in the Statement of 
Investigator (Form FDA 1572), which I have also signed.  I agree to maintain all study 
documentation pertaining to the conduct of this study, including, but not limited to, case report 
forms, source documents, laboratory test results, and medication inventory records, per FDA 
regulation (21 CFR 312.62) and all applicable requirements.  The protocol signature page will be 
signed for subsequent protocol approvals.  No study records will be destroyed without prior 
authorization from VRC/NIAID.  
Publication of the results of this study will be governed by the VRC/NIAID and DMID/NIAID 
policies. Any presentation, abstract, or manuscript will be made available by the investigators to 
VRC, DMID and Moderna leaderships for review prior to submission.  I have read and 
understand the information in this protocol and will ensure that all associates, colleagues, and 
employees assisting in the conduct of the study are informed about the obligations incurred by 
their contribution to the study. 
 
Lesia Dropulic, MD  
VRC / Vaccine Evaluation Clinic (VEC) 
Name/Title of Principal Investigator 
Investigator Study Site Name 
 
 
__________________________________             __________________________________ 
Signature of Principal Investigator                            Date 
 
 
 
 
 
 
 
 

 
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TABLE OF CONTENTS 
1. 
INTRODUCTION ................................................................................................................ 12 
1.1 
Study Rationale ............................................................................................................. 12 
 
Rationale for Development of NiV mRNA-1215 Vaccine ................................... 12 
 
Rationale for mRNA-1215 Vaccine Dose and Regimen ...................................... 13 
1.2 
Background ................................................................................................................... 14 
1.2.1 
Previous Human Experience with mRNA-based Vaccines .................................. 14 
1.2.2 
Preclinical Studies with mRNA-1215 Vaccine..................................................... 14 
1.2.3 
Human Experience with mRNA-1215 Vaccine .................................................... 14 
1.3 
Laboratory Assessment of mRNA-1215 Vaccine Immunogenicity ............................. 16 
 
Interim Evaluation of the mRNA-1215 Vaccine Immunogenicity ....................... 17 
2. 
STUDY PRODUCTS ........................................................................................................... 18 
2.1 
mRNA-1215 Vaccine.................................................................................................... 18 
2.2 
Diluent: 0.9% NaCl for injection, USP ......................................................................... 18 
3. 
STUDY OBJECTIVES ......................................................................................................... 19 
3.1 
Primary Objectives........................................................................................................ 19 
3.2 
Secondary Objectives.................................................................................................... 19 
3.3 
Exploratory Objectives ................................................................................................. 19 
4. 
SUBJECT POPULATION AND CLINICAL PROCEDURES ........................................... 20 
4.1 
Overall Study Design .................................................................................................... 20 
4.2 
Study Population ........................................................................................................... 20 
 
Inclusion Criteria .................................................................................................. 20 
 
Exclusion Criteria ................................................................................................. 21 
4.3 
Inclusion of Vulnerable Subjects .................................................................................. 22 
 
Pregnant Women ................................................................................................... 22 
 
Children................................................................................................................. 23 
 
Adult Subjects who Lack the Capacity to Consent ............................................... 23 
 
NIH Employees ..................................................................................................... 23 
4.4 
Clinical Procedures and Evaluation .............................................................................. 23 
 
Recruitment and Retention Strategies ................................................................... 24 
 
Costs ...................................................................................................................... 24 
 
Compensation ....................................................................................................... 24 
 
Screening............................................................................................................... 24 
 
Study Schedule...................................................................................................... 25 
 
Enrollment and Day 0 ........................................................................................... 25 
 
Birth Control and Pregnancy ................................................................................ 25 
 
Vaccine Administration ........................................................................................ 26 
 
Post-Product Administration Follow-Up .............................................................. 26 
 
Solicited Adverse Events (Reactogenicity) .......................................................... 26 
 
Follow-up through End of Study .......................................................................... 27 
 
Blood Sample Collection ...................................................................................... 27 

 
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Apheresis............................................................................................................... 27 
 
Apheresis Eligibility Criteria ................................................................................ 28 
 
Concomitant Medications ..................................................................................... 29 
4.5 
Criteria for Dose Escalation .......................................................................................... 29 
4.6 
Group 4 Dose Selection ................................................................................................ 30 
4.7 
Criteria for Discontinuing Protocol Participation ......................................................... 30 
4.8 
Discontinuing Second Vaccination ............................................................................... 30 
4.9 
Criteria for Pausing and Resuming the Study ............................................................... 31 
 
Plan for Pausing the Study .................................................................................... 31 
 
Plan for Review of Pauses and Resuming the Study ............................................ 32 
5. 
SAFETY AND ADVERSE EVENT REPORTING ............................................................. 33 
5.1 
Adverse Events ............................................................................................................. 33 
5.2 
Serious Adverse Events ................................................................................................ 33 
5.3 
Adverse Event Reporting to the IND Sponsor .............................................................. 34 
5.4 
Adverse Events of Special Interest (AESI) ................................................................... 34 
 
Anaphylaxis .......................................................................................................... 35 
 
Myocarditis and Pericarditis ................................................................................. 35 
5.5 
Medically Attended Adverse Events (MAAEs) ........................................................... 35 
5.6 
Reporting of Serious Adverse Events to DMID Pharmacovigilance............................ 35 
5.7 
Reporting of Pregnancy ................................................................................................ 36 
5.8 
IND Sponsor Reporting to the FDA ............................................................................. 36 
5.9 
Reporting to the Institutional Review Board ................................................................ 37 
 
Unanticipated Problem.......................................................................................... 37 
 
Non-Compliance ................................................................................................... 38 
 
Protocol Deviation ................................................................................................ 38 
 
Death ..................................................................................................................... 39 
 
New Information ................................................................................................... 39 
 
Suspension or Termination of Research Activities ............................................... 39 
 
Expedited Reporting to the IRB ............................................................................ 39 
 
Annual Reporting to the IRB ................................................................................ 39 
6. 
STATISTICAL CONSIDERATIONS.................................................................................. 40 
6.1 
Overview ....................................................................................................................... 40 
6.2 
Sample Size and Accrual .............................................................................................. 40 
6.3 
Endpoints ...................................................................................................................... 40 
 
Primary Endpoints: Safety .................................................................................... 40 
 
Secondary Endpoints: Immunogenicity ................................................................ 40 
 
Exploratory Endpoints: Immunogenicity .............................................................. 40 
 
Sample Size Consideration for Safety .................................................................. 40 
 
Sample Size Consideration for Immunogenicity .................................................. 42 
 
Sample Size Consideration for Comparison ......................................................... 42 
6.4 
Statistical Analysis ........................................................................................................ 42 
 
Analysis Variables ................................................................................................ 42 
 
Baseline Demographics ........................................................................................ 42 

 
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Safety Analysis ..................................................................................................... 43 
6.4.3.1 
Solicited Reactogenicity ................................................................................... 43 
6.4.3.2 
Adverse Events ................................................................................................. 43 
6.4.3.3 
Local Laboratory Values................................................................................... 43 
 
Immunogenicity Analysis ..................................................................................... 43 
 
Missing Data ......................................................................................................... 43 
 
Interim Analyses ................................................................................................... 44 
7. 
PHARMACY AND VACCINE ADMINISTRATION PROCEDURES ............................. 45 
7.1 
mRNA-1215 Vaccine, Pharmaceutical Formulation .................................................... 45 
7.2 
Vaccine Storage ............................................................................................................ 45 
 
Handling Information............................................................................................ 45 
 
Temperature Excursions ....................................................................................... 45 
7.3 
Preparation of mRNA-1215 for Administration ........................................................... 46 
 
Dose Preparation ................................................................................................... 46 
7.4 
Administration of mRNA-1215 Injection ..................................................................... 47 
7.5 
Study Product Accountability ....................................................................................... 47 
 
Documentation ...................................................................................................... 47 
 
Disposition ............................................................................................................ 47 
8. 
HUMAN SUBJECT PROTECTIONS AND ETHICAL OBLIGATIONS .......................... 48 
8.1 
Institutional Review Board ........................................................................................... 48 
8.2 
Informed Consent.......................................................................................................... 48 
8.3 
Study Discontinuation and Closure .............................................................................. 48 
8.4 
Confidentiality and Privacy .......................................................................................... 49 
8.5 
Risks and Benefits Assessment ..................................................................................... 50 
 
Risks of mRNA-1215 ........................................................................................... 50 
 
Risks of Specimen Collection ............................................................................... 50 
 
Risks of mRNA-1215 for the Fetus or Nursing Infant ......................................... 51 
 
Risks of New Diagnoses ....................................................................................... 51 
 
Potential Benefits .................................................................................................. 51 
 
Assessment of Potential Risks and Benefits ......................................................... 51 
8.6 
Plan for Use and Storage of Biological Samples .......................................................... 52 
 
Use of Samples, Specimens and Data ................................................................... 52 
 
Storage and Tracking of Blood Samples and Other Specimens ........................... 52 
 
Disposition of Samples, Specimens and Data at Completion of the Protocol ...... 52 
 
Loss or Destruction of Samples, Specimens or Data ............................................ 53 
8.7 
Safety Oversight............................................................................................................ 53 
 
Protocol Safety Review Team .............................................................................. 53 
 
Safety Monitoring Committee (SMC) .................................................................. 53 
9. 
ADMINISTRATIVE AND OPERATIONAL OBLIGATIONS .......................................... 55 
9.1 
Protocol Amendments ................................................................................................... 55 
9.2 
Study Documentation and Storage ................................................................................ 55 
9.3 
Clinical Monitoring ....................................................................................................... 55 
9.4 
Data Collection and Data Sharing................................................................................. 56 

 
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Data Collection ..................................................................................................... 56 
 
Source Documents ................................................................................................ 56 
 
Data Sharing Plan ................................................................................................. 56 
9.5 
Quality Assurance and Quality Control ........................................................................ 56 
9.6 
Language ....................................................................................................................... 56 
9.7 
Research-Related Injuries ............................................................................................. 57 
10. 
REFERENCES ................................................................................................................. 58 
APPENDIX I: SCHEDULE OF EVALUATIONS ...................................................................... 61 
APPENDIX II: ASSESSMENT OF RELATIONSHIP TO VACCINE AND GRADING 
SEVERITY OF ADVERSE EVENTS ......................................................................................... 66 
APPENDIX III: ADVERSE EVENTS OF SPECIAL INTEREST TERMS ............................... 74 
 
 
 

 
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LIST OF TABLES 
 
Table 1: VRC 322/DMID 21-0016 Study Schema ....................................................................... 20 
Table 2: Probability of Observing Events under Different Scenarios within a Group (n=10) ..... 41 
Table 3: 95% Confidence Intervals for True Rate under Possible Observed Number of Events . 41 
Table 4: Minimum Event Rate That Can Be Detected With 80% Or 90% Power with Sample 
Size n=10 per Arm ........................................................................................................................ 42 
Table 5: mRNA-1215 Injection Dose Preparation Schema .......................................................... 47 
Table 6: AESI Categories ............................................................................................................. 75 
Table 7: Case Definitions of Probable and Confirmed Myocarditis, Pericarditis, and 
Myopericarditis ............................................................................................................................. 76 
 
 
 
 
 

 
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ABBREVIATIONS 
Abbreviation
Definition
ADA 
Anti-Drug Antibody
AE 
Adverse event 
AoU
Assessment of Understanding
ALP 
Alkaline phosphatase
ALT
Alanine aminotransferase
AST 
Aspartate aminotransferase 
BD
Bangladesh strain
CBC
Complete blood count
CDC 
Centers for Disease Control and Prevention 
CEPI 
Coalition for Epidemic Preparedness Innovations
cGMP 
current Good Manufacturing Practices 
CMP
Clinical Monitoring Plan
CTP
Clinical Trials Program
DMID
Division of Microbiology and Infectious Diseases
FDA
Food and Drug Administration
GCP
Good Clinical Practice 
GMT
Geometric Mean Titer 
ICF
Informed Consent Form 
ICH 
International Council for Harmonisation
IM 
Intramuscular Injection 
IND 
Investigational New Drug Application 
IND SAR 
Investigational New Drug Application Sponsor’s Authorized Representative
IRB
Institutional Review Board
IUD 
Intrauterine device
LNP 
Lipid Nanoparticle  
MAAE
Medically attended adverse event 
MedDRA 
Medical Dictionary for Regulatory Activities
MM 
Medical Monitor
MY 
Malaysian strain
NaCl
Sodium Chloride
NHP
Non-human primate
NIAID 
National Institute of Allergy and Infectious Diseases  
NIH 
National Institutes of Health
NIH CC
National Institutes of Health Clinical Center 
NiV 
Nipah virus 
PBMC
Peripheral blood mononuclear cell
PCR 
Polymerase Chain Reaction
PI 
Principal Investigator
PSRT
Protocol Safety Review Team 
QA
Quality Assurance 

 
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Abbreviation
Definition
SAE 
Serious adverse event
SC 
Subcutaneous
SMC
Safety Monitoring Committee
SUSAR
Serious and unexpected suspected adverse reaction
U.S. 
United States 
ULN 
Upper limit of normal 
VEC
Vaccine Evaluation Clinic 
VRC 
Vaccine Research Center 
VIP 
Vaccine Immunology Program
VRC 
Vaccine Research Center 
WBC 
White blood cells  
WHO
World Health Organization
 
 
 
 

 
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    PRÈCIS 
 
Title: 
VRC 322/DMID 21-0016: A Phase I, Dose Escalation, Open-Label Clinical Trial to 
Evaluate Safety, Tolerability, and Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, 
mRNA-1215, in Healthy Adults 
Design:   
This Phase I, dose escalation, open label clinical trial is the first study of mRNA-1215 in 
healthy adults to evaluate the safety, tolerability, and immunogenicity of a Nipah virus (NiV) 
mRNA vaccine. The hypotheses are that the vaccine will be safe, tolerable, and will elicit an 
immune response in healthy adults.  
Study 
Product:   
mRNA-1215 is a novel mRNA vaccine that encodes for the secreted prefusion stabilized F 
component covalently linked to G monomer (pre-F/G) of Malaysian strain NiV, resulting in 
a post-expression trimerization. mRNA-1215 was co-developed by the Vaccine 
Research Center (VRC), National Institute of Allergy and Infectious Disease 
(NIAID) and ModernaTX, Inc, and manufactured by ModernaTX. 
Subjects: 
Healthy adults, 18 to 60 years of age.  
Plan: 
Subjects will be enrolled at the NIH Clinical Center and will receive mRNA-1215 via 
intramuscular (IM) injection by needle and syringe into the deltoid muscle. A dose escalation 
safety evaluation will occur to ensure the safety data support proceeding to the higher dose 
group. The mRNA-1215 vaccine dose for Group 4 was selected based on interim analysis of 
safety and immunogenicity data from Groups 1-3. Subjects will be evaluated for safety and 
immune responses through clinical observation and blood collection at specified timepoints 
throughout the study. The study schema is as follows: 
 
 
 
 
 
 
 
 
Duration:      Subjects will be evaluated for safety and immune responses throughout the study for 52 
weeks following last product administration. 
 
 
 
Study Schema
Group
Subjects 
Dose/Route
Day 0
Week 4
1
10
25 mcg IM 
X 
X
2
10
50 mcg IM 
X 
X
3
10
100 mcg IM
X 
X
4
10
10 mcg IM 
X 
X
Total  
140  
1Enrollment up to 50 subjects is permitted in case additional 
evaluations are required for safety or immunogenicity.  

 
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1. 
INTRODUCTION  
The Nipah virus (NiV) is a zoonotic single-stranded, negative sense RNA virus belonging to the 
Paramxyxoviridae family, genus Henipavirus, which also includes Hendra virus (HeV) and 
Cedar virus (CedPV). NiV and HeV cause fatal disease in humans while CedPV has not been 
found to be pathogenic in any animal [1]. Two different strains of NiV have been identified, the 
Malaysian (MY) and the Bangladesh (BD) strains. The two strains are approximately 92% 
identical in sequence but appear to be significantly different in their pathogenicity and 
transmissibility [2]. The MY strain of NiV is primarily encephalitic with no documented cases of 
person-to-person transmission [3]. While most cases result from zoonotic transmission, the BD 
strain of NiV can also spread person-to-person via respiratory (droplet) transmission [4-9]. 
Research in non-human primates (NHP) and ferrets has shown there is a more rapid onset of 
productive infection and higher levels of virus replication in respiratory tract tissues observed 
after NiV-BD infection compared to NiV-MY infection[10-12]. In addition, NiV-BD infection in 
humans resulted in a higher mortality rate compared to NiV-MY. This difference could be 
attributed to inadequate regional medical care[13]. Infection in humans is neurotropic, and 
patients often develop fatal encephalitis [14-19]. NiV can cause illness in horses and other 
domestic animals such as dogs, cats and goats which increases the probability of zoonotic 
transmission from intermediate hosts [14, 20-27].  
The first outbreak of NiV infection occurred in the Malaysian peninsula and was a major 
epidemic of fatal viral encephalitis in people and respiratory and neurological illness in pigs from 
September 1998 to June 1999. The initial outbreak crippled the lucrative swine industry in 
Malaysia in less than a year. After the initial outbreak in Malaysia and Singapore, a second NiV 
outbreak in Bangladesh occurred in 2001 and the Indo-Bangladesh outbreaks have occurred 
nearly annually since then [15, 28]. In May 2018, the first NiV outbreak in southern India 
(Kerala) occurred in which there were 23 cases of NiV infection of which 21 resulted in death 
[6]. The Pteropus genus of large fruit bats have been identified as the natural reservoir of 
Henipaviruses and the known vector of NiV [29-31]. The transmission of NiV infection from 
bats to humans can occur via multiple routes; human ingestion of fresh date palm sap 
contaminated by the urine, saliva or feces of Pteropid bats; human or animal consumption of fruit 
partially eaten by the bat; or human contact with infected domestic animals [8, 14, 30].  
The characteristics of NiV that enhance the risk of this virus causing a global pandemic are 1) 
NiV is highly pathogenic to a broad range of mammals; 2) NiV is capable of person-to-person 
transmission; 3) high mortality rate associated with infection. A licensed vaccine or therapeutic 
is not available for NiV, even though NiV is classified as a Biological Safety Level 4 (BSL 4) 
pathogen, considered a pandemic threat and listed as a high priority pathogen for intervention 
development by the World Health Organization (WHO), Centers for Disease Control and 
Prevention (CDC), and the Coalition for Epidemic Preparedness Innovations (CEPI) [32].  
1.1 
Study Rationale  
 
Rationale for Development of NiV mRNA-1215 Vaccine 
ModernaTX, Inc. developed a rapid response, proprietary messenger RNA (mRNA)-based 
vaccine platform. This is based on the principle and observations that antigens can be produced 

 
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in vivo by delivery and uptake of the corresponding mRNA by cells. ModernaTX, Inc. in 
collaboration with the Vaccine Research Center (VRC) used its mRNA-based technology to 
develop a novel mRNA vaccine that encodes for the secreted prefusion stabilized F component 
covalently linked to G monomer (pre-F/G) of NiV, resulting in a post-expression trimerization.  
The VRC evaluated NiV vaccine antigen design options including the fusion glycoprotein (F) 
and the major attachment glycoprotein (G). A stabilized prefusion F (pre-F), multimeric G 
constructs, and chimeric proteins containing both pre-F and G were developed as protein subunit 
candidate vaccines. The proteins were evaluated for antigenicity and structural integrity using 
kinetic binding assays, electron microscopy, and other biophysical properties. 
Immunogenicity of the vaccine antigens was evaluated in mice. The stabilized pre-F 
trimer and hexameric G immunogens both induced serum neutralizing activity in mice, 
while the post-F trimer immunogen did not elicit neutralizing activity. The pre-F trimer 
covalently linked to G monomer (pre-F/G) induced potent neutralizing antibody activity and 
elicited responses to the greatest diversity of antigenic sites. The pre-F/G molecule is the lead 
candidate for clinical development [33, 34]. 
 
Rationale for mRNA-1215 Vaccine Dose and Regimen 
Phase 1 to 3 clinical trial data showed that SARS-CoV-2 mRNA vaccines administered at doses 
ranging from 25 mcg to 100 mcg were safe and well tolerated [35-38].  The mRNA-1215 
vaccine dose levels chosen to be clinically tested in this study are supported by published and 
available data of mRNA vaccines in humans as well as preclinical immunogenicity studies post 
administration of SARS-CoV-2 mRNA vaccines (Moderna, mRNA-1273 vaccine, and 
BNT162b2 vaccine, BioNTech/Pfizer) in mice and non-human primates (NHP). SARS-CoV-2 
specific antibodies were induced by doses ranging from 0.2-100 mcg [39-42]. Analyses of 
antibody responses elicited by different vaccine doses indicated that the mRNA vaccines induced 
a dose-dependent SARS-CoV-2-specific antibody response upon priming that was enhanced by a 
booster immunization [39-41, 43, 44]. The SARS-CoV-2 mRNA vaccines were able to 
neutralize the virus in vitro as measured by pseudovirus and SARS-CoV-2 neutralization assays, 
and antibody levels were sustained for two months or more post-immunization.  
A vaccination strategy to achieve protective immunity in most recipients with a single 
vaccination would be desirable in an outbreak setting.  Vaccination strategies that achieve 
durable protective immunity would be desirable for populations in areas of the world where 
outbreaks occur sporadically, and these strategies are to be further investigated in future studies 
in endemic populations.   
As indicated in the interim immunogenicity analysis for this study (Section 1.3.1), subjects in 
Groups 1-3 had a robust response to the vaccine and there was no significant difference in the 
binding or neutralizing antibody titers to pre-F or G proteins 2 weeks after the second dose 
between the dose groups. Therefore, the decision was made to test a lower dose of 10 mcg in 
Group 4 and use the same prime-boost interval of 4 weeks to enable a comparison between the 
doses (Section 4.6). 
 
 

 
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1.2 
Background  
1.2.1 Previous Human Experience with mRNA-based Vaccines 
This is the first clinical study to evaluate the mRNA-1215 vaccine, therefore there is no previous 
human experience with this investigational vaccine product prior to this trial.  
Two mRNA-based SARS-CoV-2 vaccines, Moderna’s mRNA-1273 vaccine and 
Pfizer/BioNTech’s BNT162b2 vaccine, both produce a stabilized version of the spike 
glycoprotein [45], show >94% efficacy against symptomatic COVID-19 in interim Phase 3 
analyses [35, 36], and are safe and effective. These vaccines are currently being administered to 
millions of people globally, and the most common adverse events are transient local and 
systemic reactions. Anaphylactic-like reactions have rarely occurred among recipients of mRNA 
COVID-19 vaccines. Myocarditis and pericarditis have been reported rarely following 
vaccination with mRNA COVID-19 Vaccines. These cases are generally mild, occurring a few 
days to up to a week after the vaccination and are more common after the second dose.  
1.2.2 
Preclinical Studies with mRNA-1215 Vaccine 
In a non-GLP rat immunogenicity study, mRNA-1215 was administered to Sprague Dawley rats 
via IM injection on Days 1 and 22 at levels of 30, 60, and 100 mcg/dose. Each dose level elicited 
strong binding and neutralizing antibodies in rats 13 days post-second dose (Day 35). mRNA-
1215 was well tolerated up to the high dose of 100 mcg/dose. There were no mRNA-1215 
related mortalities, changes in body weight or weight gain. Clinical observations, clinical 
chemistry, and transient injection site reactions were consistent with a mild-to-moderate 
inflammatory response, which is anticipated for a vaccine drug product.  
Refer to the Investigator’s Brochure for additional information on the pre-clinical studies with 
mRNA-1215. 
1.2.3 
Human Experience with mRNA-1215 Vaccine 
As of March 29, 2023, 30 subjects have been enrolled in Groups 1-3 of this study, completed the 
product administration schedule per protocol and remain active on the study. The first subject 
enrollment and study product administration occurred on July 11, 2022. The last Group 3 
enrollment occurred on December 27, 2022, and the last Group 3 study product administration 
occurred on January 24, 2023. No Serious Adverse Events (SAEs) occurred and no stopping or 
pausing rules were met at any time during this period. 
Data collection and monitoring are in progress at the time of this report, and the data can’t be 
considered final.  Of the 30 subjects enrolled, 28 (93.3%) reported at least one or more local 
solicited AEs with the maximum severity being severe for 1 (3.3%) subject, moderate for 1 
(3.3%) subject, and mild for 26 (86.7%) subjects. The most common local symptom was mild to 
moderate pain/tenderness at the injection site reported by 28 (93.3%) subjects, with one (3.3%) 
subject in Group 3 (100 mcg) reporting moderate and 27 (90.0%) subjects reporting mild 
severity.  
In Group 3 (100 mcg), one subject reported mild swelling (4.0 cm) and mild redness (4.5 cm)  
1 day after the second dose that resolved in 1 and 3 days, respectively. One subject reported 

 
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severe redness (10.5 cm) 2 days after the first dose, and mild redness (4.5 cm) 2 days after the 
boost, and both events resolved the same day.  
Two (6.7%) subjects, one in Group 1 (25 mcg) and one in Group 3 (100 mcg), reported mild 
pruritis after the second dose that resolved the same day. No axillary lymphadenopathy has been 
reported.  
All local solicited reactogenicity symptoms resolved within the 7-day reactogenicity collection 
period without residual effects except for one event of mild/pain tenderness which started one 
day after product administration and resolved 7 days after onset. 
Of the 30 subjects enrolled, 18 (60.0%) reported at least one or more systemic solicited AEs with 
the maximum severity being severe for 1 (3.3%) subject, moderate for 4 (13.3%) subjects, and 
mild for 13 (43.3%) subjects. The most common systemic symptom was mild to moderate 
malaise reported by 16 (53.3%) subjects, with two (6.7%) subjects in Group 3 (100 mcg) 
reporting moderate and 14 (46.7%) subjects reporting mild severity [2 in Group 1 (25 mcg), 6 
each in Group 2 (50 mcg) and Group 3 (100mcg)]. Headaches were reported by 14 (46.7%) 
subjects, with 1 (3.3%) subject in Group 2 (50 mcg) reporting moderate and 13 (43.3%) subjects 
reporting mild maximum severity (4 in Group 1, 3 in Group 2, and 6 in Group 3). Myalgia was 
reported by 11 (36.7%) subjects: 1 (3.3%) subject in Group 3 (100 mcg) reported moderate and 
10 (33.3%) reported mild severity (1 in Group 1, 4 in Group 2, and 5 in Group 3). Mild to 
moderate chills were reported by 6 (20.0%) subjects, with 3 (10.0%) reporting mild (1 in each 
group) and 3 (10.0%) in Group 3 (100 mcg) reporting moderate severity. Mild to moderate 
nausea was reported by 6 (20.0%) subjects, with 5 (16.7%) reporting mild (2 in Group 1, 2 in 
Group 2, and 1 in Group 3) and 1 (3.3%) in Group 3 (100 mcg) reporting moderate severity.  
Mild joint pain was reported by 5 (16.7%) subjects (1 in Group 1, 1 in Group 2, and 3 in Group 
3). An elevated temperature was reported by 2 (6.7%) subjects in Group 3 (100 mcg): 1 (3.3%) 
subject reported severe and 1 (3.3%) reported mild severity. The severe temperature elevation 
occurred in a Group 3 subject on the day of the 2nd study vaccination and resolved the same day. 
All solicited systemic reactogenicity symptoms resolved within the 7-day reactogenicity 
collection period without residual effects with the exception of malaise and headache events 
reported by 4 (13.3%) subjects: 1 (3.3%) Group 2 (50 mcg) subject reported malaise after the 2nd 
study vaccination that resolved 10 days after onset; 1 (3.3%) Group 2 (50 mcg) subject reported 
a headache of 8 day duration after the 1st study vaccination and headache and malaise of 7 day 
duration each that started one day after the 2nd study vaccination; two (6.7%) Group 3 (100 mcg) 
subjects reported malaise, 1 (3.3%) of 11 day duration after the 1st study vaccination, and 1 
(3.3%) of 1 day duration that started on day 7 after the 2nd study vaccination.  
Sixteen (16/30, 53.3%) subjects experienced one or more unsolicited AEs. The maximum 
severity was severe for one (3.3%), moderate for 7 (23.3%) and mild for 8 (26.7%) subjects. The 
most common unsolicited AE was anemia in 5 (16.7%) subjects. All events were evaluated as 
unrelated to study product and occurred most likely due to frequent blood draws required for this 
study. A severe (Grade 3) muscle strain occurred in a Group 2 (50 mcg) subject one day after the 
1st study vaccination. The subject was lifting heavy objects at work and was evaluated in the 
emergency room. This event was classified as a Medically Attended Adverse Event (MAAE) but 
was not an SAE or an Adverse Event of Special Interest (AESI), and it was evaluated as not 
related to study product. 

 
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Six (20.0%) subjects had the following events that were evaluated as related to study product: 
One (3.3%) Group 3 (100 mcg) subject had a moderate AE of dizziness after the 2nd vaccination 
while sitting and standing that interfered with usual activities and resolved 1 day after product 
administration. One (3.3%) Group 3 (100 mcg) subject developed a moderate urticarial rash 
occurring on the torso, extremities, hands and feet which began 12 days after the 1st study 
vaccination. Because the subject did not inform the study team about the hives at that time, the 
2nd study vaccine was administered and exacerbated the hives. This AE is ongoing, but 
significantly improved with sporadic hives treated as needed with antihistamines; it is classified 
as a MAAE and a new onset chronic medical condition. It was assessed as related to study 
product. 
One (3.3%) Group 3 (100 mcg) subject had mild hypertension 30 minutes after the 1st study 
vaccination that resolved 7 days after onset, and three (10.0%) subjects had mild leukopenia, 
which self-resolved without residual effects as noted below: 
• One Group 3 (100 mcg) subject had leukopenia (WBC 3.35 K/mcL) 7 days after the 2nd 
study vaccination that resolved 7 days after onset, 
• One Group 2 (50 mcg) subject had leukopenia (WBC 3.24 K/mcL) 7 days after the 1st 
study vaccination that resolved 7 days after onset, and 
• One Group 3 (100 mcg) subject had leukopenia (WBC 3.01 K/mcL; ALC 0.94 K/mcL) 7 
days after the 1st study vaccination that resolved 22 days after onset. 
No AESIs have been reported. 
Conclusions: Study product administrations were overall well tolerated.  No product related 
serious adverse events occurred.  Solicited local reactogenicity was predominantly mild 
pain/tenderness with similar frequencies between groups and after each dose. Solicited systemic 
reactogenicity occurred more frequently after the second dose and symptoms were experienced 
more frequently in the 100 mcg dose group. Solicited systemic events graded as moderate or 
severe occurred primarily in the 100 mcg dose group. All related, unsolicited events have 
resolved, except for urticaria in one participant in the 100 mcg dose group. 
Based on the data collected in this study so far, no safety concerns have emerged from the study 
of mRNA-1215 Nipah vaccine. 
1.3 
Laboratory Assessment of mRNA-1215 Vaccine Immunogenicity 
In this study, specimens to evaluate immunogenicity will be collected at baseline and at specified 
time points as indicated in APPENDIX I, Schedule of Evaluations. The primary immunogenicity 
time point is two weeks after last product administration. NiV-specific humoral immune 
responses will be assessed. Additional assessments of specific antibody responses may be 
conducted on stored samples obtained throughout the study. 
Exploratory evaluations may include the detection of antibodies (Ab) to NiV by neutralization 
and functional serological assays, and exploratory B and T cell assays. To support development 
of diagnostics, therapeutics and future vaccines, optional leukapheresis will be offered to 
subjects at two weeks post second vaccination.  

 
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Research samples will be processed by the Vaccine Immunology Program (VIP) in Gaithersburg, 
MD, which will also perform some of the immunogenicity assays. Some immunogenicity assays 
will be performed by the VRC laboratories in Bethesda, MD, or by approved contract 
laboratories or research collaborators. 
Results from this study are expected to contribute to the fund of knowledge needed for the 
development of a NiV mRNA vaccine candidate as well as to show proof-of-concept for safety 
and elicitation of antibody responses induced by a NiV mRNA vaccine.  
 
Interim Evaluation of the mRNA-1215 Vaccine Immunogenicity 
Serum samples collected at 2 weeks post boost (week 6, visit 07) were used for interim 
evaluation of vaccine immunogenicity to inform Group 4 dose selection. Responses to pre-F and 
mono-G were evaluated as described in Section 1.3. 
Subjects with evaluable samples (N=29) all had a robust response to the vaccine, and there was 
no significant difference in the binding antibody titers to pre-F or G proteins 2 weeks after the 
second dose between dose groups. Similarly, there were no differences in neutralizing antibody 
titers at this timepoint between the dose groups. 
In addition, immune responses at 12 weeks after the boost (week 16, visit 09) were evaluated. 
The binding and neutralizing antibody titers at week 16 have declined in comparison to the 
immune responses at week 6, however, no significant differences in the week 6 to week 16 
decline were found between the dose groups.  
 
 

 
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2. 
STUDY PRODUCTS 
2.1 
mRNA-1215 Vaccine 
The investigational mRNA-1215 vaccine is a lipid nanoparticle (LNP) dispersion that contains 
an mRNA encoding for the secreted prefusion stabilized trimeric F component covalently linked 
to G monomer (pre-F/G) of Malaysian strain NiV, resulting in a post-expression trimerization. It 
is provided as a sterile liquid for intramuscular (IM) injection, with white to off white dispersion 
in appearance. A pharmaceutical composition of the investigational product is described in 
Section 7.1. 
2.2 
Diluent: 0.9% NaCl for injection, USP 
0.9% NaCl for Injection, USP or normal saline is a sterile, nonpyrogenic, isotonic solution that 
will be used as a diluent to dilute the vaccine (mRNA-1215) to the desired concentration. 
 
 

 
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3. 
STUDY OBJECTIVES  
3.1 
Primary Objectives 
• To evaluate the safety and tolerability of a 2-dose vaccination regimen of mRNA-1215 at 
doses of 10 mcg, 25 mcg, 50 mcg or 100 mcg administered IM, given at a 4-week 
interval 
3.2 
Secondary Objectives  
• To evaluate antibody responses to the mRNA-1215 vaccine at doses of 10 mcg, 25 mcg, 
50 mcg or 100 mcg at 2 weeks after last product administration  
3.3 
Exploratory Objectives 
• To evaluate the specificity and functionality of mRNA-1215 vaccine-induced antibodies 
and the immune response in all study groups at various timepoints throughout the study 
• To evaluate the frequency, magnitude, phenotype, and specificity of B-cell, T-cell, and 
antibody responses at various time points throughout the study 
 

 
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4. 
SUBJECT POPULATION AND CLINICAL 
PROCEDURES 
4.1 
Overall Study Design 
This is a Phase I, dose escalation, open-label clinical trial to evaluate dose, safety, tolerability 
and immunogenicity of mRNA-1215 vaccine in healthy adults. The study schema is shown in 
Table 1. The hypotheses are that the vaccine is safe, tolerable and will induce an antibody 
response to the Nipah Virus (NiV). The study will be conducted by the VRC Clinical Trials 
Program at a single site (Vaccine Evaluation Clinic, VEC) at the NIH Clinical Center (NIH CC), 
Bethesda, MD.  
Table 1: VRC 322/DMID 21-0016 Study Schema 
Study Schema
Group
Subjects 
Dose/Route 
Day 0
Week 4
1 
10
25 mcg IM
X
X
2 
10
50 mcg IM
X
X
3 
10
100 mcg IM
X
X
4 
10
110 mcg IM
X
X
Total  
140  
1Enrollment up to 50 subjects is permitted in case additional 
evaluations are required for safety or immunogenicity. 
The study will have staged enrollment with required interim safety reviews, as described in 
Section 4.5, Criteria for Dose Escalation. The study opened with enrollments in Group 1. The 
dose for Group 4 was chosen based on interim analysis of safety and immunogenicity data from 
Groups 1-3 (Section 4.6). Subjects will be evaluated for safety and immune responses throughout 
the study for 52 weeks following last product administration. 
4.2 
Study Population 
All inclusion and exclusion criteria must be evaluated for eligibility.  
 
Inclusion Criteria 
A subject must meet all of the following criteria:  
1. Healthy adults between the ages of 18-60 years inclusive. 
2. Based on history and physical examination, in good general health and without history of 
any of the conditions listed in the exclusion criteria. 
3. Able and willing to complete the informed consent process. 
4. Available for clinic visits for 52 weeks after last product administration. 
5. Able to provide proof of identity to the satisfaction of the study clinician completing the 
enrollment process. 
6. Physical examination and laboratory results without clinically significant findings and a 
Body Mass Index (BMI) of 18 to 35 within the 56 days before enrollment. 

 
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Laboratory Criteria within 56 days before enrollment 
7. White blood cells (WBC) and differential within institutional normal range or 
accompanied by the site Principal Investigator (PI) or designee approval. 
8. Totallymphocytecount≥800cells/µL. 
9. Platelets = 125,000 – 500,000 cells/µL. 
10. Hemoglobin within institutional normal range or accompanied by the PI or designee 
approval. 
11. Alanine aminotransferase (ALT) ≤1.25xinstitutionalupperlimitofnormal(ULN). 
12. Aspartateaminotransferase(AST)≤1.25xinstitutional ULN. 
13. Alkaline phosphatase (ALP) <1.1 x institutional ULN. 
14. Total bilirubin within institutional normal range or accompanied by the PI or designee 
approval.  
15. Serumcreatinine≤1.1xinstitutionalULN. 
16. Negative for HIV infection by an FDA-approved method of detection  
Criteria applicable to women of childbearing potential: 
17. Negative beta-humanchorionicgonadotropin(β-HCG) pregnancy test (urine or serum) 
on the day of enrollment. 
18. Agrees to use an effective means of birth control from at least 21 days prior to enrollment 
through the end of the study. 
 
Exclusion Criteria 
A subject will be excluded if one or more of the following conditions apply:  
1. Breast-feeding or planning to become pregnant during the study.  
2. More than 10 days of systemic immunosuppressive medications or cytotoxic medications 
within the 4 weeks prior to enrollment or any within the 14 days prior to enrollment.  
3. Blood products within 16 weeks prior to enrollment. 
4. Any vaccine, including COVID-19 vaccines, received within 4 weeks prior to enrollment. 
5. Investigational research agents within 4 weeks prior to enrollment or planning to receive 
investigational products while on the study.  
6. Current allergy treatment with allergen immunotherapy with antigen injections, unless on 
maintenance schedule.  
7. Current anti-TB prophylaxis or therapy. 
8. Known immediate hypersensitivity to any component of the study product, including 
polyethylene glycol (PEG). 

 
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9. Confirmed past NiV infection, prior residence in (>6 months), or planned travel for any 
length of time during the study to countries where NiV infection is endemic, eg. 
Bangladesh, India, Philippines. 
Subject has a history of any of the following clinically significant conditions: 
10. Serious reactions to vaccines that preclude receipt of the study vaccination, including 
allergic reaction (anaphylaxis, urticaria or allergic reaction requiring medical 
intervention) to SARS-CoV-2 mRNA vaccines, as determined by the investigator  
11. History of myocarditis and/or pericarditis 
12. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema 
13. Asthma that is not well controlled  
14. Diabetes mellitus (type I or II), with the exception of gestational diabetes 
15. Thyroid disease that is not well controlled 
16. Idiopathic urticaria within the past year 
17. Autoimmune disease or immunodeficiency 
18. Hypertension that is not well controlled  
19. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet 
disorder requiring special precautions) or significant bruising or bleeding difficulties with 
IM injections or blood draws 
20. Malignancy that is active or history of malignancy that is likely to recur during the period 
of the study 
21. Seizure disorder other than 1) febrile seizures, 2) seizures secondary to alcohol 
withdrawal more than 3 years ago, or 3) seizures that have not required treatment within 
the last 3 years. 
22. Asplenia, functional asplenia or any condition resulting in the absence or removal of the 
spleen 
23. Guillain-Barré Syndrome 
24. Any medical, psychiatric, social condition, occupational reason or other responsibility 
that, in the judgment of the investigator, is a contraindication to protocol participation or 
impairs a subject’s ability to give informed consent, including but not limited to clinically 
significant forms of: infectious diseases, drug or alcohol abuse, autoimmune diseases, 
psychiatric disorders, or heart disease. 
4.3 
Inclusion of Vulnerable Subjects 
 
Pregnant Women 
This is a first-in-humantrialinhealthysubjects,≥18yearsofage.Because the effects of the 
vaccine on the fetus are not known, pregnant women will not be eligible for the trial. Women of 
childbearing potential must utilize a highly effective method of contraception and will be 

 
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required to have a negative urine or serum pregnancy test within 24 hours prior to each 
vaccination. 
 
Children 
Children are not eligible to participate in this clinical trial because the investigational vaccine has 
not been previously evaluated in adults. If the product is assessed as safe and immunogenic, 
other protocols designed for children may be conducted in the future. 
 
Adult Subjects who Lack the Capacity to Consent 
Adults who are unable to provide initial informed consent are excluded to enroll. Also, adults 
who permanently lose the capacity to provide on-going consent after initial consent and during 
the study will be discontinued from protocol participation as it is described in Section 4.7. 
 
NIH Employees 
NIH employees and members of their immediate families may participate in this protocol.  
Neither participation nor refusal to participate will have an effect, either beneficial or adverse, on 
the participant’s employment or work situation.  We will follow the Guidelines for the Inclusion 
of Employees in NIH Research Studies and will give each employee a copy of the “NIH FAQs 
for NIH Staff Who are Considering Participation in NIH Research” published by Office of 
Human Research Subjects Protections on Research Involving NIH Staff as Subjects, Policy 404.  
For NIH employee subjects, consent will be obtained by an individual who is independent of the 
employee’s team.   
If an NIH staff member seeks to enroll in research taking place within their own work unit or 
conducted by any of their supervisors, the employee will be:  
• 
Informed that neither participation nor refusal to participate as a research subject will 
have an effect, either beneficial or adverse, on the subject’s employment, training or 
position at the NIH,  
• 
When possible, consent should be obtained by an individual in a non-supervisory 
relationship with the subject, and  
• 
When consent is conducted, a third party (e.g. a consent monitor) will be included 
through the Bioethics Consultation Service or another party independent of the research 
team or, if a consent monitor is not available, the consent process will be observed by 
another qualified investigator on the study who is independent of the NIH staff member’s 
work unit and not a supervisor to the NIH staff member.  If no such person exists, 
consent observation may be performed by any qualified investigator on the 
study.  Protocol study staff will be trained on obtaining potentially sensitive and private 
information from co-workers or subordinates.   
4.4 
Clinical Procedures and Evaluation 
Evaluation of mRNA-1215 vaccine will include laboratory tests, medical history, physical 
assessment by clinicians, and subject self-assessment recorded on a diary card for 7 days after 

 
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injection. The schedule of study evaluations is described in this section and shown in table 
format in APPENDIX I. 
 
Recruitment and Retention Strategies  
Study enrollments will be conducted at the NIH Clinical Center. Study subjects will be recruited 
through the VRC’s screening protocol, VRC 500 (NCT 01375530). The on-site and off-site 
Institutional Review Board (IRB)-approved advertising will be implemented. Per a recruitment 
plan described in the VRC 500 protocol, efforts will be made to include women and minorities in 
proportions similar to that of the community from which they are recruited. 
 
Costs 
There are no costs to subjects for their participation in this trial.  
 
Compensation 
Subjects will be compensated for time and inconvenience in accordance with the standards for 
compensation of the NIH Clinical Research Volunteer Program. The compensation per visit will 
be $315 for the visits that include the administration of the study product and $200 for clinic 
visits that include a blood draw. The compensation for any clinic visit that does not include any 
specimen collection will be $85. The compensation for timely completion for all 7 days of the 
electronic diary card will be $25. Compensation will be $285 for apheresis, if performed. The 
total compensation for the subject is based on the number of study clinic visits completed, 
performance of optional research blood collections and timely submission of electronic diary 
cards.  
The total amount of compensation ($2,830 –$2,965) varies depending upon number and type of 
visits completed. Compensation may also vary depending upon participation in the optional 
apheresis and completion of electronic diary card. Subjects will usually receive compensation by 
direct deposit approximately 1 or 2 weeks after each completed visit. Compensation may need to 
be reported to the Internal Revenue Service (IRS) as taxable income. 
 
Screening 
All screening procedures for this study will be completed through the VRC’s screening protocol, 
VRC 500 (NIH 11-I-0164, NCT01375530) used for all VRC IND studies conducted at the NIH 
Clinical Center. The evaluations and sample collections included in screening are a medical 
history, physical exam, laboratory tests needed to confirm eligibility, HIV test, and pregnancy 
test for females of reproductive potential.  
If screening evaluations suggest a current concerning health condition or infection, then 
appropriate clinical laboratory tests may be conducted to evaluate these conditions under 
screening protocol, VRC 500. Additional assessments of health may be conducted during 
screening based on clinical judgment. Screening evaluations for specific eligibility criteria 
(Section 4.2) must be completed within the time interval specified prior to enrollment for the 
given parameter and may be repeated, as needed, to confirm eligibility. No screening procedures 
will be done under the protocol VRC 322/DMID-21-0016. 
Research blood samples as shown on the SoE may be collected at any time during screening.  

 
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Subjects who are not up to date on standard vaccinations may receive these, if available, during 
their participation in the screening protocol or at a later date during study participation. 
The informed consent form (ICF) will be reviewed and counseling related to pregnancy 
prevention will be provided. As part of the informed consent process, an Assessment of 
Understanding (AoU) will be completed in association with enrollment into VRC 322/DMID 21-
0016. Records will be kept documenting the reason if screened subjects do not enroll. 
 
Study Schedule  
The Schedule of Evaluations in APPENDIX I provides details on the study schedule, the 
permitted windows for completing the visits, and the evaluations to be performed at each visit. 
The visit schedule is based on intervals of time after study injection. The clinicians will discuss 
the target dates and timing of sample collections with each subject before completing enrollment 
to help ensure that subjects can comply with the projected schedule. 
After enrollment, deviations from the visit windows are discouraged and will be recorded as 
protocol deviations but are permitted at the discretion of the PI (or designee) in the interest of 
completing the vaccination schedule and obtaining subject safety and immunogenicity 
evaluations. 
If a participant undergoes a treatment with systemic glucocorticoids (e.g., prednisone or other 
glucocorticoid) or other immunomodulators (other than nonsteroidal anti-inflammatory drugs 
[NSAIDs]), study vaccination may continue per investigator discretion with the boost dose being 
preferably delayed to 2 weeks following completion of glucocorticoid treatment. This treatment 
will be documented as a concomitant medication and any delays in boost vaccinations recorded 
as a protocol deviation. 
Licensed or emergency use authorization (EUA) vaccines should be administered as needed, 
preferably within 4 weeks before or after each product administration. 
 
Enrollment and Day 0 
Day 0 is defined as the day of protocol enrollment and injection for all groups. Protocol-specific 
eligibility is reviewed on Day 0 as part of the enrollment process, but eligibility evaluations 
conducted during a screening visit are routinely used for eligibility if evaluations are within the 
specified window prior to Day 0 as it is described in the Schedule of Evaluations APPENDIX I. 
However, if clinical assessment on Day 0 suggests that significant changes have occurred since 
the screening visit, then evaluations done on Day 0 are used for eligibility. Day 0 evaluations and 
medical history prior to the injection are the baseline for subsequent safety assessments. 
The study group assignment in the database will be set up prior to opening the study to accrual. 
The group assignment is known to the staff and subject before completing the electronic 
enrollment into the study on Day 0. All subjects that receive mRNA-1215 will be expected to 
continue with follow-up through the end of the study. 
 
Birth Control and Pregnancy 
Women of reproductive potential must agree to the use of an effective method of birth control 
beginning 21 days prior to enrollment and continuing through end of study. 

 
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Acceptable and effective methods of birth control for women of reproductive potential in this 
study include abstinence (no sex) with male partners, birth control pills or patch, condoms, 
Medroxyprogesterone acetate (MPA) injection, diaphragm or cervical cap, intrauterine device 
(IUD), Implant (Nexplanon®), Annovera®, NuvaRing®, partner which has vasectomy.  
Pregnancy, if occurred, will be recorded in the study database. These participants will not receive 
any further study vaccinations and will not have any further research sample collections or 
procedures.   Pregnant participants will continue to be followed for clinical safety and to collect 
the pregnancy outcome. Any follow-up procedures and/or data collected will be for 
clinical/safety outcome purposes only. Pregnancy will be reported as described in Section 5.7. 
 
Vaccine Administration 
There are 2 study injections to be completed with a 4-week interval. All study injections will be 
completed according to the assigned group and will be administered IM in the deltoid muscle. 
Scheduled blood collection must be completed before vaccination. 
On the day of and prior to vaccine administration, study subjects will be clinically evaluated and 
samples will be collected as per Schedule of Evaluations APPENDIX I. A subject who arrives at 
the clinic with fever or evidence of an acute illness or injury that precludes administration of the 
vaccine may be rescheduled within the allowed study visit window. 
A negative pregnancy test result for women of reproductive potential must be obtained on the 
day of and prior to each vaccination. 
When choosing an arm for injection, clinicians will assess for injury, local skin conditions or 
tattoos that preclude administration or may interfere with evaluation of the injection site. The 
non-dominant arm is preferable. Prime and boost vaccinations should preferably be administered 
in the same arm. 
 
Post-Product Administration Follow-Up 
All subjects will be observed for a minimum of 30 minutes following each vaccination. Vital 
signs (temperature, blood pressure, pulse and respiratory rate) and assessment of local 
reactogenicity will be performed after product administration.  
In keeping with the NIH CC policy and good medical practice, acute medical care will be 
provided to subjects for any immediate allergic reactions or other injury resulting from 
participation in this research study.  
 
Solicited Adverse Events (Reactogenicity) 
Subjects will be given a “Diary Card” (paper and electronic-based available), a thermometer, and 
a measuring device. Subjects will use the diary card to record temperature, local and systemic 
symptoms, and concomitant medications daily for 7 days after each injection. Subjects will be 
provided training on diary completion and proper usage of the thermometer to measure 
temperature and the measuring device to measure injection site symptoms. While subjects will be 
encouraged to use the secure electronic database, they will have the option to complete a paper 
diary card. When the diary card parameters are recorded directly by the subject in the electronic 
database, the subject’s electronic record will be the source for these data. When collected on 
paper, the paper diary card will be the source document. When neither paper nor electronic diary 

 
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is available from the subject, the study clinician will document the source of reactogenicity 
information recorded in the study database. 
The solicited reactogenicity signs and symptoms on the diary card will include the following 
systemic symptoms: generalized symptoms of unusually tired/feeling unwell, fever, muscle 
aches (other than at injection site), headache, chills, nausea, and joint pain. The following local 
reactogenicity symptoms will be included: pain/tenderness, redness, swelling, and pruritus at the 
injection site, and axillary lymphadenopathy ipsilateral to the injection site.  
Each day, subjects will also record their highest measured temperature and measurement of the 
largest diameter of redness and swelling, and highest severity of pruritus at the injection site.  
Follow-up on subject well-being will be performed by telephone on the first or second day 
following vaccination and by clinic visits as shown in the Schedule of Evaluations (APPENDIX 
I). Subject diaries will be reviewed by a clinician for accuracy and completeness at follow-up 
visits.  
Events following product administration that may require clinical evaluation include but are not 
limited to rash,urticaria,feverof38.5˚C(Grade2) or higher lasting greater than 24 hours, or 
significant impairment in the activities of daily living. Additionally, other clinical concerns may 
prompt a study visit based on the judgment of a study clinician. 
The following attributes of the solicited AE(s) will be captured in the study database: 
• Solicited local or systemic AE that results in a visit to a healthcare practitioner 
• Solicited local or systemic AE leading to the participant withdrawing from the study 
or the participant being withdrawn from the study by the Investigator (AE leading to 
withdrawal) 
• Solicited local or systemic reactogenicity lasting beyond 7 days after injection 
• Solicited local or systemic reactogenicity that otherwise meets the definition of an SAE 
 
Follow-up through End of Study 
Study follow-up will continue via clinic visits through 52 weeks following the vaccine 
administration. Refer to Section 4.7 which describes the criteria for discontinuing study 
participation. 
 
Blood Sample Collection 
At intervals throughout the study, blood will be drawn for safety and immunologic assays. Blood 
will be drawn from the arm veins of subjects by standard phlebotomy procedures. The order of 
blood sample collections is shown in the SoE (APPENDIX I), with samples for safety and 
primary immunogenicity evaluations collected first, and other research samples as permitted with 
adequate supplies. Total blood volume drawn from each subject will not exceed the NIH CC 
guidelines.  
 
Apheresis 

 
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Subjects will be offered apheresis as an optional procedure at Visit 07. Apheresis is done in order 
to collect blood cells of special interest for research purposes. The apheresis procedure will be 
carried out by trained NIH Department of Transfusion Medicine (DTM) medical staff using 
automated cell separator devices. All study subjects will be treated according to standard DTM 
whole blood and apheresis donation policies and procedures. Prior to the scheduling apheresis, 
the subject must have a venous assessment performed by the DTM staff.  
In order to undergo apheresis procedures, a subject must meet the apheresis eligibility criteria as 
described in Section 4.4.14 and have no medical contraindications, as determined by the DTM 
staff. A VRC study clinician will complete a checklist for apheresis eligibility before referring a 
subject for the procedure. 
Prior to beginning the apheresis procedure, a study clinician may request in advance that other 
laboratory samples be collected as needed to monitor the well-being of the subject or if needed 
by a research laboratory. In addition, for women of reproductive potential, a pregnancy test by 
blood or urine will be performed by a VRC study clinician within 72 hours prior to the apheresis 
procedure. Results must be negative to proceed with apheresis. 
The Dowling Apheresis Clinic staff at the NIH CC routinely performs a hemoglobin test prior to 
initiating apheresis, per DTM Apheresis Clinic standard policies. If a subject is found to have a 
hemoglobin value less than permitted by the Apheresis Clinic, then the apheresis will not be 
initiated, and the ordering provider will be notified.  
In this study, the procedure will require two antecubital venous access sites and will involve 
processing 1 to 4 liters of whole blood. The expected mononuclear cell yield is approximately 
0.5 to 1.0 x 109 cells per liter processed, and the apheresis device can process about 2 to 3 liters 
per hour. Thus, 1 to 2 hours are required to process 1 to 4 liters of blood and obtain about 1 to 4 
x 109 leukocytes. The packed red cell loss during the procedure is the equivalent of a 6 mL blood 
draw; this is the volume that will be used for the purposes of calculating cumulative blood draw 
when apheresis is performed. 
During or following an apheresis visit, if there is any concern about the well-being of the subject, 
the DTM clinic may conduct appropriate medical evaluations by history-taking, physical 
examination, laboratory tests, and/or other testing. 
 
Apheresis Eligibility Criteria 
Subject must meet all of the following criteria:  
• Afebrile (temperature < 37.5°C) 
• Weight≥110pounds 
• Adequate bilateral antecubital venous access 
• Hemoglobin > 12.5 g/dL for females; > 13.0 g/dL for men 
• Platelets > 150,000 cells/µL 
• No cardiovascular instability as indicated by: a) history of medically significant cardiac 
arrhythmia within the last 12 months, or b) ischemic cardiovascular disease within the 
last 12 months, or c) heart rate outside of the 50 - 100 beats/minute interval (on 3 

 
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successive readings), or d) blood pressure greater than 180 mmHg (systolic) or 100 
mmHg (diastolic) on 3 successive readings 
• No current lung or kidney disease  
• No known coagulation disorder 
• No sickle cell disease  
• No active or chronic hepatitis  
• No intravenous injection drug use in the past 5 years  
• Not breast feeding 
• Negative beta-humanchorionicgonadotropin(β-HCG) pregnancy test (urine or serum) 
performed by a VRC study clinician within 72 hours prior to the apheresis procedure for 
those women with childbearing potential.  
 
Concomitant Medications 
Information about prior and current medications starting 4 weeks prior to enrollment will be 
collected in the appropriate data collection form. Routine prescription medications in use at the 
time of enrollment will be entered in the database. Subsequently, the concomitant medications 
that will be recorded or updated in the database are those associated with an AE requiring 
expedited reporting or the development of a new chronic condition requiring ongoing medical 
management. Inclusion of other concomitant medications in the database may also be determined 
at the discretion of the PI. Otherwise, concomitant medications that include all medications 
(prescription, over the counter, and supplements) taken throughout the study will be recorded in 
the subject’s study chart and general medical record but will not be recorded in the database. At 
each study visit following dosing, including telephone calls, subjects will be queried about new 
concomitant medications and changes to existing medications. 
A treatment with systemic glucocorticoids (e.g., prednisone or other glucocorticoid) or other 
immunomodulators (other than nonsteroidal anti-inflammatory drugs [NSAIDs]) will be 
recorded in the study database as described in Section 4.4.5. 
Receipt of an FDA-approved vaccine at any time during the study will be recorded in the 
database (clinicians should work with subjects regarding the timing of licensed vaccines relative 
to study injections, as described in Section 4.4.5). 
4.5 
Criteria for Dose Escalation 
There will be two interim safety data reviews in this study to evaluate safety data for a dose 
escalation of mRNA-1215 from a 25 mcg dose (Group 1) to a 50 mcg dose (Group 2), and from 
a 50 mcg to a 100 mcg dose (Group 3). The Protocol Safety Review Team (PSRT) will conduct 
an interim safety data review before dose escalation may occur. The PSRT must assess the data 
as showing no significant safety concerns before enrollment of the next dose level may proceed. 
Enrollment will begin in Group 1 (25 mcg IM mRNA-1215) with no more than one subject 
enrolled per day for the first three subjects. When the two weeks post initial vaccination visit for 
at least 3 subjects in Group 1 is completed, there will be an interim safety review of available 

 
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data to determine whether to proceed with the dose escalation to the 50 mcg dose of mRNA-
1215.  
If the 25 mcg IM dose of mRNA-1215 is assessed as safe, enrollment will begin for Group 2 (50 
mcg IM mRNA-1215) with no more than one subject enrolled per day for the first three subjects 
only. When the two weeks post initial vaccination visit for at least 3 subjects in Group 2 is 
completed, there will be an interim safety review of available data to determine whether to 
proceed with the dose escalation to the 100 mcg dose of mRNA-1215 (Group 3).  
Consultation with the IRB and FDA, if needed, as per study pause criteria (Section 4.7) will 
occur if indicated by the review. One outcome of a dose escalation review may be to recommend 
evaluation of additional subjects at the current dose level and reassess for safety before 
proceeding to a higher dose level and repeat dosing at the same dose level. 
4.6 
Group 4 Dose Selection 
The Group 4 vaccine dose was selected based on safety and immunogenicity data collected for 
Groups 1, 2 and 3. Interim safety data collected during the study (Section 1.2.3) and available 
data on immune responses at 2 and 12 weeks post last vaccination have been reviewed (Section 
1.3.1). Additional data collected in other mRNA-based vaccine studies were taken into 
consideration. The IND Sponsor and the vaccine manufacturer participated in the Group 4 dose 
selection. 
Based on the interim data analysis, the decision was made to use a lower dose of 10 mcg in 
Group 4 with a prime-boost interval of 4 weeks to enable a comparison between the doses.  If the 
lower dose regimen results in acceptable safety and immunogenicity, this regimen may impact 
the design of future trials that would be conducted in an endemic country where Nipah virus 
outbreaks occur. 
4.7 
Criteria for Discontinuing Protocol Participation 
All subjects will be encouraged to remain in the study and to continue follow-up visits to 
evaluate safety. A subject may be discontinued from protocol participation by the PI or designee 
for the following reasons: 
• Subject voluntarily withdraws 
• Subject develops a medical condition that is a contraindication to continuing study 
participation 
• The IND Sponsor or regulatory authority stops the protocol 
• The IND Sponsor or PI assesses that is it not in the best interest of the subject to continue 
participation in the study or that the subject’s compliance with the study is not sufficient. 
4.8 
Discontinuing Second Vaccination 
The PI or designee may also determine that there is a contraindication for administration of the 
second study vaccination. Subjects who do not get the second injection per protocol will have an 

 
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adjusted follow-up schedule and will be asked to continue the study visits and follow-up for 
safety. 
Specific events that will require withdrawal of a subject from the injection schedule include: 
1. Pregnancy 
2. Grade 2 adverse event assessed as related to a study injection that does not resolve 
to baseline in time for the next scheduled immunization 
3. Grade 3 adverse event assessed as related to a study injection (with the exception 
that self-limited Grade 3 solicited reactogenicity does not require discontinuation 
of study injections) 
4. Grade 4 adverse event assessed as related to a study injection 
5. Immediate hypersensitivity reaction associated with a study injection 
6. Intercurrent illness that is not expected to resolve prior to the next scheduled study 
injection assessed by study clinician to require withdrawal from the injection 
schedule  
7. Repeated failure of participant to comply with protocol requirements 
8. The study PI assesses that it is not in the best interest of the subject to continue on 
the vaccination schedule.   
4.9 
Criteria for Pausing and Resuming the Study  
 
Plan for Pausing the Study 
The PI and Protocol Safety Review Team (PSRT) will closely monitor and analyze study data as 
it becomes available and will make determinations regarding the presence and severity of AEs. 
The administration of study injections and new enrollments will be paused and the IND Sponsor 
will be promptly notified according to the following criteria: 
• One (or more) subject experiences a SAE or Grade 4 AE assessed as related to the 
vaccine. 
• One (or more) subject experiences ulceration, abscess or necrosis at the injection site 
assessed as related to the vaccine. 
• One (or more) subject experiences laryngospasm, bronchospasm, or anaphylaxis assessed 
as related to the vaccine. 
• One (or more) subject experiences myocarditis or pericarditis.  
• Two (2) or more subjects experience an allergic reaction such as generalized urticaria 
(defined as occurring at three or more body parts) assessed as related to the vaccine. 
• Three (3) or more subjects experience a Grade 3 AE (unsolicited and/or clinical 
laboratory abnormality), in the same Preferred Terms based on the medical dictionary for 
regulatory activities (MedDRA) coding, assessed as related to the vaccine.  
 

 
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Plan for Review of Pauses and Resuming the Study 
The IND Sponsor, with participation of the Safety Monitoring Committee (SMC, Section 8.7.2), 
study PI, PSRT, and vaccine manufacturer, will conduct the review and make the decision to 
resume, amend or close the study and notify the IRB and the FDA accordingly. As part of the 
pause review, the reviewers will also advise on whether the study needs to be paused again for 
any subsequent AEs of the same type. The pause criterion for SAEs will continue to apply. 
The administration of study injections and new enrollments would resume only if review of the 
events that caused the pause resulted in a recommendation to permit further enrollments and 
study injections. Safety data reports and changes in study status will be submitted to relevant 
regulatory authorities in accordance with Section 5.0 and institutional policy.

 
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5. 
SAFETY AND ADVERSE EVENT REPORTING 
5.1 
Adverse Events 
Adverse Event (AE) - Any untoward medical occurrence in a human subject, including any 
abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or 
disease, temporally associated with the subject’s participation in research, whether or not 
considered related to the subject’s participation in the research. In the context of FDA-required 
reporting, an AE means any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. All AEs, including laboratory abnormalities, 
will be followed to resolution or stabilization. 
Each AE will be graded according to the Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, Food and Drug 
Administration Guidance – September 2007, APPENDIX II. The following guidelines will be 
used to determine whether or not an AE is recorded in the study database: 
1. Solicited AEs (i.e., reactogenicity parameters as defined in Section 4.4.10) will be 
recorded without attribution assessments by the subject on paper or an electronic diary 
card for 7 days after each injection. If the paper diary card is completed by a subject, data 
will be transcribed by a clinician into the study database. Clinicians will follow and 
collect resolution information for any reactogenicity symptoms that are not resolved 
within 7 days. 
2. Unsolicited AEs will be recorded with assessments of relatedness to study product, 
severity and seriousness (per Section 5) by the investigator in the study database from 
receipt of the study injection through completion of the 4-week post-product 
administration visit. After that through the last study visit, only SAEs (Section 5.2), 
adverse events of special interest (AESI, Section 5.4), AEs leading to withdrawal, and 
new onset chronic medical conditions will be recorded.  
3. Medically attended AEs (MAAEs, Section 5.5) will be collected through 6 months after 
the last vaccination. 
5.2 
Serious Adverse Events 
The term “Serious Adverse Event” (SAE) is defined in 21 CFR 312.32 as follows: “An adverse 
event or suspected adverse reaction is considered serious if, in the view of either the investigator 
or the sponsor, it results in any of the following outcomes: Death, a life-threatening adverse 
event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or 
significant incapacity or substantial disruption of the ability to conduct normal life functions, or a 
congenital anomaly/birth defect. Important medical events that may not result in death, be life-
threatening, or require hospitalization may be considered serious when, based upon appropriate 
medical judgment, they may jeopardize the patient or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an emergency 
room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, 
or the development of drug dependency or drug abuse.” 

 
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“Life threatening” refers to an AE or suspected adverse reaction that represents an immediate 
risk of death to the subject. It does not include an AE or suspected adverse reaction that, had it 
occurred in a more severe form, might have caused death. Similarly, a hospital admission for an 
elective procedure is not considered a SAE. 
5.3 
Adverse Event Reporting to the IND Sponsor 
AEs that meet SAE criteria must be reported and submitted by the clinical site on an expedited 
basis to the IND Sponsor, DMID, according to sponsor guidelines as follows: 
• Results in death, 
• Is life threatening (places the subject at immediate risk of death from the event as it 
occurred), 
• Results in inpatient hospitalization or prolongation of existing hospitalization, 
• Results in a persistent or significant disability/incapacity, 
• Results in a congenital anomaly/birth defect in the offspring of a study subject, OR 
• Based upon appropriate medical judgment, may jeopardize the subject’s health and may 
require medical or surgical intervention to prevent one of the other outcomes listed in this 
definition (examples of such events include allergic bronchospasm requiring intensive 
treatment in the emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug abuse). 
• In addition, any event, regardless of severity, which in the judgment of an investigator 
represents a SAE, may be reported on an expedited basis. 
An investigator will communicate an initial SAE report within 24 hours of site awareness of 
occurrence to the IND Sponsor by data entry into the database, which triggers an alert to the IND 
Sponsor Medical Officer (DMID Medical Monitor) and DMID Pharmacovigilance (Section 5.6). 
Within 3 working days, a written summary by the investigator should be submitted to the IND 
Sponsor. 
In order for the IND Sponsor to comply with regulations mandating sponsor notification of 
specified SAEs to the FDA within 7 and/or 15 calendar days, the investigator must submit 
additional information as soon as it is available. 
5.4 
Adverse Events of Special Interest (AESI) 
An AESI is an AE (serious or nonserious) of scientific medical concern specific to the Sponsor’s 
product or program, for which ongoing monitoring and immediate notification by the 
investigator to the Sponsor is required. Such events may require further investigation to 
characterize and understand them. A list of additional AESI that should be prospectively 
collected is included in APPENDIX III. AESIs are collected through the entire study period and 
recorded in the database. AESIs that are also SAEs must be reported to the Sponsor or designee 
within 24 hours of site awareness of the event via the electronic data capture (EDC) system. The 
investigator will continue to submit any updated information on AESIs that are SAEs to the 
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Anaphylaxis  
All suspected cases of anaphylaxis should be recorded as AESIs and reported as SAEs. For 
reporting purposes, a participant who displays signs/symptoms consistent with anaphylaxis as 
shown below should be reported as a potential case of anaphylaxis. This is provided as a general 
guidance for investigators and is based on the Brighton Collaboration case definition [46]. 
Anaphylaxis is an acute hypersensitivity reaction with multi organ system involvement that can 
present as, or rapidly progress to, a severe life-threatening reaction. It may occur following 
exposure to allergens from a variety of sources. Anaphylaxis is a clinical syndrome characterized 
by:  
• Sudden onset AND 
• Rapid progression of signs and symptoms AND 
• Involving 2 or more organ systems, as follows: 
o Skin/mucosal: urticaria (hives), generalized erythema, angioedema, generalized 
pruritus with skin rash, generalized prickle sensation, red and itchy eyes 
o Cardiovascular: measured hypotension, clinical diagnosis of uncompensated 
shock, loss of consciousness or decreased level of consciousness, evidence of 
reduced peripheral circulation 
o Respiratory: bilateral wheeze (bronchospasm), difficulty breathing, stridor, upper 
airway swelling (lip, tongue, throat, uvula, or larynx), respiratory distress, 
persistent dry cough, hoarse voice, sensation of throat closure, sneezing, 
rhinorrhea 
o Gastrointestinal: diarrhea, abdominal pain, nausea, vomiting 
 
Myocarditis and Pericarditis  
A case of suspected, probable, or confirmed myocarditis, pericarditis, or myopericarditis should 
be reported as an AESI, even if it does not meet criteria per the CDC case definition (see 
APPENDIX III) [47, 48].  The event should also be reported as an SAE if it meets seriousness 
criteria (Section 5.2).  
5.5 
Medically Attended Adverse Events (MAAEs) 
MAAEs are defined as adverse events leading to hospitalization, an emergency room visit or an 
otherwise unscheduled visit to or from medical personnel, for any reason. The MAAEs will be 
collected and recorded in the database in a period from the first vaccination to 6 months after the 
last vaccination. 
5.6 
Reporting of Serious Adverse Events to DMID Pharmacovigilance  
SAEs will be followed until resolution even if this extends beyond the study-reporting period.  
Resolution of an AE is defined as the return to pretreatment status or stabilization of the 
condition with the expectation that it will remain chronic.  

 
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Any AE that meets a protocol-defined serious criterion must be submitted immediately (within 
24 hours of site awareness) on an SAE form to the DMID Pharmacovigilance Group, at the 
following address: 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Dr. Suite 650 
Bethesda, MD 20817, USA 
SAE Hot Line: 1-800-537-9979 (US) or 1-301-897-1709 (outside US) 
SAE FAX Number: 1-800-275-7619 (US) or 1-301-897-1710 (outside US) 
SAE Email Address: PVG@dmidcroms.com 
Other supporting documentation of the event may be requested by the DMID Pharmacovigilance 
Group and should be provided as soon as possible.  
In addition to the VRC notification, the DMID Medical Monitor and DMID Clinical Project 
Manager will be informed of the SAE by the DMID Pharmacovigilance Group.  The DMID 
Medical Monitor will review and assess the SAE for regulatory reporting and potential impact on 
study subject safety and protocol conduct. 
At any time after completion of the study, if the site principal investigator or appropriate sub-
investigator becomes aware of an SAE that is suspected to be related to study product, the site 
principal investigator or appropriate sub-investigator will report the event to the DMID 
Pharmacovigilance Group. 
5.7 
Reporting of Pregnancy 
Pregnancy is not an adverse event, but pregnancy, if occurred, will be recorded in the study 
database, and subjects will be followed for clinical safety and to collect the pregnancy outcome 
as described in Section 4.4.7. Pregnancy itself is not regarded as an SAE. However, congenital 
abnormalities or birth defects and spontaneous miscarriages that meet serious criteria (Section 
5.2) should be reported as SAEs. 
Pregnancy, if occurred, will be reported to the Sponsor no later than 24 hours after investigator 
awareness. The Investigator will notify the Sponsor no later than 24 hours of when the outcome 
of the pregnancy becomes known.  
Pregnancy will be reported to regulatory agencies.   
5.8 
IND Sponsor Reporting to the FDA  
The IND Sponsor is responsible for making the determination of which SAEs are “serious and 
unexpected suspected adverse reactions” (SUSARs) as defined in 21 CFR 312.32. The following 
definitions apply: 
• Suspected Adverse Reaction means any AE for which there is a reasonable possibility 
that the drug caused the AE.  

 
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• Unexpected Adverse Event means an AE that is not listed (refer to Risks in Section 8.5) at 
the specificity or severity that has been observed.  
All SUSARs (as determined by the IND Sponsor) will be reported to the FDA as IND Safety 
Reports per 21 CFR 312.32 as soon as possible but not exceeding 7 calendar days for unexpected 
fatal or life-threatening events, and not exceeding 15 calendar days for other qualifying events. 
IND Safety Reports will also be provided to the IRB.  
The IND Sponsor will also submit an IND Annual Report of the progress of the investigation to 
the FDA as defined in 21 CFR 312.33. 
5.9 
Reporting to the Institutional Review Board 
The following information is consistent with NIH IRB Policy 801: Reporting Research Events.  
Reportable Event - An event that occurs during the course of human subject research that 
requires notification to the IRB. 
For the purposes of this policy, reportable events include the following: 
• Unanticipated Problems (UPs) involving risks to subjects or others 
• Non-compliance (including major protocol deviations and noncompliance that is not 
related to a protocol deviation) 
• Deaths related or possibly related to research activities 
• New information that might affect the willingness of subjects to enroll or continue 
participation in the study 
• Suspension or termination of research activities 
 
Unanticipated Problem 
An Unanticipated Problem (UP) is defined as any incident, experience, or outcome that meets all 
the following criteria: 
• Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB approved research 
protocol and informed consent document; and (b) the characteristics of the subject 
population being studied; and 
• Related or possibly related to participation in the research (possibly related means there is 
a reasonable possibility that the incident, experience, or outcome may have been caused 
by the procedures involved in the research); and 
• Suggests that the research places subjects, or others (which may include research staff, 
family members or other individuals not directly participating in the research) at a greater 
risk of harm (including physical, psychological, economic, or social harm) related to the 
research than was previously known or expected. 
A UP must be reported within 7 calendar days of an investigator becoming aware of the actual or 
suspected UP. 

 
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Non-Compliance 
Non-compliance is the failure of investigator(s) to follow the applicable laws, regulations, or 
institutional policies governing the protection of human subjects in research, or the requirements 
or determinations of the IRB, whether intentional or not. 
Non-compliance may be unintentional (e.g. due to lack of understanding, knowledge, or 
commitment), or intentional (e.g. due to deliberate choice to ignore or compromise the 
requirements of any applicable regulation, organizational policy, or determination of the IRB). 
Non-compliance is further characterized as serious or continuing as follows: 
• Serious non-compliance – Non-compliance, whether intentional or not, that results in 
harm or otherwise materially compromises the rights, welfare and/or safety of the subject. 
Non-compliance that materially effects the scientific integrity or validity of the research 
may be considered serious non-compliance, even if it does not result in direct harm to 
research subjects. 
• Continuing non-compliance – A pattern of recurring non-compliance that either has 
resulted, or, if continued, may result in harm to subjects or otherwise materially 
compromise the rights, welfare and/or safety of subjects, affect the scientific integrity of 
the study or validity of the results. The pattern may comprise repetition of the same non-
compliant action(s), or different noncompliant events. 
Any actual or suspected non-compliance by any investigator or entity associated with the 
protocol must be reported to the IRB by the PI/designee within 7 calendar days of any 
investigator or individual associated with the protocol first becoming aware. 
 
Protocol Deviation 
A Protocol Deviation (PD) is defined as any change, divergence, or departure from the IRB-
approved research protocol and are further characterized as major and minor as follows:  
• Major Deviations – Deviations from the IRB approved protocol that have, or may have 
the potential to, negatively impact, the rights, welfare or safety of the subject, or to 
substantially negatively impact the scientific integrity or validity of the study.  
• Minor Deviations – Deviations that do not have the potential to negatively impact the 
rights, safety, or welfare of subjects or others, or the scientific integrity or validity of the 
study. 
For the reporting purposes, failure of subjects to comply with the research protocol does not 
represent non-compliance unless that failure is due to an action or omission of a member of the 
research team, for example, the failure to give adequate instruction to the subject. 
A major deviation must be reported within 7 calendar days of an investigator becoming aware of 
an actual or suspected deviation. Although PDs are also non-compliance, these should only be 
reported once as deviations. Major deviations resulting in death must be reported within 24 hours 
of the occurrence of the event or of any member of the study team becoming aware of the death. 
Researchers are responsible for monitoring their studies throughout the year for adherence to the 
IRB approved protocol. The purpose of this monitoring is to identify major deviations and to 

 
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look for trends in minor deviations that may indicate a systemic issue in how the study is being 
conducted that could potentially negatively impact the rights, safety, or welfare of participants or 
the study’s ability to produce scientifically valid results. A series of minor deviations pointing 
toward a more global issue that could affect the rights, safety or welfare of the participant or 
affect the validity of the study should be reported as a major deviation. In all other instances, a 
summary of minor deviations should be provided to the IRB at the time of continuing review. 
 
Death 
Any death of a research subject that is possibly, probably or definitely related to the research 
must be reported within 24 hours of an investigator becoming aware of the death. 
 
New Information 
New information that might affect the willingness of a subject to enroll or remain in the study 
should be reported within 7 calendar days of an investigator first becoming aware. 
 
Suspension or Termination of Research Activities 
Any suspension or termination of research activities, including holds on new enrollment, placed 
upon the research by the study sponsor, NIH or IC leadership, or any regulatory agency must be 
reported within 7 calendar days of an investigator becoming aware. 
 
Expedited Reporting to the IRB 
Death related to research must be reported within 24 hours. 
The following will be reported within 7 calendar days of investigator awareness:  
• Actual or suspected UPs, 
• Actual or suspected non-compliance, 
• Actual or suspected Major PDs, 
• SAEs that are actual or suspected UPs, 
• New information that might affect the willingness of a subject to enroll or remain in the 
study, 
• Suspension or termination of research activities, including holds on new enrollment, 
placed upon the research by the study sponsor, NIH or IC leadership, or any regulatory 
agency. 
 
Annual Reporting to the IRB 
The following will be reported to the IRB in summary at the time of Continuing Review: 
• Summary of UPs and non-compliance, 
• AEs, including SAEs, that are not UPs, as a narrative summary statement indicating 
whether these events were within the expected range, 
• Minor PDs (aggregate summary), 
• Any trends or events which in the opinion of the investigator should be reported. 

 
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6. 
STATISTICAL CONSIDERATIONS 
6.1 
Overview 
This is a Phase I, dose escalation, open-label clinical trial to evaluate dose, safety, tolerability 
and immunogenicity of a NiV mRNA vaccine, mRNA-1215. 
6.2 
Sample Size and Accrual 
Recruitment will target 40 healthy adult participants between 18 to 60 years of age. Up to 50 
participants may be enrolled if deemed necessary for safety or immunogenicity evaluations. Each 
study group will recruit 10 healthy subjects.  
6.3 
Endpoints 
 
Primary Endpoints: Safety 
Assessment of product safety will include clinical observation and monitoring of hematological 
and chemical parameters. APPENDIX I provides details and specified time points for medical 
assessments. The following endpoints will be assessed for all study groups: 
• Frequency and severity of solicited local reactogenicity symptoms reported for 7 days 
after each product administration 
• Frequency and severity of solicited systemic reactogenicity symptoms reported for 7 
days after each product administration 
• Frequency and grade of any unsolicited AEs, including abnormal safety laboratory 
measures, during the 28-day follow-up period post each vaccination 
• Frequency of serious adverse events (SAEs), AESIs, adverse events leading to 
withdrawal, and new chronic medical conditions through the last study visit 
• Frequency of MAAEs through 6 months after last vaccination 
 
Secondary Endpoints: Immunogenicity 
Secondary objectives will evaluate binding antibody responses to the mRNA-1215 vaccine (pre-
F and G proteins) at doses of 10 mcg, 25 mcg, 50 mcg and 100 mcg at 2 weeks after last product 
administration as follows: 
• Geometric Mean Titer (GMT) with 95% CI for the NiV-specific antibodies will be 
reported for study groups as appropriate.  
 
Exploratory Endpoints: Immunogenicity  
Exploratory endpoints may evaluate the specificity and functionality of mRNA-1215 vaccine-
induced antibodies and the immune response at various timepoints throughout the study. 
Additionally, exploratory endpoints may also evaluate the frequency, magnitude, phenotype, and 
specificity of B-cell, T-cell, and antibody responses at various time points throughout the study. 
 
Sample Size Consideration for Safety 

 
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For each group (dose escalation) with sample size n=10, there is over 90% chance to observe at 
least 1 SAE if the true rate is at least 0.21 and over 90% chance to observe no SAE if the true 
rate is no more than 0.01. Probabilities of observing 0 or more than 1 SAE within a group are 
presented in Table 2 for a range of possible true event rates. 
Table 2: Probability of Observing Events under Different Scenarios within a Group (n=10)  
True Event 
Rate 
Groups 1-4, n=10 
Pr(0) 
Pr(>1) 
0.005 
0.951 
0.001 
0.01 
0.904 
0.004 
0.02 
0.817 
0.016 
0.03 
0.737 
0.035 
0.04 
0.665 
0.058 
0.05 
0.599 
0.086 
0.1 
0.349 
0.264 
0.15 
0.197 
0.456 
0.2 
0.107 
0.624 
0.3 
0.028 
0.851 
0.4 
0.006 
0.954 
0.5 
0.001 
0.989 
Table 3 gives the upper and lower bounds for 95% exact binomial confidence intervals of the 
true SAE rate at possible numbers of events within a group.  Within a group of size n=10, if none 
experience an SAE, the 95% exact confidence interval has upper bound 0.308. Within a group of 
size n=10, if 2 enrollees experience an SAE, the exact 95% confidence interval has lower bound 
0.025 and upper bound 0.556. 
Table 3: 95% Confidence Intervals for True Rate under Possible Observed Number of 
Events 
Observed Number 
of Events 
95% Confidence Interval 
(n=10) 
Lower Bound 
Upper Bound 
0 
0.000 
0.308 
1 
0.003 
0.445 
2 
0.025 
0.556 
3 
0.067 
0.652 
4 
0.122 
0.738 
5 
0.187 
0.813 
6 
0.262 
0.878 
7 
0.348 
0.933 
8 
0.444 
0.975 
9 
0.555 
0.997 
10 
0.692 
1.000 
 

 
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Sample Size Consideration for Immunogenicity 
Table 2 also applies to the sample size consideration for immunogenicity.  Within a group of 
size n=10, if there are two positive responders with respect to an immunogenicity endpoint, the 
95% confidence interval of the positive response rate has the lower bound of 0.025 and the upper 
bound of 0.556.  
 
Sample Size Consideration for Comparison 
For the comparison of positive response rate between three arms each of size n=10, we present in 
Table 3 the minimum event rate that can be detected with 80% or 90% power in the high-
responding arm over a range of possible event rates in the low-responding arm. If the positive 
response rate is 0.1 in the low-responding arm, this trial has 80% (or 90%) power to detect the 
between-arm difference if the positive response rate in the other arm is no less than 0.68 (or 
0.75). This calculation was performed based on Fisher’s exact test.  
For the comparison of the magnitude of immune response between two arms each of size n=10, 
the trial has 80% (or 90%) power to detect the between-arm difference if the effect size is no less 
than 1.20 (or 1.38); that is, the mean difference is no less than 1.20 (or 1.38) times the standard 
deviation of the immune response. This power calculation is based on two-sample t-test, and a 
log-transformation of the immune response may be needed if the data is close to being log-
normally distributed.  
Table 4: Minimum Event Rate That Can Be Detected With 80% Or 90% Power with 
Sample Size n=10 per Arm 
Rate in one 
arm 
Minimum rate in the other arm 
(80% power) 
Minimum rate in the other arm 
(90% power) 
0.1 
0.78 
0.84 
0.2 
0.88 
0.93 
0.3 
0.95 
0.985 
0.4 
0.995 
- 
Note: If the rate is 0.4, with a rate of 1 in the other arm the highest power that can be achieved is 
0.84.  
6.4 
Statistical Analysis 
All statistical analyses will be performed using Statistical Analysis System (SAS) (SAS Institute, 
Cary, NC), R, or S-Plus statistical software. No formal multiple comparison adjustments will be 
employed for safety endpoints or secondary endpoints. 
 
Analysis Variables 
The analysis variables consist of baseline variables and safety variables for primary and 
secondary objective analyses. 
 
Baseline Demographics 

 
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Baseline characteristics including demographics and laboratory measurements will be 
summarized using descriptive statistics. 
 
Safety Analysis  
6.4.3.1 
Solicited Reactogenicity  
The number and percentage of participants experiencing each type of reactogenicity sign or 
symptom will be tabulated by severity. For a given sign or symptom, each participant’s 
reactogenicity will be counted once under the maximum severity for all assessments. 
6.4.3.2 
Adverse Events 
AEs are coded into Medical Dictionary for Regulatory Activities (MedDRA) preferred terms. 
The number and percentages of participants experiencing each specific AE will be tabulated by 
severity and relationship to treatment. For the calculations in these tables, each participant’s AE 
will be counted once under the maximum severity or strongest recorded causal relationship to 
treatment. 
A complete listing of AEs for each participant will provide details including severity, 
relationship to treatment, onset, duration and outcome. 
6.4.3.3 
Local Laboratory Values 
Boxplots, violin plots, or beeswarm plots of local laboratory values will be generated for baseline 
values and for values measured during the course of the study. Each plot will show the 1st 
quartile, the median, and the 3rd quartile. Outliers, or values outside the boxplot, will also be 
plotted. If appropriate, horizontal lines representing boundaries for abnormal values will be 
plotted. 
 
Immunogenicity Analysis  
The statistical analysis for immunogenicity will employ the intent-to-treat principle whereby all 
data from enrolled subjects will be analyzed according to the group assignment. If needed, a per-
protocol analysis will be performed as secondary analysis where subjects will be analyzed 
according to their actual vaccination scheme if it is different from the assigned or up to the last 
visit in the study if there are early dropouts.  
If assay data are qualitative or dichotomous (i.e., positive or negative) then analyses will be 
performed by tabulating the frequency of positive response for each assay at each time point that 
an assessment is performed. Binomial response rates will be presented with their corresponding 
exact 95% confidence interval estimates. 
Some immunologic assays have underlying continuous or count-type readout that is often 
dichotomized into responder/non-responder categories. For these assays, graphical and tabular 
summaries of the underlying distributions will be made. These summaries may be performed on 
transformed data (e.g., log transformation) for ease of interpretation. 
 
Missing Data 
Missing responses will be assumed to be missing completely at random. Analyses will include 
all samples available at each study time point. Based on experience from previous trials, we 
expect missing data to be rare. Regardless, in the event of missing data, we will report the 

 
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occurrence and extent of missingness. We will also provide plausible explanations for the 
missingness mechanism, should such information be available. 
 
Interim Analyses 
Safety Reviews: The PSRT will review safety data routinely throughout the study. The study will 
utilize both electronic database features and reviews by designated safety review personnel to 
identify in a timely manner if any of the safety pause rules of the study are met.  
Immunogenicity Review: The mRNA-1215 dose of 10 mcg was chosen for Group 4 following an 
interim analysis of safety and immunogenicity data from enrollments in Groups 1-3 (Section 
4.6). Other interim analyses of immunogenicity may be performed prior to completion of safety 
follow-up visits or collection of data for secondary and exploratory immunogenicity endpoints.  

 
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7. 
PHARMACY AND VACCINE ADMINISTRATION 
PROCEDURES 
The study groups and study agent dosing schedule are shown in Table 1 in Section 4.1. 
7.1 
mRNA-1215 Vaccine, Pharmaceutical Formulation 
mRNA-1215 vaccine (also referred to as mRNA-1215 Injection) consists of mRNA encapsulated 
in a LNP and is administered by intramuscular (IM) injection. The mRNA Drug Substance is 
encapsulated by LNPs composed of four lipids: one of the lipids is the proprietary ionizable 
lipid, SM-102, and three are commercially available lipids, cholesterol, DSPC, and PEG2000 
DMG.  mRNA-1215 is sterile filtered and filled into glass vials at a total mRNA concentration of 
0.40 mg/mL and a volume of 0.8 mL. 
The vaccine manufacturer, ModernaTX, Inc, will deliver the vaccine vials to the DMID Clinical 
Materials Repository at Thermo Fisher Scientific, Germantown, MD, from where the vaccine 
will be distributed to the site.  
7.2 
Vaccine Storage 
mRNA-1215 is stored at -70°C (-90°C to -60°C). Stability protocols for mRNA-1215 will 
include at least 24-months duration at the intended storage temperature (-90°C to -60°C). 
The prepared doses are stable for clinical in-use for up to 8 hours at room temperature.  
 
Handling Information 
mRNA-1215 must be stored in a secure area with limited access (pharmacy staff only). The 
freezer should have an automated temperature recording and alert system. There must be an 
available back-up freezer. The freezers must be connected to a back-up generator, or alternate 
plan in the event of a power failure. The pharmacy must have in place a 24-hour alert system that 
allows for rapid response in case of freezer malfunctioning.  
Prepared doses should remain at ambient temperatures (20ºC to 25ºC) and should not be shaken 
or allowed to roll during transport. Avoid exposing to direct sunlight while the syringe is in route 
to the injection administration location. If the prepared doses require transportation to a separate 
facility, ensure there are appropriate transport procedures in place. Under all circumstances, the 
time for preparation, transportation and administration of mRNA-1215 must occur within 
maximum 9 (nine) hours from the time the vials are removed from the freezer, including about 1 
hour for a dose preparation and 8 hours stability of the prepared doses. 
A minimum of 20 minutes and a maximum of 30 minutes are allowed for equilibration of vial to 
controlled room temperature (20°C to 25°C) after removal from freezer. A maximum of 30 
minutes is allowed between completion of equilibration and completion of dosing syringes fill. 
However, all dosing syringes must be filled in quick succession once the vial is breached. 
 
Temperature Excursions 
If deviations in storage temperature occur from the normal allowance for the pharmacy freezer, 
the site pharmacist or designee must report the storage temperature excursion promptly to the PI 

 
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and IND Sponsor. The excursion must be evaluated and investigated, and action must be taken to 
restore and maintain the desired temperature limits. Pending the outcome of the investigation, the 
IND Sponsor will notify the pharmacist if continued clinical use of the product is acceptable. 
In the case of storage or shipping/handling temperature excursions outside of the normal 
allowance for the storage device, the following procedure is to be followed: 
1. Quarantine the affected product in a separate area. If the excursion results in thawed 
material for the investigational products, it must not be refrozen. Thawed vials must be 
quarantined at 5°C ± 3°C. Frozen vials must be quarantined at the labeled storage 
temperature of -70°C (-90°C to -60°C). 
2. Report the excursion to the IND sponsor’s authorized representative (SAR) or designee, 
any other parties required by site procedures, and via email to 
DMIDProductSupportTeam@niaid.nih.gov. Do not use the product until the IND 
Sponsor’s Authorized Representative (SAR) or designee informs the site pharmacist 
whether continued clinical use of the product is acceptable. 
3. After receipt and evaluation of the reported information, the Sponsor or manufacturer’s 
designee will notify the site pharmacist whether continued clinical use of the product is 
acceptable. 
4. The DMID process for temperature excursions is procedural and will be provided to the 
site.  
7.3 
Preparation of mRNA-1215 for Administration 
Pharmacists must follow the detailed instructions in the mRNA-1215 vaccine Preparation and 
Administration Worksheets. There are 4 worksheets in total, one for each dose level. The 
mRNA-1215 vaccine Dose Preparation and Administration Worksheets are in the Study Specific 
Procedures (SSP). 
Below are general guidelines for the product preparation. 
• 
One vial of vaccine is required to prepare each dose. 
• 
Pharmacists must follow appropriate aseptic technique and sterile preparation 
procedures/guidance as outlined in USP <797> [medium risk], utilizing a pharmacy 
biosafety cabinet/isolator or better. Local regulations and site institutional policies and 
procedures for use of personal protective equipment, such as gloves, gowns, masks, and 
safety glasses, must be followed. Pharmacists should follow the requirements of their 
country, their institution, and their pharmacy regulatory authority regarding these 
procedures.  
Any unused portion of study product will not be used for another participant. Empty vials, 
unused portion of entered vials, or unused prepared study product should be discarded in a 
biohazard container and disposed of in accordance with institutional or pharmacy policy. 
 
Dose Preparation 
The mRNA-1215 doses for administration in study groups will be prepared as described in Table 
5 below. 

 
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Table 5: mRNA-1215 Injection Dose Preparation Schema 
Detailed instructions for dose preparations are provided in the Pharmacy Manual. 
7.4 
Administration of mRNA-1215 Injection 
Clinician instructions on how to select an arm and administer an IM injection are in Section 
4.4.8.  Subjects will receive the vaccine by needle and syringe injection in either deltoid. 
Clinicians will choose the appropriate needle size for each subject. Product labeling verification 
and IM injection procedures will be performed consistent with institutional policies and standard 
procedures. 
7.5 
Study Product Accountability 
 
Documentation 
The study pharmacist or designee will be responsible for maintaining an accurate record of the 
codes, inventory, and an accountability record of the investigational study products supplies for 
this study. Electronic documentation as well as paper copies will be used. 
 
Disposition 
Empty vials and the unused portion of a vial will be discarded in a biohazard containment bag 
and incinerated or autoclaved in accordance with the institutional or pharmacy policy. Partially 
used vials will not be administered to other subjects or used for in vitro experimental studies. 
Any unopened vials that remain at the end of the study may be returned to DMID or discarded at 
the discretion of the sponsor in accordance with policies that apply to investigational agents. 
Vials will be disposed of in accordance with institutional or pharmacy policy. 
 
 
Dose 
Diluent (0.9% 
Sodium Chloride) 
volume (mL)
mRNA 1215 
volume 
(mL) 
Total volume 
in mixing vial 
(mL)
Injection Dose 
Volume (mL) 
Dosing Syringe 
Expiration 
(hours) 
25 mcg 
1.75 
0.25 
2 
0.5 
8 
50 mcg 
1.50 
0.50 
2 
0.5 
8 
100 mcg 
0.50 
0.50 
1 
0.5 
8 
10 mcg 
3.8 
0.2 
4 
0.5 
8 

 
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8. 
HUMAN SUBJECT PROTECTIONS AND ETHICAL 
OBLIGATIONS 
This research study will be conducted in compliance with the protocol, International Council for 
Harmonisation Good Clinical Practices (ICH-GCP) guidance, and all applicable regulatory 
requirements. 
8.1 
Institutional Review Board 
A copy of the protocol, ICF, other written subject-facing information, and any advertising 
material will be submitted to the IRB for written approval prior to use. 
The PI must submit and, where necessary, obtain approval from the IRB for all subsequent 
protocol amendments and changes to the ICF. The PI will notify the IRB of research events that 
occur on study as described in Section 5.8. 
The investigator will be responsible for obtaining IRB approval of the annual Continuing Review 
throughout the duration of the study. 
8.2 
Informed Consent 
The PI or designee is responsible for obtaining written informed consent from the subject after 
adequate explanation of the aims, methods, anticipated risks and benefits of the study and before 
any protocol-specific procedures or study product is administered. The AoU must be completed 
before the study ICF is signed. 
The study informed consent form (ICF) describes the investigational product to be used and all 
aspects involved in protocol participation. It is provided to potential participants for their review 
in advance, typically as a hard copy during screening as described in Section 4.4.4. Volunteers 
will have ample time to ask questions and discuss this study with NIH staff, and with their 
family, friends, and personal health care providers prior to signing the informed consent. 
Informed consent process is to be conducted in person, with only relevant parties present, to 
protect the privacy of the subject. The study clinicians that are listed as Associate Investigators 
on the study are authorized to obtain consent and to respond to volunteers’ questions as needed. 
Steps to reduce coercion or undue influence for volunteers who are NIH employees are described 
in the protocol Section 4.3.4.  
The acquisition of informed consent will be documented in the subject’s medical records, as 
required by 21 CFR 312.62, and the ICF will be signed and personally dated by the subject and 
the person who conducted the informed consent discussion. A copy of the signed ICF will be 
given to the subject and the original will be scanned into the electronic medical record. 
8.3 
Study Discontinuation and Closure  
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, the 
investigators, the Investigational New Drug (IND) and regulatory authorities as appropriate. If 

 
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the study is prematurely terminated or suspended, the PI will promptly inform study participants, 
the IRB, and Sponsor and will provide the reason(s) for the termination or suspension. Study 
participants will be contacted, as applicable, and be informed of changes to study visit schedule. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants 
• Demonstration of efficacy that would warrant stopping    
• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
• Determination that the primary endpoint has been met 
• Determination of futility 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the Sponsor, IRB, Office for Human Research Protections (OHRP), and/or 
FDA. 
8.4 
Confidentiality and Privacy 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the Sponsor(s) and their representatives. This confidentiality is extended to cover 
testing of biological samples and genetic tests in addition to the clinical information relating to 
participants. Therefore, the study protocol, documentation, data, and all other information 
generated will be held in strict confidence. No information concerning the study, or the data will 
be released to any unauthorized third party without prior written approval of the IND sponsor.  
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the Sponsor (DMID), representatives of 
the VRC, representatives of the IRB, and/or regulatory agencies may inspect all documents and 
records required to be maintained by the investigator, including but not limited to, medical 
records (office, clinic, or hospital) and pharmacy records for the participants in this study.  The 
clinical study site will permit access to such records. 
The study participant’s contact information will be securely stored at the clinical site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure 
location for as long a period as dictated by the reviewing IRB, Institutional policies, or Sponsor 
requirements. 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted to and stored by The Emmes Company, LLC (Rockville, MD), the 
Data Coordinating Center. This will not include the participant’s contact or identifying 
information. Rather, individual participants and their research data will be identified by a unique 
study identification number. The study data entry and study management systems used by the 
clinical site and by Emmes research staff will be secured and password protected. At the end of 
the study, all study databases will be de-identified and archived. 

 
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To further protect the privacy of study participants, a Certificate of Confidentiality has been 
issued by the National Institutes of Health (NIH).  This certificate protects identifiable research 
information from forced disclosure. It allows the investigator and others who have access to 
research records to refuse to disclose identifying information on research participation in any 
civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or 
local level. By protecting researchers and institutions from being compelled to disclose 
information that would identify research participants, Certificates of Confidentiality help achieve 
the research objectives and promote participation in studies by helping assure confidentiality and 
privacy to participants. 
8.5 
Risks and Benefits Assessment  
 
Risks of mRNA-1215  
This is the first study in humans of the investigational vaccine, mRNA-1215, and therefore risks 
are unknown at the time of study start. The risks listed below are those associated with the 
administration of vaccines in general, including other mRNA-based vaccines.  
Subjects may exhibit general signs and symptoms associated with vaccine administration, 
including fever, chills, rash, nausea/vomiting, headache, dizziness, joint pain, and fatigue. 
Potential side effects of IM vaccine injection include pain/tenderness, stinging, pruritis, arm 
discomfort, redness of the skin or mild bruising at vaccine injection site. Axillary 
lymphadenopathy on the same side as vaccination has also occurred with other mRNA vaccines. 
These side effects will be monitored, but are generally short term, mild to moderate severity and 
usually do not require treatment.  
There is a very small chance of allergic reactions, including anaphylaxis, as has been observed 
with mRNA platforms and other vaccines. There is also a rare possibility of developing chronic 
urticaria. 
There have been very rare reports of myocarditis and pericarditis occurring after vaccination 
with COVID-19 mRNA vaccines. The majority of the cases have been reported in males and 
females shortly after the second dose of the vaccine. The risk is highest in males under the age of 
40 years, specifically males between 12 through 17 years of age.  Symptoms of myocarditis or 
pericarditis include chest pain, shortness of breath, or feelings of having a fast-beating, fluttering, 
or pounding heart, with onset of symptoms most commonly reported within a few days following 
vaccination.  Study participants should seek medical attention and also notify study site staff if 
any of these symptoms occur following vaccination. While some cases required intensive care 
support, available data from short-term follow up suggest that most cases had resolution of 
symptoms with conservative management. Information is not yet available about potential long-
term sequelae. It is not known whether the risk of myocarditis or pericarditis is increased 
following additional doses of the vaccine. Investigators and study participants should be alert to 
the signs and symptoms of myocarditis and pericarditis [48].  
There may be other unknown side effects. 
 
Risks of Specimen Collection  

 
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• Blood drawing: The risks of blood sample collection are minimal and consist of mild 
discomfort at the sample collection site. The procedure may cause pain, bruising, 
lightheadedness or fainting, and, rarely, infection at the site where the blood is taken. 
• Apheresis: The procedure may cause pain, bruising, and discomfort in the arms where the 
needles are placed. It may also cause chills, nausea, heartburn, mild muscle cramps and 
tingling sensation around the mouth or in the fingers, however this can usually be relieved 
by slowing or temporarily interrupting the apheresis procedure or taking a calcium 
containing antacid, such as Tums®. Other possible side effects are anxiety, vomiting and 
lightheadedness. Temporary lowering of the blood pressure may develop. There is the rare 
possibility of infection, fainting or seizure. Very rarely a nerve problem at the needle 
placement site may occur. Also, very rarely, a machine malfunction may occur, resulting in 
the loss of about one unit of blood. There may be additional risks of apheresis that are 
unknown at this time. 
 
Risks of mRNA-1215 for the Fetus or Nursing Infant 
We do not know the possible effects of the study vaccine on the fetus or nursing infant. Women 
of reproductive potential will be required to agree to use an effective method of birth control 
beginning 21 days prior to enrollment and continuing through end of study. 
Because this is a research study, women of reproductive potential will be tested for pregnancy 
prior to administration of study injection and asked to notify the site immediately upon learning 
of a pregnancy during this study. In the case of pregnancy, subjects will continue to be followed 
for safety. Research sample collections, study procedures and additional product administrations 
will be discontinued for pregnant women. The subject will be contacted to ask about the outcome 
of a pregnancy that begins during the study. 
 
Risks of New Diagnoses 
It is possible that the standard medical tests performed as part of this research protocol will result 
in new diagnoses. Depending upon the medical findings and consequences of being provided 
with the new medical information about health status, the study subject may view this aspect of 
study participation as either a risk or a benefit. Any such information will be shared and 
discussed with the subject and, if requested by the subject, will be forwarded to the subject’s 
primary health care provider for further workup and management. 
 
Potential Benefits 
Study subjects will not receive direct health benefit from study participation. This protocol is not 
designed to provide treatment for any condition. Others may benefit from knowledge gained in 
this study that may aid in the development of a Nipah Virus vaccine. The investigational vaccine 
is not expected to provide protection from Nipah Virus infection.  
 
Assessment of Potential Risks and Benefits 
This healthy volunteer trial to evaluate the safety and immunogenicity of mRNA-1215 was 
reviewed using the VRC Risk Management Plan. Potential risks, acceptance of risks, and 
mitigation strategies are available in the VRC 322/DMID 21-0016 Risk Register. 

 
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8.6 
Plan for Use and Storage of Biological Samples 
The plan for use and storage of biological samples from this protocol is as outlined in the 
following sections. 
 
Use of Samples, Specimens and Data 
Samples, specimens and data collected under this protocol may be used to conduct protocol-
related safety, and immunogenicity evaluations, exploratory laboratory evaluations related to 
NiV, exploratory laboratory evaluations related to mAb, vaccine or infectious disease research in 
general and for research assay validation.   
Stored samples may also be used later for evaluation of exploratory genetic factors that may 
influence the immune response to vaccination. For example, this could include RNA 
transcriptome, immunoglobulin genes, and polymorphisms, in pattern recognition receptors 
(PRRs), such as Toll-like receptor (TLR) or RIG-like receptor (RLR) genes. In addition, it could 
include many single-nucleotide polymorphisms (SNPs) in other genes, for example, those coding 
for cytokines, viral, or vitamin receptors that are experimentally associated with variations in 
vaccine responses. Other optional analysis, including proteome, lipidome, metabolome, and 
exosome may be done on collected specimens to evaluate some proteins, lipids, metabolites, and 
low molecular weight molecules involved in the immune response to vaccination.  
No specific results will be provided to participants or their health care providers because we will 
not be investigating genetic analyses that have known medical diagnoses (e.g. Huntington’s 
disease) or other medically actionable genetic information. 
No personal identifiable information will be shared since the results will only be shared with a 
code.  
 
Storage and Tracking of Blood Samples and Other Specimens 
All of the stored study research samples are labeled by a code that only the site can link to the 
subject. Samples are stored at the VIP, Gaithersburg, MD or VRC laboratories in Building 40, 
Bethesda, MD, which are both secure facilities with limited access. Data will be kept in 
password-protected computers. Only investigators or their designees will have access to the 
samples and data. Samples will be tracked in the Laboratory Information Management System 
(LIMS) database or using another software designed for this purpose (e.g., Freezerworks). 
 
Disposition of Samples, Specimens and Data at Completion of the 
Protocol 
In the future, other investigators (both at NIH and outside) may wish to study these samples 
and/or data. IRB approval must be sought prior to any sharing of samples. Any clinical 
information shared about those samples would similarly require prior IRB approval. The 
research use of stored, unlinked or unidentified samples may be exempt from the need for 
prospective IRB review and approval.  
At the time of protocol termination, samples will remain in the VIP facility or VRC laboratories 
or, after IRB approval, transferred to another repository. Regulatory oversight of the stored 
samples and data may be transferred to a stored samples protocol as part of the IRB-approved 
termination plan. Data will be archived by the VRC/DMID in compliance with requirements for 

 
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retention of research records, or after IRB and study sponsor approval, it may be either destroyed 
or transferred to another repository. 
 
Loss or Destruction of Samples, Specimens or Data 
Any loss or unanticipated destruction of samples (for example, due to freezer malfunction) or 
data (for example, misplacing a printout of data with identifiers) that compromises the scientific 
integrity of the study will be reported to the IRB in accordance with institutional policies. The PI 
will also notify the IRB if the decision is made to destroy the remaining samples. 
8.7 
Safety Oversight 
 
Protocol Safety Review Team  
Close cooperation between the designated members of the Protocol Team will occur to evaluate 
and respond to individual AEs in a timely manner. The VRC designated Safety Officer conducts 
a daily safety review of clinical data per VRC Standard Operating Procedures.  
The PSRT is comprised of the PI, Associate Investigators, Study Coordinator, Protocol 
Specialists, and other study clinicians. In addition, PSRT may include IND Sponsor 
representatives, the DMID Medical Monitor (MM), representative(s) from the product 
manufacturer, and an independent medical expert as needed.  
PSRT will review the summary study safety data reports on a weekly basis through 4 weeks after 
the last subject receives the final study injection. After this time, the PSRT will monitor the 
safety data reports on a monthly basis through completion of the last study visit. 
 
Safety Monitoring Committee (SMC) 
The SMC is an independent group of at least 3 experts that monitors subject safety and advises 
DMID. SMC members will be separate and independent of study personnel participating in this 
trial and should not have scientific, financial, or other conflicts of interest related to this trial. 
The SMC will consist of members with appropriate expertise to contribute to the interpretation of 
data from this trial. A quorum will consist of a simple majority. 
The SMC will hold an organizational meeting prior to enrollment. At this meeting, the SMC will 
review the charter, protocol, ICF, and safety report template. 
For periodic e-review and evaluation of the accumulated study data for participant safety, study conduct, 
and progress, the SMC will receive the following: 
• Tabulated AEs and study characteristics (demographics, enrollment, etc) based on data 
through day 15 after each cohort is enrolled; 
• All SAEs, AESI and MAAEs. 
After the organizational meeting, no routine meetings of the SMC are needed.  The SMC will 
conduct ad hoc meetings for the following: 
• As requested by the SMC (based on AE or SAEs); 
• When trial-level halting criteria are met; 
• At the request of DMID to review a potential safety concern identified by either the PI, 
DMID Medical Monitor, or Protocol Safety Review Team (PSRT). 

 
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Procedures for SMC reviews/meetings are defined in the SMC charter. If ad hoc meetings are 
needed, the SMC will review applicable data including, but not limited to, enrollment, 
demographics, dosing, data, laboratory data and safety data at scheduled time points during this 
trial as defined in the SMC charter. Additional data may be requested by the SMC. As an 
outcome of each review/meeting, the SMC will make a recommendation as to the advisability of 
proceeding with study drug administration, and to continue, modify, or terminate this trial. 
Once approved by the Chair, the SMC recommendations will be forwarded to the DMID Clinical 
Project Manager and MM for their review and approval and inclusion of action items for 
implementation, as applicable. The SMC final signed recommendations will be distributed to the 
SMC Members, the investigator(s), and the Study Team within three (3) business days. 
 
 
 

 
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9. 
ADMINISTRATIVE AND OPERATIONAL 
OBLIGATIONS 
9.1 
Protocol Amendments  
Protocol amendments must be made only with prior approval of the IND Sponsor and with 
agreement from the PI and MO. All study amendments will be submitted to the IRB for 
approval. 
The IND Sponsor, the IRB, OHRP, the PI, Protocol Chairs, and/or the FDA reserve the right to 
terminate the study. The PI will notify the IRB in writing of the study’s completion or early 
termination. 
9.2 
Study Documentation and Storage 
The PI will delegate the study responsibilities to the study team, and a list of appropriately 
qualified persons to whom trial duties have been delegated will be maintained. 
Source documents are original data, records, and other information associated with and 
concerning the subject. These include but are not limited to hospital records, clinical and office 
charts, laboratory and pharmacy records, and correspondence. Long-term storage of source 
documents may be in the form of electronic files. 
The PI and staff are responsible for maintaining a comprehensive and centralized filing system of 
all study-related (essential) documentation, suitable for inspection at any time by representatives 
of the IND Sponsor (DMID), the VRC/NIAID/NIH, IRB, NIH, FDA, and/or applicable 
regulatory authorities. Elements include: 
 Subject files containing completed informed consent forms and supporting copies of 
source documentation. 
 Study files containing the protocol with all amendments, IBs, copies of all 
correspondence with the IRB. 
In addition, all original source documentation must be maintained and be readily available.  
All essential documentation should be retained by the institution for the same period of time 
required for medical records retention. The FDA requires study records to be retained for up to 
three years after marketing approval or refusal (21 CFR 312.62). If no marketing application is 
filed, or if the application is not approved, the records will be retained for two years after the 
investigation is discontinued and the FDA is notified. The HHS protection of human subjects’ 
regulations require that institutions retain records of IRB/EC activities and documentation of 
informed consent of subjects for at least 3 years after study completion (45 CFR 46). 
No study document should be destroyed without prior written agreement between the VRC, 
DMID and the investigator. Should the investigator wish to assign the study records to another 
party or move them to another location, they must notify the VRC in writing of the new 
responsible person and/or the new location. 
9.3 
Clinical Monitoring  

 
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Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants 
are protected, that the reported trial data are accurate, complete, and verifiable, and that the 
conduct of the trial is in compliance with the currently approved protocol/amendment(s), with 
ICH GCP, and with applicable regulatory requirement(s).  
Monitoring for this study will be performed as designated by the IND Sponsor, DMID. DMID 
may collaborate with the VRC Clinical Monitoring Oversight Group as needed.  
9.4 
Data Collection and Data Sharing  
 
Data Collection 
Clinical research data will be collected in a secure electronic web-based clinical data 
management system (CDMS) through a CRO, The Emmes Company, LLC (Rockville, MD). 
Extracted data without patient identifiers will be sent to the Protocol Statistician for statistical 
analysis. 
 
Source Documents 
The site will maintain appropriate medical and research records for this trial, in compliance with 
ICH E6(R2) GCP, applicable regulations, and institutional requirements for the protection of 
confidentiality of subjects. Source data are all information, original records of clinical findings, 
observations, or other activities in a clinical trial necessary for the reconstruction and evaluation 
of the trial. Examples of these original documents and data records include, but are not limited 
to, medical records, laboratory reports, pharmacy records and other research records maintained 
for the clinical trial. 
 
Data Sharing Plan 
Data generated in this study will be shared as de-identified data in the government-funded public 
repository, www.ClinicalTrials.gov. Data may be shared prior to publication at approved public 
presentations or for collaborative development and will be shared at the time of publication or 
within 1 year of the primary completion date.  
9.5 
Quality Assurance and Quality Control  
The clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion. The VEC’s Quality Management Plan will 
be used to perform quality management for this trial. 
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site for clarification/resolution. 
The monitors will verify that the clinical trial is conducted, and data are generated, and 
biological specimens are collected, documented (recorded), and reported in compliance with the 
protocol, ICH GCP, and applicable regulatory requirements. 
9.6 
Language 

 
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All written information and other material to be used by subjects and investigative staff must use 
vocabulary and language that are clearly understood by the subject. 
9.7 
Research-Related Injuries  
The NIH CC will provide short-term medical care for any injury resulting from participation in 
this research. In general, the NIH, the NIH CC, or the U.S. Federal Government will provide no 
long-term medical care or financial compensation for research-related injuries. 
 

 
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10. 
REFERENCES 
 
1. 
Marsh, G.A., et al., Cedar virus: a novel Henipavirus isolated from Australian bats. 
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2. 
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Infect Dis, 2005. 11(10): p. 1594-7. 
3. 
Goh, K.J., et al., Clinical features of Nipah virus encephalitis among pig farmers in 
Malaysia. N Engl J Med, 2000. 342(17): p. 1229-35. 
4. 
Chadha, M.S., et al., Nipah virus-associated encephalitis outbreak, Siliguri, India. Emerg 
Infect Dis, 2006. 12(2): p. 235-40. 
5. 
Arankalle, V.A., et al., Genomic characterization of Nipah virus, West Bengal, India. 
Emerg Infect Dis, 2011. 17(5): p. 907-9. 
6. 
Arunkumar, G., et al., Outbreak Investigation of Nipah Virus Disease in Kerala, India, 
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7. 
Gurley, E.S., et al., Person-to-person transmission of Nipah virus in a Bangladeshi 
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8. 
Luby, S.P., et al., Recurrent zoonotic transmission of Nipah virus into humans, 
Bangladesh, 2001-2007. Emerg Infect Dis, 2009. 15(8): p. 1229-35. 
9. 
Sweileh, W.M., Global research trends of World Health Organization's top eight 
emerging pathogens. Global Health, 2017. 13(1): p. 9. 
10. 
Clayton, B.A., et al., The Nature of Exposure Drives Transmission of Nipah Viruses from 
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11. 
Mire, C.E., et al., Pathogenic Differences between Nipah Virus Bangladesh and Malaysia 
Strains in Primates: Implications for Antibody Therapy. Sci Rep, 2016. 6: p. 30916. 
12. 
Clayton, B.A., et al., Transmission routes for nipah virus from Malaysia and Bangladesh. 
Emerg Infect Dis, 2012. 18(12): p. 1983-93. 
13. 
Sazzad, H.M., et al., Nipah virus infection outbreak with nosocomial and corpse-to-
human transmission, Bangladesh. Emerg Infect Dis, 2013. 19(2): p. 210-7. 
14. 
Chua, K.B., et al., Fatal encephalitis due to Nipah virus among pig-farmers in Malaysia. 
Lancet, 1999. 354(9186): p. 1257-9. 
15. 
Hsu, V.P., et al., Nipah virus encephalitis reemergence, Bangladesh. Emerg Infect Dis, 
2004. 10(12): p. 2082-7. 
16. 
Abdullah, S. and C.T. Tan, Henipavirus encephalitis. Handb Clin Neurol, 2014. 123: p. 
663-70. 
17. 
Lo, M.K. and P.A. Rota, The emergence of Nipah virus, a highly pathogenic 
paramyxovirus. J Clin Virol, 2008. 43(4): p. 396-400. 
18. 
Prescott, J., et al., The immune response to Nipah virus infection. Arch Virol, 2012. 
157(9): p. 1635-41. 
19. 
Wong, K.T. and C.T. Tan, Clinical and pathological manifestations of human 
henipavirus infection. Curr Top Microbiol Immunol, 2012. 359: p. 95-104. 
20. 
Ching, P.K., et al., Outbreak of henipavirus infection, Philippines, 2014. Emerg Infect 
Dis, 2015. 21(2): p. 328-31. 
21. 
AbuBakar, S., et al., Isolation and molecular identification of Nipah virus from pigs. 
Emerg Infect Dis, 2004. 10(12): p. 2228-30. 

 
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22. 
Ang, B.S.P., T.C.C. Lim, and L. Wang, Nipah Virus Infection. J Clin Microbiol, 2018. 
56(6). 
23. 
Chua, K.B., Risk factors, prevention and communication strategy during Nipah virus 
outbreak in Malaysia. Malays J Pathol, 2010. 32(2): p. 75-80. 
24. 
Field, H., et al., The natural history of Hendra and Nipah viruses. Microbes Infect, 2001. 
3(4): p. 307-14. 
25. 
Geisbert, T.W., H. Feldmann, and C.C. Broder, Animal challenge models of henipavirus 
infection and pathogenesis. Curr Top Microbiol Immunol, 2012. 359: p. 153-77. 
26. 
Glennon, E.E., et al., Domesticated animals as hosts of henipaviruses and filoviruses: A 
systematic review. Vet J, 2018. 233: p. 25-34. 
27. 
Yob, J.M., et al., Nipah virus infection in bats (order Chiroptera) in peninsular Malaysia. 
Emerg Infect Dis, 2001. 7(3): p. 439-41. 
28. 
Donaldson, H. and D. Lucey, Enhancing preparation for large Nipah outbreaks beyond 
Bangladesh: Preventing a tragedy like Ebola in West Africa. Int J Infect Dis, 2018. 72: p. 
69-72. 
29. 
Halpin, K., et al., Pteropid bats are confirmed as the reservoir hosts of henipaviruses: a 
comprehensive experimental study of virus transmission. Am J Trop Med Hyg, 2011. 
85(5): p. 946-51. 
30. 
Rahman, S.A., et al., Characterization of Nipah virus from naturally infected Pteropus 
vampyrus bats, Malaysia. Emerg Infect Dis, 2010. 16(12): p. 1990-3. 
31. 
Yadav, P.D., et al., Detection of Nipah virus RNA in fruit bat (Pteropus giganteus) from 
India. Am J Trop Med Hyg, 2012. 87(3): p. 576-8. 
32. 
Bloom, D.E. and D. Cadarette, Infectious Disease Threats in the Twenty-First Century: 
Strengthening the Global Response. Front Immunol, 2019. 10: p. 549. 
33. 
Loomis, R.J., et al., Structure-Based Design of Nipah Virus Vaccines: A Generalizable 
Approach to Paramyxovirus Immunogen Development. Front Immunol, 2020. 11: p. 842. 
34. 
Loomis, R.J., et al., Chimeric Fusion (F) and Attachment (G) Glycoprotein Antigen 
Delivery by mRNA as a Candidate Nipah Vaccine. Front Immunol, 2021. 12: p. 772864. 
35. 
Baden, L.R., et al., Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl 
J Med, 2021. 384(5): p. 403-416. 
36. 
Polack, F.P., et al., Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N 
Engl J Med, 2020. 383(27): p. 2603-2615. 
37. 
Anderson, E.J., et al., Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in 
Older Adults. N Engl J Med, 2020. 383(25): p. 2427-2438. 
38. 
Jackson, L.A., et al., An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N 
Engl J Med, 2020. 383(20): p. 1920-1931. 
39. 
Corbett, K.S., et al., SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen 
preparedness. Nature, 2020. 586(7830): p. 567-571. 
40. 
Corbett, K.S., et al., Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in 
Nonhuman Primates. N Engl J Med, 2020. 383(16): p. 1544-1555. 
41. 
Corbett, K.S., et al., Immune Correlates of Protection by mRNA-1273 Immunization 
against SARS-CoV-2 Infection in Nonhuman Primates. bioRxiv, 2021. 
42. 
Vogel, A.B., et al., BNT162b vaccines protect rhesus macaques from SARS-CoV-2. 
Nature, 2021. 592(7853): p. 283-289. 

 
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43. 
Laczko, D., et al., A Single Immunization with Nucleoside-Modified mRNA Vaccines 
Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice. 
Immunity, 2020. 53(4): p. 724-732 e7. 
44. 
Lederer, K., et al., SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific 
Germinal Center Responses Associated with Neutralizing Antibody Generation. 
Immunity, 2020. 53(6): p. 1281-1295 e5. 
45. 
Wrapp, D., et al., Cryo-EM structure of the 2019-nCoV spike in the prefusion 
conformation. Science, 2020. 367(6483): p. 1260-1263. 
46. 
Ruggeberg, J.U., et al., Anaphylaxis: case definition and guidelines for data collection, 
analysis, and presentation of immunization safety data. Vaccine, 2007. 25(31): p. 5675-
84. 
47. 
Aretz, H.T., et al., Myocarditis. A histopathologic definition and classification. Am J 
Cardiovasc Pathol, 1987. 1(1): p. 3-14. 
48. 
Gargano, J.W., et al., Use of mRNA COVID-19 Vaccine After Reports of Myocarditis 
Among Vaccine Recipients: Update from the Advisory Committee on Immunization 
Practices - United States, June 2021. MMWR Morb Mortal Wkly Rep, 2021. 70(27): p. 
977-982. 
49. 
Ferreira, V.M., et al., Cardiovascular Magnetic Resonance in Nonischemic Myocardial 
Inflammation: Expert Recommendations. Journal of the American College of Cardiology, 
2018. 72(24): p. 3158-3176. 
50. 
Adler, Y., et al., 2015 ESC Guidelines for the diagnosis and management of pericardial 
diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of 
the European Society of Cardiology (ESC)Endorsed by: The European Association for 
Cardio-Thoracic Surgery (EACTS). European Heart Journal, 2015. 36(42): p. 2921-2964. 
 
 

 
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APPENDIX I: SCHEDULE OF EVALUATIONS 

 
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VRC 500 
VRC 322/DMID 20-0016: Group 1, Group 2, Group 3 and Group 4 (25, 50, 100 and 10 mcg of mRNA-1215 IM, respectively) 
Visit Number 
*01 
02 
02A 
03 
04 
05 
05A 
06 
07 
08 
09 
12 
14 
16 
18 
20 
Week of Study 
-8 to 0 
W0 
W1 
W1 
W2 
W4 
W4 
W5 
W6 
W8 
W12 
W16 
W24 
W32 
W44 
W56 
Day of Study 
-56 to 0 
1D0 
D1 
D7 
D14 
D28 
D29 
D35 
D42 
D56 
D84 
D112 
D168 
D224 
D308 
D392 
Clinical 
Tube^ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*VRC 500 Screening Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VRC 322/DMID 21-0016 AoU; 
Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2Physical exam  
X 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
3Medical history  
X 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
4Study Product Administration 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Phone evaluation (clinic visit as 
needed) 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Begin diary card 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
5Pregnancy test: urine or serum 
 
X 
X 
 
 
 
X 
 
 
6[X] 
 
 
 
 
 
X 
 
5Pregnancy Prevention 
Counseling/Reproductive Form 
 
X 
X 
 
 
 
X 
 
 
6[X] 
 
 
 
 
 
X 
 
CBC with differential 
EDTA 
3 
3 
 
3 
 
3 
 
3 
 
3 
 
 
 
 
3 
 
Total bilirubin, AST, ALT, ALP  
GLT 
4 
4 
 
4 
 
4 
 
4 
 
4 
 
 
 
 
4 
 
Creatinine 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
X 
 
HIV (other tests, if needed) 
EDTA 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Research Samples 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum  
SST 
16 
16 
- 
8 
8 
16 
- 
8 
16 
8 
8 
8 
8 
8 
8 
8 
PBMC and plasma  
EDTA 
20 
40 
- 
20 
20 
40 
- 
80 
7120 or 
apheresis 
20 
40 
40 
40 
40 
40 
40 
Daily Volume (mL) 
 
46 
63 
0 
35 
28 
63 
0 
95 
136 
35 
48 
48 
48 
48 
55 
48 
Max. Cumulative Volume (mL) 
 
46 
109 
109 
144 
172 
235 
235 
330 
466 
501 
549 
597 
645 
693 
748 
796 
Visit windows: Schedule Visits 02A – 5 with respect to Visit 02 and Visits 05A – 20 with respect to Visit 05 per the following visit windows:  
Visits 02A, 05A (+1 day). Visit 03 and 06 (±1 day). Visits 04, 05, 07 (± 2 days). Visits 08, 09, 12, 14, 16, 18, 20 (±7 days).  
 
Footnotes continue to next page

 
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* VRC 500: Screening evaluations must be no more than 56 days prior to Day 0 to be used for eligibility (negative pregnancy test 
from Day 0 must be used for eligibility). If clinical assessment on Day 0 suggests significant changes may have occurred since 
screening, then physical examination & clinical laboratory studies done on Day 0 are used for eligibility. Research blood samples may 
be collected at any time during screening through enrollment and are not to be restricted to the 56-day prior to enrollment.  
^ Tube: Tube types and volumes are shown to meet current institutional requirements and projected blood volumes. Different tubes for clinical 
evaluations may be used to meet site requirements. Slightly different volumes of tubes may be used for research blood samples when tube sizes as 
shown are not available, or as otherwise instructed by the IND Sponsor. Samples for safety and primary immunogenicity evaluations should be 
collected first, and other research samples as permitted with adequate supplies. Collected blood volumes will stay within the NIH CC blood draw 
limits for each subject. 
1 Day 0=day of enrollment and vaccine injection. Day 0 evaluations prior to injection are the baseline for assessing adverse events subsequently. 
2 Screening visit includes physical exam with vital signs. Weight should be measured at screening and on Visit 02. At other visits, physical exam is 
done if indicated. Otherwise, only blood pressure (BP), pulse, temperature, and respiration are required. 
3 Perform medical history targeted to eligibility at screening, then interim medical history 
4 Study Product Administration: Complete post vaccination evaluations (BP, pulse, temperature, respiration and injection site assessment) at 30 
minutes or longer after injection. 
5 Negative pregnancy test results must be confirmed for women of reproductive potential prior to study injection. 
6 For women of reproductive potential, pregnancy test must be negative within 72 hours prior to apheresis procedure. Brackets [ ] indicate optional 
as needed for those who complete apheresis. 
7 If optional apheresis occurs, ONLY draw 16 mL in SST (DO NOT draw 120 ml in EDTA tubes)  

 
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VRC 500 
VRC 322/DMID 20-0016: Subjects with discontinued vaccination schedule** 
Visit Number 
*01 
02 
02A 
03 
04 
05 
08 
09 
13 
15 
17 
19 
Week of Study 
-8 to 0 
W0 
W1 
W1 
W2 
W4 
W8 
W12 
W20 
W28 
W40 
W52 
Day of Study 
-56 to 0 
1D0 
D1 
D7 
D14 
D28 
D56 
D84 
D140 
D196 
D280 
D364 
Clinical 
Tube 
 
 
 
 
 
 
 
 
 
 
 
 
*VRC 500 Screening Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
VRC 322/DMID 21-0016 AoU; 
Consent 
 
X 
 
 
 
 
 
 
 
 
 
 
2Physical exam  
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
3Medical history  
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
4Study Product Administration 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Phone evaluation (clinic visit as 
needed) 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Begin diary card 
 
 
X 
 
 
 
 
 
 
 
 
 
 
5Pregnancy test: urine or serum 
 
X 
X 
 
 
6[X] 
 
 
 
 
 
X 
 
5Pregnancy Prevention 
Counseling/Reproductive Form 
 
X 
X 
 
 
6[X] 
 
 
 
 
 
X 
 
CBC with differential 
EDTA 
3 
3 
 
3 
 
3 
 
 
 
 
3 
 
Total bilirubin, AST, ALT, ALP  
GLT 
4 
4 
 
4 
 
4 
 
 
 
 
4 
 
Creatinine 
 
X 
X 
 
X 
 
X 
 
 
 
 
X 
 
HIV (other tests, if needed) 
EDTA 
3 
 
 
 
 
 
 
 
 
 
 
 
Research Samples 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum  
SST 
16 
16 
- 
16 
16 
8 
8 
8 
8 
8 
8 
8 
PBMC and plasma  
EDTA 
20 
40 
- 
80 
7120 or 
apheresis 
40 
40 
40 
40 
40 
40 
40 
Daily Volume (mL) 
 
46 
63 
0 
103 
136 
55 
48 
48 
48 
48 
55 
48 
Max. Cumulative Volume (mL) 
 
46 
109 
109 
212 
348 
403 
451 
499 
547 
595 
650 
698 
**This is a suggested schedule for subjects with discontinued product administration that can be followed by PI or designee discretion 
Footnotes continue to next page 
 

 
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Visit windows: Schedule Visits 02A – 19 with respect to Visit 02 per the following visit windows:  
Visits 02A (+1 day). Visit 03 (±1 day). Visits 04, 05 (±2 days). Visits 08, 09, 13, 15, 17, 19 (±7 days).  
* VRC 500: Screening evaluations must be no more than 56 days prior to Day 0 to be used for eligibility (negative pregnancy test from Day 0 
must be used for eligibility). If clinical assessment on Day 0 suggests significant changes may have occurred since screening, then physical 
examination & clinical laboratory studies done on Day 0 are used for eligibility. Research blood samples may be collected at any time during 
screening through enrollment and are not to be restricted to the 56-day prior to enrollment. 
^ Tube: Tube types and volumes are shown to meet current institutional requirements and projected blood volumes. Different tubes for clinical 
evaluations may be used to meet site requirements. Slightly different volumes of tubes may be used for research blood samples when tube sizes as 
shown are not available, or as otherwise instructed by the IND Sponsor. Samples for safety and primary immunogenicity evaluations should be 
collected first, and other research samples as permitted with adequate supplies. Collected blood volumes will stay within the NIH CC blood draw 
limits for each subject. 
1 Day 0=day of enrollment and vaccine injection. Day 0 evaluations prior to injection are the baseline for assessing adverse events subsequently. 
2 Screening visit includes physical exam with vital signs. Weight should be measured at screening and on Visit 02. At other visits, physical exam is 
done if indicated. Otherwise, only blood pressure (BP), pulse, temperature, and respiration are required. 
3 Perform medical history targeted to eligibility at screening, then interim medical history  
4 Study Product Administration: Complete post vaccination evaluations (BP, pulse, temperature, respiration and injection site assessment) at 30 
minutes or longer after injection. 
5 Negative pregnancy test results must be confirmed for women of reproductive potential prior to study injection. 
6 For women of reproductive potential, pregnancy test must be negative within 72 hours prior to apheresis procedure. Brackets [ ] indicate optional 
as needed for those who complete apheresis. 
7 If optional apheresis occurs, ONLY draw 16 mL in SST (DO NOT draw 120 ml in EDTA tubes)   

 
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APPENDIX II: ASSESSMENT OF RELATIONSHIP TO VACCINE AND GRADING 
SEVERITY OF ADVERSE EVENTS

 
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Assessment of Relationship of an Adverse Event to Study Vaccine:  
The relationship between an AE and the vaccine will be assessed by the investigator on the basis 
of his or her clinical judgment and the definitions below. 
• Definitely Related. The AE and administration of study agent are related in time, and a 
direct association can be demonstrated. 
• Probably Related. The AE and administration of study agent are reasonably related in 
time, and the AE is more likely explained by study agent than other causes.  
• Possibly Related. The AE and administration of study agent are reasonably related in 
time, but the AE can be explained equally well by causes other than study agent. 
• Not Related. The AE is clearly explained by another cause not related to the study 
product.  
For purposes of preparing summary data reports in which AE attributions are simplified to 
“Related” or “Not Related”, in this protocol, the “Definitely, Probably and Possibly” attributions 
above will be mapped to the “Related” category while the “Unlikely/Probably Not Related” and 
“Not Related” attributions above will be mapped to the “Not Related” category. The definitions 
that apply when these two attribution categories alone are used are as follows: 
• Related – There is a reasonable possibility that the AE may be related to the study 
product(s). 
• Not Related – There is not a reasonable possibility that the AE is related to the study 
product(s). 
Grading the Severity of Adverse Events: 
The FDA Guidance for Industry (September 2007): “Toxicity Grading Scale for Healthy Adult 
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” is the basis for the 
severity grading of AEs in this protocol. Several modifications were made to the table as follows: 
• “Emergency room visit” is not automatically considered a life-threatening event; these 
words have been removed from any “Grade 4” definition where they appear in the table 
copied from the guidance document. 
• Laboratory value shown as a “graded” value in the table that is within the institutional 
normal range will not be severity graded or recorded as an AE. 
• Severity grading for hemoglobin decrease on the basis of the magnitude of decrease from 
baseline is not applicable at the Grade 1 level; only absolute hemoglobin will be used to 
define Grade 1. 
• Severity grading for Grade 4 local reaction to injectable product (Erythema/Redness and 
Induration/Swelling) refer to necrosis or exfoliative dermatitis “requiring medical 
attention.” 
• Bruising or skin lesion associated with study injection will be assessed using the same 
severity grading as for erythema/redness. 

 
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When not otherwise specified, the following guidance will be used to assign a severity grade: 
• Grade 1 (Mild): No effect on activities of daily living 
• Grade 2 (Moderate): Some interference with activity not requiring medical intervention 
• Grade 3 (Severe): Prevents daily activity and requires medical intervention  
• Grade 4 (Potentially Life-threatening): Hospitalization; immediate medical 
intervention or therapy required to prevent death. 
• Grade 5 (Death): Death is assigned a Grade 5 severity. Only the single AE that is 
assessed as the primary cause of death should be assigned “Grade 5” severity. 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials 
Modified from FDA Guidance - September 2007 
A. Tables for Clinical Abnormalities  
Local Reaction to 
Injectable Product  
Mild 
 (Grade 1)  
Moderate 
(Grade 2)  
Severe  
(Grade 3)  
Potentially Life 
Threatening  
(Grade 4) 
Pain 
Does not 
interfere  
with activity  
Repeated use of 
non-narcotic pain 
reliever > 24 hours 
or interferes with 
activity 
Any use of 
narcotic pain 
reliever or prevents 
daily  
activity 
Hospitalization 
Tenderness 
Mild discomfort 
to touch 
Discomfort 
with 
movement 
Significant 
discomfort at rest  
Hospitalization 
1,2Erythema/Redness   
2.5 – 5 cm 
5.1 – 10 cm  
> 10 cm 
Necrosis or 
exfoliative 
dermatitis 
requiring 
medical 
attention  
3Induration/Swelling  
2.5 – 5 cm and 
does not interfere  
with activity  
5.1 – 10 cm or 
interferes with  
activity  
> 10 cm or  
prevents daily  
activity  
Necrosis 
requiring 
medical 
attention  
*Axillary (underarm) 
swelling or tenderness 
ipsilateral to the site of 
injection 
Does not 
interfere  
with activity 
Repeated use of 
non-narcotic pain 
reliever > 24 hours 
or interferes with 
activity 
Any use of 
narcotic pain 
reliever or prevents 
daily  
activity
Hospitalization 
* Added to the FDA guidance to collect lymphadenopathy symptoms 

 
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4 Vital Signs 
Mild  
(Grade 1)  
Moderate 
(Grade 2)  
Severe  
(Grade 3)  
Potentially 
Life  
Threatening  
(Grade 4)  
5Fever (°C)  
            (°F)  
38.0 – 38.4  
100.4 – 101.1  
38.5 – 38.9  
101.2 – 102.0  
39.0 – 40  
102.1 – 104  
> 40  
> 104  
Tachycardia - beats 
per  
minute 
 
101 – 115  
116 – 130  
> 130  
Hospitalization 
for arrhythmia  
6Bradycardia - beats 
per Minute 
50 – 54  
45 – 49  
< 45  
Hospitalization 
for arrhythmia  
Hypertension 
(systolic) - mm Hg  
141 – 150  
151 – 155  
> 155  
Hospitalization 
for malignant  
hypertension  
Hypertension 
(diastolic) - mm Hg  
91 – 95  
96 – 100  
> 100  
Hospitalization 
for malignant  
hypertension  
Hypotension 
(systolic) – mm Hg  
85 – 89  
80 – 84  
< 80  
Hospitalization 
for hypotensive 
shock  
Respiratory Rate – 
breaths per minute  
17 – 20  
21 – 25  
> 25  
Intubation  
1In addition to grading the measured local reaction at the greatest single diameter, the measurement 
should be recorded as a continuous variable.  
2Bruising or skin lesion associated with study injection will be assessed using the same severity grading 
as for erythema/redness. 
3Induration/Swelling should be evaluated and graded using the functional scale as well as the actual 
measurement. 
4Subject should be at rest for all vital sign measurements.  
5Oral temperature; no recent hot or cold beverages or smoking.  
6When resting heart rate is between 60 – 100 beats per minute. Use clinical judgment when characterizing 
Bradycardia among some healthy subject populations, for example, conditioned athletes. 
 
 

 
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Systemic 
(General)  
Mild  
(Grade 1)  
Moderate 
(Grade 2)  
Severe  
(Grade 3)  
Potentially Life  
Threatening  
(Grade 4)  
Nausea/vomiting  
No interference  
with activity or 1 – 
2  
episodes/24 hours  
Some 
interference  
with activity or > 
2  
episodes/24 
hours  
Prevents daily  
activity, requires  
outpatient IV  
hydration  
Hospitalization 
for hypotensive 
shock  
Diarrhea  
2 – 3 loose stools 
or 
< 400 gms/24 
hours 
4 – 5 stools or  
400 – 800 
gms/24  
hours  
6 or more watery  
stools or  
> 800gms/24 
hours or requires  
outpatient IV  
hydration  
Hospitalization  
Headache  
No interference 
with activity  
Repeated use of 
non-narcotic 
pain  
reliever > 24 
hours or some 
interference  
with activity  
Significant; any  
use of narcotic  
pain reliever or  
prevents daily  
activity  
Hospitalization  
Fatigue  
No interference 
with activity  
Some 
interference  
with activity  
Significant;  
prevents daily  
activity  
Hospitalization  
Myalgia  
No interference 
with activity  
Some 
interference  
with activity  
Significant;  
prevents daily  
activity  
Hospitalization  
Illness or clinical 
adverse  
event (as defined  
according to 
applicable  
regulations)  
No interference 
with activity  
Some 
interference  
with activity not  
requiring 
medical  
intervention  
Prevents daily  
activity and  
requires medical  
intervention  
Hospitalization  

 
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B. Tables for Laboratory Abnormalities  
The laboratory values provided in the tables below serve as guidelines and are dependent upon 
the institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate. 
Serum*  
Mild  
(Grade 1)  
Moderate  
(Grade 2)  
Severe  
(Grade 3)  
Potentially Life  
Threatening  
(Grade 4) ** 
Sodium – Hyponatremia 
mEq/L 
132 – 134  
130 – 131  
125 – 129  
< 125  
Sodium – Hypernatremia 
mEq/L 
144 – 145  
146 – 147  
148 – 150  
> 150  
Potassium – Hyperkalemia 
mEq/L 
5.1 – 5.2  
5.3 – 5.4  
5.5 – 5.6  
> 5.6  
Potassium – Hypokalemia 
mEq/L 
3.5 – 3.6  
3.3 – 3.4  
3.1 – 3.2  
< 3.1  
Glucose – Hypoglycemia 
mg/dL  
65 – 69  
55 – 64  
45 – 54  
< 45  
Glucose – Hyperglycemia  
Fasting – mg/dL  
Random – mg/dL  
 
100 – 110  
110 – 125  
 
111 – 125  
126 – 200  
 
>125  
>200  
Insulin 
requirements or 
hyperosmolar 
coma  
Blood Urea Nitrogen  
BUN mg/dL  
23 – 26  
27 – 31  
> 31  
Requires dialysis  
Creatinine – mg/dL  
1.5 – 1.7  
1.8 – 2.0  
2.1 – 2.5  
> 2.5 or requires 
dialysis  
Calcium – hypocalcemia 
mg/dL  
8.0 – 8.4  
7.5 – 7.9  
7.0 – 7.4  
< 7.0  
Calcium – hypercalcemia 
mg/dL  
10.5 – 11.0  
11.1 – 11.5  
11.6 – 12.0  
> 12.0  
Magnesium – 
hypomagnesemia mg/dL  
1.3 – 1.5  
1.1 – 1.2  
0.9 – 1.0  
< 0.9  
Phosphorous – 
hypophosphatemia mg/dL  
2.3 – 2.5  
2.0 – 2.2  
1.6 – 1.9  
< 1.6  
CPK – mg/dL  
1.25 – 1.5 x 
ULN***  
>1.5 – 3.0 x 
ULN  
>3.0 –10 x 
ULN  
> 10 x ULN  
Albumin – 
Hypoalbuminemia g/dL  
2.8 – 3.1  
2.5 – 2.7  
< 2.5  
--  
Total Protein – 
Hypoproteinemia g/dL  
5.5 – 6.0  
5.0 – 5.4  
< 5.0  
--  
Alkaline phosphate –  
increase by factor  
1.1 – 2.0 x 
ULN  
2.1 – 3.0 x 
ULN  
> 3.0 – 10 x 
ULN  
> 10 x ULN  

 
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Serum*  
Mild  
(Grade 1)  
Moderate  
(Grade 2)  
Severe  
(Grade 3)  
Potentially Life  
Threatening  
(Grade 4) ** 
Liver Function Tests –
ALT, AST increase by 
factor  
1.1 – 2.5 x 
ULN  
> 2.6 – 5.0 x 
ULN  
> 5.1 – 10 x 
ULN  
> 10 x ULN  
Bilirubin – when 
accompanied by any 
increase in Liver Function 
Test  
increase by factor  
1.1 – 1.25 x 
ULN  
> 1.26 – 1.5 x 
ULN  
> 1.51 – 
1.75 x ULN  
> 1.75 x ULN  
Bilirubin – when Liver 
Function Test is normal; 
increase by factor  
1.1 – 1.5 x 
ULN  
1.6 – 2.0 x 
ULN  
2.0 – 3.0 x 
ULN  
> 3.0 x ULN  
Cholesterol  
201 – 210  
211 – 225  
> 226  
---  
Pancreatic enzymes – 
amylase, lipase  
1.1 – 1.5 x 
ULN  
1.6 – 2.0 x 
ULN  
2.1 – 5.0 x 
ULN  
> 5.0 x ULN  
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional 
normal parameters. Institutional normal reference ranges should be provided to demonstrate that they are 
appropriate. 
** The clinical signs or symptoms associated with laboratory abnormalities might result in 
characterization of the laboratory abnormalities as Potentially Life Threatening (Grade 4). For example, a 
low sodium value that falls within a Grade 3 parameter (125-129 mE/L) should be recorded as a Grade 4 
hyponatremia event if the subject had a new seizure associated with the low sodium value. 
***ULN is the upper limit of the normal range. 
 
 
 

 
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Hematology *  
Mild  
(Grade 1)  
Moderate  
(Grade 2)  
Severe  
(Grade 3)  
Potentially Life  
Threatening 
(Grade 4)  
Hemoglobin (Female) - 
gm/dL  
11.0 – 12.0  
9.5 – 10.9  
8.0 – 9.4  
< 8.0  
Hemoglobin (Female)  
decrease from baseline 
value - gm/dL  
not 
applicable 
1.6 – 2.0  
2.1 – 5.0  
> 5.0  
Hemoglobin (Male) - 
gm/dL  
12.5 – 13.5  
10.5 – 12.4  
8.5 – 10.4  
< 8.5  
Hemoglobin (Male)  
decrease from baseline 
value – gm/dL  
not 
applicable  
1.6 – 2.0  
2.1 – 5.0  
> 5.0  
WBC Increase - cell/mm
3 
10,800 – 
15,000  
15,001 – 
20,000  
20,001 – 25, 
000  
> 25,000  
WBC Decrease - cell/mm
3 
2,500 – 
3,500  
1,500 – 2,499  
1,000 – 
1,499  
< 1,000  
Lymphocytes Decrease - 
cell/mm
3 
750 – 1,000  500 – 749  
250 – 499  
< 250  
Neutrophils Decrease - 
cell/mm
3 
1,500 – 
2,000  
1,000 – 1,499  
500 – 999  
< 500  
Eosinophils - cell/mm
3 
650 – 1500  
1501 - 5000  
> 5000  
Hypereosinophilic  
Platelets Decreased - 
cell/mm
3 
125,000 – 
140,000  
100,000 – 
124,000  
25,000 – 
99,000  
< 25,000  
PT – increase by factor  
(prothrombin time)  
1.10 x 
ULN**  
> 1.11 – 1.20 x 
ULN  
1.21 – 1.25 
x ULN  
> 1.25 ULN  
PTT – increase by factor 
(partial thromboplastin 
time)  
1.10 – 1.20 
x ULN  
1.21 – 1.4 x 
ULN  
1.4 – 1.5 x 
ULN  
> 1.5 x ULN  
Fibrinogen increase - 
mg/dL  
400 – 500  
501 – 600  
> 600  
--  
Fibrinogen decrease - 
mg/dL  
150 – 200  
125 – 149  
100 – 124  
< 100 or 
associated with 
gross bleeding  
or disseminated 
intravascular 
coagulation (DIC)  
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional 
normal parameters. Institutional normal reference ranges should be provided to demonstrate that they are 
appropriate. 
**ULN is the upper limit of the normal range. 

 
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APPENDIX III: ADVERSE EVENTS OF SPECIAL INTEREST TERMS
 
 

 
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Investigators should report all events that fall into the categories presented in Table 6 as an AESI 
per the reporting processes in Section 5.4. These AESIs are medical concepts that are generally 
of interest in vaccine safety surveillance as per the Brighton Collaboration and Safety Platform 
for Emergency Vaccines Adverse Events of Special Interest. 
Table 6: AESI Categories 
Medical Concept 
Additional Notes 
Thrombocytopenia 
• Decreased platelet count that is clinically 
significant as determined by the PI or designee  
Including but not limited to immune 
thrombocytopenia, platelet production decreased, 
thrombocytopenic purpura, thrombotic 
thrombocytopenic purpura, or hemolysis, elevated 
liver enzymes, and low platelet count (HELLP) 
syndrome 
New onset of or worsening of the 
following neurologic diseases: 
• Guillain Barre Syndrome 
• Acute disseminated encephalomyelitis (ADEM) 
• Idiopathic peripheral facial nerve palsy (Bell’s 
palsy) 
• Seizures including but not limited to febrile 
seizures and/or generalized seizures/convulsions 
Anaphylaxis 
• Anaphylaxis as defined per protocol 
• Follow reporting procedures in Section 5.4 
Myocarditis/Pericarditis 
• Myocarditis 
• Pericarditis 
• Myopericarditis 
 
 
 

 
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Table 7: Case Definitions of Probable and Confirmed Myocarditis, Pericarditis, and 
Myopericarditis 
Condition 
Definition 
Acute 
myocarditis 
Probable case 
Confirmed case 
Presenceof≥ 1 new or worsening 
of the following clinical 
symptoms:* 
Presenceof≥ 1 new or worsening of 
the following clinical symptoms:* 
• chest pain, pressure, or 
discomfort 
• chest pain, pressure, or 
discomfort 
• dyspnea, shortness of breath, 
or pain with breathing 
• dyspnea, shortness of breath, or 
pain with breathing 
• palpitations 
• palpitations 
• syncope 
• syncope 
AND 
AND 
≥ 1 new finding of 
≥ 1 new finding of 
• troponin level above upper 
limit of normal (any type of 
troponin) 
• histopathologic confirmation of 
myocarditis† 
• abnormal electrocardiogram 
(ECG or EKG) or rhythm 
monitoring findings 
consistent with myocarditis§ 
• abnormal cardiac function or 
wall motion abnormalities on 
echocardiogram 
• cMRI findings consistent with 
myocarditis¶ in the presence of 
troponin level above upper limit 
of normal (any type of troponin) 
• cMRI findings consistent 
with myocarditis¶ 
AND 
AND 
• No other identifiable cause 
of the symptoms and 
findings 
• No other identifiable cause of the 
symptoms and findings 
Acute 
pericarditis** 
Presenceof≥ 2 new or worsening of the following clinical features: 
• acute chest pain†† 
• pericardial rub on exam 
• new ST-elevation or PR-depression on EKG 
• new or worsening pericardial effusion on echocardiogram or MRI 
Myopericarditis 
 
This term may be used for patients who meet criteria for both myocarditis 
and pericarditis. 

 
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Abbreviations: AV = atrioventricular; cMRI = cardiac magnetic resonance imaging; ECG or 
EKG = electrocardiogram. 
 
 * Persons who lack the listed symptoms but who meet other criteria may be classified as subclinical 
myocarditis (probable or confirmed). 
 † Using the Dallas criteria [47]. Autopsy cases may be classified as confirmed clinical myocarditis on the 
basis of meeting histopathologic criteria if no other identifiable cause. 
 § To meet the ECG or rhythm monitoring criterion, a probable case must include at least one of 1) ST-
segment or T-wave abnormalities; 2) Paroxysmal or sustained atrial, supraventricular, or ventricular 
arrhythmias; or 3) AV nodal conduction delays or intraventricular conduction defects. 
 ¶ Using either the original or the revised Lake Louise criteria [49].  
**[50]  
 †† Typically described as pain made worse by lying down, deep inspiration, or cough, and relieved by 
sitting up or leaning forward, although other types of chest pain might occur [48]. 

PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 12/20/2023 V4.0
Page 1 of 15
CC ICF template v9 04.13.2021
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
PRINCIPAL INVESTIGATOR:  Lesia Dropulic, MD
STUDY TITLE: VRC 322/DMID 21-0016: A Phase I, Dose Escalation, Open-Label Clinical 
Trial to Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV) mRNA 
Vaccine, mRNA-1215, in Healthy Adults
STUDY SITE: NIH/NIAID/VRC/Vaccine Evaluation Clinic (VEC)
Cohort: Healthy volunteer 
Consent Version:  Version 4.0, December 20, 2023
WHO DO YOU CONTACT ABOUT THIS STUDY? 
Principal Investigator: Lesia Dropulic, MD; 
Study Coordinator: Laura Novik, RN, MA, CCRC;
KEY INFORMATION ABOUT THIS RESEARCH 
This consent form describes a research study and is designed to help you decide if you would 
like to be a part of the research study.  
You are being asked to take part in a research study at the National Institutes of Health (NIH). 
This study is being conducted by the Vaccine Research Center (VRC) and is sponsored by the 
Division of Microbiology and Infectious Diseases (DMID). This section provides the 
information we believe is most helpful and important to you in making your decision about 
taking part in this study. Additional information that may help you decide can be found in other 
sections of the document. Taking part in research at the NIH is your choice.
This is a study of an experimental vaccine called mRNA-1215 for prevention of the Nipah virus 
(NiV) infection. The experimental vaccine is a messenger ribonucleic acid (mRNA) vaccine, 
made of the genetic code of the virus. This genetic code will make a protein from the virus and 
cause your body to think you have been infected with the virus. It is not made from the Nipah 
virus and cannot cause Nipah virus infection. This study vaccine has not been given to humans 
before this study.
The main purpose of this study is to see if the experimental vaccine is safe and how your body 
responds to it.  Since this is the first time we are giving mRNA-1215 to people, we do not know 
how your body will respond. This study is not designed to protect you from Nipah virus 
infection.
Nipah virus is transmitted from animals to humans, from human to human and through 
contaminated food. In infected people, the virus causes mild to severe illness. Some people have 
no symptoms, some may have respiratory illness, such as cough and difficulty breathing. People 
with severe symptoms may have brain swelling which can lead to death. Although Nipah virus 
has caused only a few known outbreaks in Asia, it infects a wide range of animals and can cause 
IRB NUMBER: 000687
IRB EFFECTIVE DATE: 12/28/2023

PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 12/20/2023 V4.0
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CC ICF template v9 04.13.2021
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
severe disease and death in people, making it a public health concern. There are currently no 
drugs or vaccines to treat or prevent Nipah virus infection.
About 40 people will take part in this study at the Vaccine Evaluation Clinic (VEC) in the NIH 
Clinical Center in Bethesda, MD. You will be in the study for about 56 weeks (14 months). You 
will have about 13 clinic visits during the study. At each clinic visit, you will have about 3 to 14 
tubes of blood drawn. Some of your blood will be stored for future research. You will be 
compensated for your time and efforts for taking part in this study.
You will get 2 doses of the experimental mRNA-1215 vaccine during this study, 1 month apart. 
The injection (shot) will be given in the upper arm muscle. This is called an intramuscular “IM” 
injection. We will use a needle and syringe to give you the injection.
You may have side effects from the mRNA-1215 vaccine, such as feeling tired/unwell, fever, 
muscle aches, headache, chills, nausea, joint pain or injection site reactions including 
pain/tenderness, redness, swelling, itchiness at the injection site, and lymph node swelling on 
the same side as the injection. These side effects also commonly occur with FDA approved 
vaccines. The side effects usually occur within the first 24 hours after the vaccine is given. 
Rarely, a serious allergic reaction with symptoms like hives, rash, sweating, swelling around the 
mouth, throat or eyes, wheezing, trouble breathing, increased pulse or sudden weakness may 
occur shortly after any vaccination. This is called “anaphylaxis” and may be life threatening. 
Rare cases of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of 
the lining around the heart) have been reported in individuals after they received a similar 
mRNA-based vaccine against COVID-19. 
We do not know how the experimental vaccine may affect a fetus or nursing infant. Therefore, 
women who can become pregnant must have a negative pregnancy test before each injection 
and must agree to use effective birth control beginning at least 21 days before the first 
vaccination until the end of the study.
The remaining document will now describe the research study in more detail.  This information 
should be considered before you make your choice. Members of the study team will talk with you 
about the information in this document. Some people have personal, religious, or ethical beliefs 
that may limit the kinds of medical or research interventions in which they would want to 
participate. Take the time you need to ask any questions and discuss this study with NIH staff, and 
with your family, friends, and personal health care providers.
IT IS YOUR CHOICE TO TAKE PART IN THE STUDY
You may choose not to take part in this study for any reason. If you join this study, you may change 
your mind and stop participating in the study at any time and for any reason. In either case, you 
will not lose any benefits to which you are otherwise entitled. However, to be seen at the NIH, you 
must be taking part in a study or are being considered for a study. If you do choose to leave the 
study, please inform your study team to ensure a safe withdrawal from the research.  
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WHY IS THIS STUDY BEING DONE?
Nipah virus is transmitted from animals to humans, from human to human and through 
contaminated food. In infected people, the virus causes mild to severe illness. Some people have 
no symptoms, some may have respiratory illness, such as cough and difficulty breathing. People 
with severe symptoms may have brain swelling which can lead to death. Although Nipah virus has 
caused only a few known outbreaks in Asia, it infects a wide range of animals and can cause severe 
disease and death in people, making it a public health concern. There are currently no drugs or 
vaccines to treat or prevent Nipah virus infection.
This is a study of an experimental vaccine called mRNA-1215 for prevention of the Nipah virus 
(NiV) infection. The experimental vaccine is a messenger ribonucleic acid (mRNA) vaccine made 
by Moderna. This study vaccine is made of the genetic code of the virus. This genetic code will 
make a protein from the virus and cause your body to think you have been infected with the virus. 
It is not made from the Nipah virus and cannot cause Nipah virus infection. This study vaccine has 
not been given to humans before this study.
The main purpose of this study is to see if the experimental vaccine is safe and how your body 
responds to it.  Since this is the first time we are giving mRNA-1215 to people, we do not know 
how your body will respond. This study is not designed to protect you from Nipah virus. We will 
tell you if we learn anything new during this study that might cause you to change your mind about 
staying in the study. At the end of the study, we will tell you when study results may be available 
and how to learn about them.
We are asking you to join this research study because you are a healthy adult and qualify for 
participation based on screening evaluations. 
The mRNA-1215 vaccine is an investigational product, which means that it has not been approved 
by the U.S. Food and Drug Administration (FDA) to use for prevention of NiV infection. The FDA 
allows this experimental product to be used for research only. 
WHAT WILL HAPPEN DURING THE STUDY?
The table below shows the plan for this study. 
Study Plan
Group
Number of 
Participants
Dose/Route
Day 0
Month 1
1
10
25 mcg IM
X
X
2
10
50 mcg IM
X
X
3
10
100 mcg IM
X
X
4
10
10 mcg IM
X
X
Total 
40
If you decide to take part in this study, you will be asked to review and agree to this informed 
consent form and the procedures it describes. You will have completed the screening process 
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which includes a physical exam and review of your medical history, vital signs and laboratory 
results, including an HIV test. You must be healthy and qualify for enrollment before you can take 
part in this study.
The study opened with enrollments into Group 1 for the 25 mcg mRNA-1215 dose.  After the 
study team agreed that there were no safety concerns with the vaccine, Group 2 and Group 3 
opened. The dose for Group 4 was selected based on the data from Groups 1-3. At this time, all 
new enrollments will be assigned to Group 4 because Groups 1-3 have already been filled.
If you are female and able to become pregnant, you must use an effective method of birth control 
for the entire study, beginning 21 days prior to enrollment. You will be given a pregnancy test 
before each vaccination. If you are pregnant, we will not give you mRNA-1215.
Vaccine Administration 
The injection (shot) will be given in the upper arm muscle. This is called an intramuscular “IM” 
injection. We will use a needle and syringe to give you the injection.
You will need to stay in the clinic for at least 30 minutes after each vaccination. You may need to 
stay longer than 30 minutes if you feel unwell or have symptoms. In keeping with the NIH CC 
policy and good medical practice, medical care will be given to subjects for any immediate allergic 
reactions or other injury resulting from participation in this research study.
Follow-Up after Vaccination
The day after your vaccination, clinic staff will call to check on you. Also, after each vaccination, 
you will need to complete a diary card. You will need to record any symptoms that you may have 
as a result of the vaccination on the diary card for 7 days. We will give you a thermometer to check 
your temperature every day. You will need to check your temperature and complete your diary 
card even if you feel well and have no symptoms. We will also give you a ruler to measure any 
skin changes at the injection site. You will get a password to a secure website where you can enter 
this data online. If you do not have access to the internet, you can use a paper diary card instead. 
If you have any symptoms or feel unwell at any time during the study, you should tell a clinic 
nurse or doctor as soon as possible. You can reach the staff by phone 24 hours a day. If you have 
symptoms, you may be asked to come to the clinic for a checkup. It is very important that you 
follow the instructions from the clinic staff. 
You will have several follow-up visits during this study. These visits allow us to check you for 
any health changes or problems. We will ask you how you are feeling and if you have taken any 
medications.
We will draw about 3 to 14 tubes or 28 to 136 mL (about 2 to 9 tablespoons) of blood at each 
follow-up visit. In keeping with NIH Clinical Center guidelines, we will not draw more than 550 
mL of blood from you in any 8-week period. Some of the blood that we take will be used for 
research and some will be used to monitor your health. We will tell you right away if any of the 
tests done to monitor your health show a problem. You might need to have extra clinic visits or 
laboratory tests if you have health changes that need to be checked. 
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Clinical studies follow a set schedule. It is important that you follow the schedule as closely as 
possible. You should try to not miss any visits. You should contact the clinic staff as soon as 
possible if you need to change the date or time of any study visit. 
Genetic Testing
Some of the blood drawn from you for research purposes will be used for genetic tests. Some 
genetic tests are done in research studies to see if there are genetic differences in immune 
responses. Your blood samples used in these genetic tests will not have your name on it, and the 
results will not be in your medical record. You will not get results of these tests. 
Apheresis
We would like to collect your blood one time by a method called “apheresis” at 2 weeks after your 
second vaccination. This procedure is optional and choosing not to take part will not affect your 
study participation. To be eligible for apheresis, you must not: 

have an unstable heart as indicated by your medical history and test results

have blood pressure greater than 180/100

have a known blood clotting disorder 

be pregnant or breast feeding 

have a condition that the attending physician or the apheresis clinic staff considers a reason 
to not do an apheresis procedure. 
Before apheresis, we will check your weight, pulse and blood pressure. We will ask questions 
about your general health and medical history. If you are female and able to become pregnant, we 
will do a pregnancy test before the apheresis procedure. The test must show that you are not 
pregnant. The apheresis staff will prick your finger to test your blood for anemia before the 
procedure. 
During the procedure, you will lay on a reclining chair or hospital bed. A sterile needle will be 
placed into a vein in both of your arms. The kits used to collect apheresis samples are sterile, 
single-use, disposable sets that are not in contact with any person’s bodily fluids other than yours. 
No blood products are given to you during the procedure. Apheresis is done at the NIH Clinical 
Center, and a physician from the NIH Department of Transfusion Medicine will be available in or 
near the apheresis area at all times. 
In the apheresis procedure, blood is removed through a needle in the vein of one arm, spun in a 
machine that separates the white blood cells and then the rest of your blood is returned to you 
through a needle in the other arm. A medication called Citrate is added to the blood while in the 
machine to prevent your blood from clotting. 
The purpose of this procedure is to allow us to get a large number of white blood cells that cannot 
be collected by simple blood drawing. We want to study these white blood cells. The number of 
white blood cells collected is a small fraction of the total amount in your body. The body quickly 
replaces the cells that have been removed. The NIH Blood Bank at the Clinical Center and other 
blood banks use similar procedures every day to collect blood samples from donors. We will not 
use your samples for transfusion or therapy.
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HOW LONG WILL THE STUDY TAKE?
If you agree to take part in this study, your involvement is expected to last for 52 weeks (1 year) 
after your last vaccination. 
Participants in all groups will have a total of 2 vaccination visits, 11 follow-up clinic visits, and 2 
follow-up phone calls over 56 weeks. Each vaccination visit will take about 6 hours. Most other 
follow-up clinic visits will take about 1 to 2 hours. The optional apheresis visit will take 3 to 4 
hours. 
HOW MANY PEOPLE WILL PARTICIPATE IN THIS STUDY?
We plan to enroll about 40 people in this study. This includes 10 people in the 25 mcg dose 
group, 10 people who in the 50 mcg dose group, 10 people in the 100 mcg dose group, and 10 
people who will get the 10 mcg  dose.  
WHAT ARE THE RISKS AND DISCOMFORTS OF BEING IN THE STUDY?
Possible Risks of the mRNA-1215 vaccine 
The mRNA-1215 vaccine has not been given to people before this study. It may have unknown 
risks. It has been tested in animals. The vaccine did not cause any unusual side effects in animals 
and met the safety criteria to be tested in humans. 
You may experience any of the following: feeling tired/unwell, fever, muscle aches, headache, 
chills, nausea, joint pain, or injection site reactions including pain/tenderness, redness, swelling, 
itchiness at the injection site, and lymph node swelling. These side effects also commonly occur 
with FDA approved vaccines. The side effects usually occur within the first 24 hours after the 
vaccine is given and go away within a few days to a week. 
Rarely, a serious allergic reaction with symptoms like hives, rash, sweating, swelling around the 
mouth, throat or eyes, wheezing, trouble breathing, increased pulse or sudden weakness may 
occur shortly after any vaccination. This is called “anaphylaxis” and may be life threatening. 
While you are waiting in the clinic after vaccination, we will monitor you for anaphylaxis. 
Treatment for anaphylaxis will be given right away if it occurs. Also rarely, hives may occur 
after any vaccination and may last for days to several months. If you have hives, we will treat 
you and monitor you frequently.
Recently, rare cases of myocarditis (inflammation of the heart muscle) and pericarditis 
(inflammation of the lining around the heart) have been reported in males and females after they 
received the COVID-19 mRNA vaccines. Most of the cases of myocarditis or pericarditis 
happened in males and females shortly after the second dose of the vaccine. The risk was highest 
in males under the age of 40, specifically males between 12 and 17 years old.
Symptoms of myocarditis or pericarditis include:

Chest pain

Shortness of breath

Feelings of having a fast-beating, fluttering, or pounding heart 
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These symptoms start most commonly within a few days after study vaccination. You should seek 
medical attention and also notify study staff if you have any of these symptoms. Although some 
people who had myocarditis or pericarditis had a severe case, most people felt better quickly. Long 
term follow-up information on these rare situations is limited at this time. We do not know if the 
risk of myocarditis or pericarditis may be increased following additional doses of the vaccine.
Possible Risks of Vaccine Injections 
Temporary stinging, pain, redness, soreness, itchiness, swelling, or bruising may occur at the site 
of the injection.
Possible Risks of Blood Drawing 
Blood drawing may cause pain, bruising, and lightheadedness or fainting. Very rarely, an 
infection at the site where the blood is taken may occur.
Possible Risks of Apheresis 
Apheresis is generally safe, and side effects are rare. Pain, bruising or discomfort at the needle 
placement site may occur. Sometimes apheresis causes a tingling sensation around the lips, nose 
and mouth, feeling chilled, and/or slight nausea. This can usually be relieved by slowing or 
temporarily stopping the apheresis or taking a calcium pill, like Tums®. Other possible side 
effects are anxiety, vomiting, and lightheadedness. Temporary lowering of the blood pressure 
may develop. There is the rare possibility of infection, fainting, or seizure. Very rarely a nerve 
problem at the needle placement site may occur. Also, very rarely, a machine malfunction may 
occur and result in the loss of about one unit (one pint) of blood. 
There are theoretical risks from re-infusion of the blood after processing by the machine such as 
infection or an adverse reaction to the blood components. However, this has not been seen in 
many thousands of volunteers who have undergone this or similar procedures to date. There may 
be other risks of apheresis that are unknown at this time. 
During the procedure, your platelet count may decrease because platelets are collected with the 
white blood cells. Platelets are cells that help your blood to clot. Taking aspirin in combination 
with a lowered platelet count may increase your chance of developing bleeding. Therefore, you 
should not take aspirin or aspirin-containing drugs for 2 weeks after the procedure without 
physician approval.
Unknown Safety Risks
There may be side effects from the study vaccine - even serious or life-threatening ones - that 
we do not yet know about. Please tell the study staff about any side effect you think you are 
having. This is important for your safety.
Possible Risks from Stored Samples 
We will collect blood samples from you during the study. We will keep these samples 
indefinitely for future research to learn more about flu virus, vaccines, the immune system, and 
other research questions. Results from research with your samples will not be in your medical 
record or reported to you. 
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Labeling of Stored Samples: Your stored samples will be labeled by a special code or number 
and not your personal information. Only the study team can link this code to you. Any identifying 
information about you (like name or date of birth) will be kept as confidential as allowed by law. 
Risks of Stored Samples: There is a small chance that information from your medical records 
could be given to someone who should not get it without your permission. It is possible for 
someone to use that information to discriminate against you when you apply for insurance or 
employment. Similar problems may occur if you give information about yourself or agree to 
have your medical records released. 
Possible Risks of Data Sharing 
Information in the shared databases could be linked back to you and used to discriminate against 
you or your family. State and federal laws provide some protections against genetic and 
preexisting conditions discrimination. 
Possible Other Risks 
We do not know if the study vaccine will change how your body responds to Nipah virus 
infections in the future. You may not donate blood at a blood bank while taking part in this study. 
You may not donate blood for one year after the last experimental vaccine injection.
What are the risks related to pregnancy? 
We do not know how the experimental vaccine may affect a fetus or nursing infant. Therefore, 
women who are able to become pregnant must have a negative pregnancy test before each vaccine 
injection and must agree to use effective birth control beginning at least 21 days before the first 
injection until the end of the study. We will discuss effective methods of birth control with you. 
Any time during the study you must tell the clinic staff right away if you become pregnant, your 
birth control method fails, or you think that you might be pregnant. If you are pregnant, you will 
be asked to continue with follow-up visits so that we can check your health. We will contact you 
to ask about the outcome of the pregnancy.
WHAT ARE THE BENEFITS OF BEING IN THE STUDY?
You will not benefit from being in this study.
Are there any potential benefits to others that might result from the study?
In the future, other people might benefit from this study because of knowledge we gain about 
vaccines and immune responses against Nipah virus. 
WHAT OTHER OPTIONS ARE THERE FOR YOU?
Before you decide whether or not to be in this study, we will discuss other options that are 
available to you. Instead of being in this study, you could choose not to take part. You may be 
eligible for other VRC studies.
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DISCUSSION OF FINDINGS
New information about the study
If we find out any new information that may affect your choice to participate in this study, we 
will get in touch with you to explain what we have learned. This may be information we have 
learned while doing this study here at the NIH or information we have learned from other 
scientists doing similar research in other places.
Return of research results
At each visit you will be checked for any health changes or problems. Blood will be drawn at 
almost every study visit to check on your health. You will be informed right away if any of your 
test results show a health problem. The results of this study may be reported in medical journals, 
on the internet or at scientific meetings. We will give you information about how to find the study 
results once they are available.
EARLY WITHDRAWAL FROM THE STUDY 
Your participation in this study is completely voluntary. You can choose to stop taking part in 
the study at any time. There is no penalty or loss of benefits if you choose to leave the study. 
However, if you get at least one dose of mRNA-1215 during this study, we encourage you to 
take part in safety follow-up. It is important that we continue to check your health.
You may be removed from the research study for any of the following reasons: 

You don't keep appointments or follow study procedures; 

You get a serious illness that needs ongoing medical care; 

The researcher believes that it is in your best interest to remove you from the study; 

The study is stopped by regulatory agencies, the study sponsor, or study investigators. If 
this happens, we will tell you why.
The study team may also decide to keep you in the study but to stop giving you study product. 
If you need a treatment with a medication that affects your immune system (such as a steroid 
like prednisone), please inform the study team as soon as possible. In this case, the second 
vaccine administration may be discontinued or delayed up to 2 weeks after the treatment. 
If you are not able to get the second injection or it is discontinued by the researchers, we may 
adjust your follow-up schedule but will ask that you still attend study visits. 
STORAGE, SHARING AND FUTURE RESEARCH USING YOUR SPECIMENS AND 
DATA
Will your specimens or data be saved for use in other research studies?
As part of this study, we are obtaining specimens and data from you. We will remove all the 
identifiers, such as your name, date of birth, address, or medical record number and label your 
specimens and data with a code so that you cannot easily be identified. However, the code will 
be linked through a key to information that can identify you. We plan to store and use these 
specimens and data for studies other than the ones described in this consent form that are going 
on right now, as well as studies that may be conducted in the future. These studies may provide 
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additional information that will be helpful in understanding Nipah virus, or other diseases or 
conditions. This could include studies to develop research tests, treatments, drugs, or devices, 
that may lead to the development of a commercial product by the NIH and/or its research or 
commercial partners. You will not be provided financial compensation if this happens. Also, it 
is unlikely that we will learn anything from these studies that may directly benefit you.
If you agree to take part in this study, you give permission for your coded specimens and data to 
be stored and used for future research as described above.
Will your specimens or data be shared for use in other future research studies?
We may share your coded specimens and data with other researchers.  If we do, while we will 
maintain the code key, we will not share it, so the other researchers will not be able to identify 
you.  They may be doing research in areas that are similar to this study or in other unrelated 
areas. These researchers may be at NIH, other research centers and institutions, or commercial 
entities.
By agreeing to take part in this study, you give permission for your coded specimens and data to 
be shared with other researchers and used by these researchers for future research as described 
above.
If you change your mind and do not want us to use your specimens and data for future research, 
you should contact the research team member identified at the top of this document. We will do 
our best to comply with your request but cannot guarantee it. For example, if research with your 
specimens and/or data has already been completed, the information from that research may still 
be used. Also, for example, if the specimens and data have been shared already with other 
researchers, it might not be possible to withdraw them.
In addition to the planned use and sharing described above, we might remove all identifiers and 
codes from your specimens and data and use or share them with other researchers for future 
research at the NIH or other places.  When we or the other researchers access your anonymized 
data, there will be no way to link the specimens or data back to you.  We will not contact you to 
ask your permission or otherwise inform you before we do this.  If we do this, we would not be 
able to remove your specimens or data to prevent their use in future research studies, even if you 
asked, because we will not be able to tell which are your specimens or data.
NIH policies require that your clinical and other study data be placed in an internal NIH database 
that is accessible to other NIH researchers for future research. Usually, these researchers will not 
have access to any of your identifiers, such as your name, date of birth, address, or medical 
record number; and your data will be labeled with only a code. We cannot offer you a choice of 
whether your data to be placed in this database or not.  If you do not wish to have your data 
placed in this database, you should not enroll in this study. 
If you decide not to take part in this study, you may still take part in other studies at NIH. 
How long will your specimens and data be stored by the NIH?
Your specimens and data may be stored by the NIH indefinitely.
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Risks of storage and sharing of specimens and data
When we store your specimens and data, we take precautions to protect your information from 
others that should not have access to it. When we share your specimens and data, we will do 
everything we can to protect your identity, for example, when appropriate, we remove 
information that can identify you. Even with the safeguards we put in place, we cannot guarantee 
that your identity will never become known, or someone may gain unauthorized access to your 
information. New methods may be created in the future that could make it possible to re-identify 
your specimens and data.
PAYMENT
Will you receive any type of payment for taking part in this study?
Some NIH Clinical Center studies offer compensation for participation in research. The amount of 
compensation, if any, is guided by NIH policies and guidelines. You will be compensated for your 
time and inconvenience by the NIH Clinical Research Volunteer Program. It is possible that you 
may have some expenses that are not covered by the compensation provided. 
The compensation is as follows: 

$315 per vaccination visit 

$25 total for the timely completion of all 7 days of an electronic diary 

$200 for each scheduled follow-up visit that includes a research blood draw 

$85 for all other clinic visits that do not include research blood draws 

$285 for optional apheresis
The total compensation you get is based on the number and type of study visits you complete. You 
will get the compensation about 2 weeks after each completed visit. You may choose to receive 
payments by direct deposit into a bank account or to an actual or digital debit card. If you are 
unable to finish the study, you will receive compensation only for the parts and visits you 
completed.
To receive compensation, you will be asked to provide your social security number. You can 
withhold your social security number and still participate in research, but you may not be able to 
receive compensation. With few exceptions, the NIH is required to report all payments given to 
research participants to the Internal Revenue Service (IRS). Study compensation is considered 
taxable income that is reportable to the Internal Revenue Service (IRS). A “Form 1099-Other 
Income” will be sent to you if your total payments for research participation are $600 or more in 
a calendar year. Payments are processed through the U.S. Treasury. If you have unpaid debt to the 
federal government, the U.S. Treasury may deduct all or some of your compensation. They will 
notify you directly if this happens.
REIMBURSEMENT
Will you receive reimbursement or direct payment by NIH as part of your participation?
This study does not offer reimbursement for participants, or payment of, hotel, travel, or meals.
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COSTS
Will taking part in this research study cost you anything?
NIH does not bill health insurance companies or participants for any research or related clinical 
care that you receive at the NIH Clinical Center. 
There are no costs to you for participating in this study. You or your health insurance will have to 
pay for all medical costs for medical care that you get outside this study. It is possible that you 
may have some expenses that are not covered by the study compensation provided.
CONFLICT OF INTEREST (COI)
The NIH reviews NIH staff researchers at least yearly for conflicts of interest.  This process is 
detailed in a COI Guide.  You may ask your research team for a copy of the COI Guide or for more 
information.  Members of the research team who do not work for NIH are expected to follow these 
guidelines or the guidelines of their home institution, but they do not need to report their personal 
finances to the NIH.
Moderna is providing mRNA-1215 for this study to NIH without charge. No NIH investigator 
involved in this study receives payments or other benefits from any company whose drug, product 
or device is being tested. However, there are some research partners not associated with the NIH 
working on this study who may receive payments or benefits, limited by the rules of their 
workplace. 
CLINICAL TRIAL REGISTRATION AND RESULTS REPORTING 
A description of this clinical trial will be available on www.ClinicalTrials.gov as required by U.S. 
Law. This website will not include information that can identify you. At most, the website will 
include a summary of the results. You can search this Web site at any time.
CONFIDENTIALITY PROTECTIONS PROVIDED IN THIS STUDY  
Will your medical information be kept private? 
We will do our best to make sure that the personal information in your medical record will be kept 
private.  However, we cannot guarantee total privacy.  Organizations that may look at and/or copy 
your medical records for research, quality assurance, and data analysis include:

The NIH and other government agencies, like the Food and Drug Administration (FDA), 
which are involved in keeping research safe for people.

National Institutes of Health Intramural Institutional Review Board

The study Sponsor (DMID) or their agent(s)

Qualified representatives from Moderna, the pharmaceutical company who produces 
mRNA-1215.
The researchers conducting this study and the NIH follow applicable laws and policies to keep 
your identifying information private to the extent possible.  However, there is always a chance 
that, despite our best efforts, your identity and/or information about your participation in this 
research may be inadvertently released or improperly accessed by unauthorized persons.
IRB NUMBER: 000687
IRB EFFECTIVE DATE: 12/28/2023

PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 12/20/2023 V4.0
Page 13 of 15
CC ICF template v9 04.13.2021
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
In most cases, the NIH will not release any identifiable information collected about you without 
your written permission.  However, your information may be shared as described in the section of 
this document on sharing of specimens and data, and as further outlined in the following sections.  
Further, the information collected for this study is protected by NIH under a Certificate of 
Confidentiality and the Privacy Act. 
Certificate of Confidentiality
To help us protect your privacy, the NIH Intramural Program has received a Certificate of 
Confidentiality (Certificate). With this certificate, researchers may not release or use data or 
information about you except in certain circumstances.  
NIH researchers must not share information that may identify you in any federal, state, or local 
civil, criminal, administrative, legislative, or other proceedings, for example, if requested by a 
court.  
The Certificate does not protect your information when it:  
1. is disclosed to people connected with the research, for example, information may be used 
for auditing or program evaluation internally by the NIH; or 
2. is required to be disclosed by Federal, State, or local laws, for example, when information 
must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA); 
3. is for other research;
4. is disclosed with your consent. 
The Certificate does not prevent you from voluntarily releasing information about yourself or your 
involvement in this research. 
The Certificate will not be used to prevent disclosure to state or local authorities of harm to self or 
others including, for example, child abuse and neglect, and by signing below you consent to those 
disclosures. Other permissions for release may be made by signing NIH forms, such as the Notice 
and Acknowledgement of Information Practices consent.
Privacy Act
The Federal Privacy Act generally protects the confidentiality of your NIH medical information 
that we collect under the authority of the Public Health Service Act.  In some cases, the Privacy 
Act protections differ from the Certificate of Confidentiality.  For example, sometimes the Privacy 
Act allows release of information from your record without your permission, for example, if it is 
requested by Congress. Information may also be released for certain research purposes with due 
consideration and protection, to those engaged by the agency for research purposes, to certain 
federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect 
reporting, to tumor registries, for quality assessment and medical audits, or when the NIH is 
involved in a lawsuit.  However, NIH will only release information from your medical record if it 
is permitted by both the Certificate of Confidentiality and the Privacy Act.
IRB NUMBER: 000687
IRB EFFECTIVE DATE: 12/28/2023

PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 12/20/2023 V4.0
Page 14 of 15
CC ICF template v9 04.13.2021
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
POLICY REGARDING RESEARCH-RELATED INJURIES  
The NIH Clinical Center will provide short-term medical care for any injury resulting from your 
participation in research here. In general, no long-term medical care or financial compensation for 
research-related injuries will be provided by the NIH, the NIH Clinical Center, or the Federal 
Government. However, you have the right to pursue legal remedy if you believe that your injury 
justifies such action.
PROBLEMS OR QUESTIONS
If you have any problems or questions about this study, or about your rights as a research 
participant, or about any research-related injury, contact the Principal Investigator, Lesia Dropulic, 
MD, 
 Other researchers you may call are: Laura Novik 
5. You may also call the NIH Clinical Center Patient Representative at 301-496-2626, 
or the NIH Office of IRB Operations at 301-402-3713, if you have a research-related complaint or 
concern.
CONSENT DOCUMENT 
Please keep a copy of this document in case you want to read it again.
IRB NUMBER: 000687
IRB EFFECTIVE DATE: 12/28/2023

PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 12/20/2023 V4.0
Page 15 of 15
CC ICF template v9 04.13.2021
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Adult Research Participant: I have read the explanation about this study and have been given the opportunity 
to discuss it and to ask questions. I consent to participate in this study.
Signature of Research Participant
Print Name of Research Participant
Date
Investigator:
Signature of Investigator
Print Name of Investigator
Date
Witness should sign below if either:
1. A short form consent process has been used to enroll a non-English speaking subject or
2. An oral presentation of the full consent has been used to enroll a blind or illiterate subject
Signature of Witness
Print Name of Witness
Date
NIH ADMINISTRATIVE SECTION TO BE COMPLETED REGARDING THE USE OF AN 
INTERPRETER:
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent and served as a witness. The investigator obtaining consent may not 
also serve as the witness.
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent but did not serve as a witness. The name or ID code of the person 
providing interpretive support is:
.
IRB NUMBER: 000687
IRB EFFECTIVE DATE: 12/28/2023