Revealing Protective Immunity to Influenza Using Systems Immunology
Phase: PHASE4
Conditions: Influenza
Sponsor: Emory University

Study Protocol 
 
 
 Revealing Protective Immunity to Influenza Using Systems Immunology 
(PRISM) 
 
 
Protocol Date: June 11, 2024 
 
 
NCT06501963 

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PROTOCOL TITLE:  Revealing protective immunity to influenza using systems immunology 
(PRISM)
EXTERNAL (NON-EMORY) COLLABORATORS                                                                   
Adriana Tomic, PhD
Depts. of Biomedical Engineering and Virology, Immunology & Microbiology
Boston University
PRINCIPAL INVESTIGATOR:
Daniel Graciaa, MD, MPH, MSc
Hope Clinic of the Emory Vaccine Center
Division of Infectious Diseases, Department of Medicine
Office Phone 
 
Cell Phone 
Email: 
VERSION: 1.0
FUNDING SOURCE: Boston University funds

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REVISION HISTORY
Revision #
Version 
Date
Summary of Changes

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Table of Contents
1.
Study Summary....................................................................................................................5
2.
Objectives ............................................................................................................................5
3.
Background..........................................................................................................................5
4.
Study Endpoints...................................................................................................................6
5.
Study Intervention/Investigational Agent ...........................................................................6
6.
Procedures Involved ............................................................................................................7
7.
Statistical Analysis Plan........................................................................................................7
8.
Data and/or Specimen Banking ...........................................................................................7
9.
Sharing of Results with Participants ....................................................................................8
10.
Study Timelines....................................................................................................................8
11.
Inclusion and Exclusion Criteria...........................................................................................8
12.
Population ...........................................................................................................................9
13.
Local Number of Participants ............................................................................................10
14.
Recruitment Methods........................................................................................................10
15.
Withdrawal of Participants................................................................................................11
16.
Risk to Participants ............................................................................................................11
17.
Potential Benefits to Participants......................................................................................11
18.
Compensation to Participants ...........................................................................................11
19.
Data Management and Confidentiality .............................................................................11
20.
Plans to Monitor the Data to Ensure Safety of Participants and Data Integrity................12
21.
Provisions to Protect the Privacy Interest of Participants .................................................14
22.
Economic Burden to Participants ......................................................................................14
23.
Informed Consent..............................................................................................................14
24.
Setting................................................................................................................................17
25.
Resources Available...........................................................................................................17
26.
Multi-Site or Collaborative Research ................................................................................17
27.
References.........................................................................................................................18
28.
Protocol Checklist ..............................................................................................................19

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1. Study Summary
Project Title
Revealing protective immunity to influenza using 
systems immunology (PRISM)
Project Design
Open-label
Primary Objective
To evaluate the immunogenicity of the live attenuated 
influenza vaccine (LAIV) 
Secondary Objectives
To analyse the effect of the LAIV on eliciting influenza-
specific immune responses
To assess the safety profile of LAIV
Exploratory Objectives
 
 
 
 
 
 
 
 
Research 
Intervention(s)/Interactions
Single dose live attenuated influenza vaccine (LAIV)
Study Population
Healthy and immunocompetent adults aged 18 to 49 
years
Sample Size
50 participants
Study Duration for 
individual participants
1 month
Study Specific 
Abbreviations/ Definitions 
AR 
Adverse Reaction
BU
Boston University
CI
Chief Investigator

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CEIRR Centers of Excellence for Influenza Research 
and Response (CEIRR)
GCP
Good Clinical Practice
GMC
Geometric Mean Concentration(s)
GMT
Geometric Mean Titer(s)
HA
Hemagglutinin
HAI
Hemagglutination Inhibition titer
ICF
Informed Consent Form
ICH
International Conference on Harmonization
IMP
Investigational Medicinal Product
LAIV
Live Attenuated Influenza Vaccine
LAR
Legally Appointed Representative
NEIDL National Emerging Infectious Diseases 
Laboratories
PBMC Peripheral blood mononuclear cells
PI
Principal Investigator
PIL
Participant/ Patient Information Leaflet
REC
Research Ethics Committee
SAR
Serious Adverse Reaction
SOP
Standard Operating Procedure
TCR
T cell receptor
TIV
Trivalent inactivated influenza vaccine
Funding Source (if any)
Boston University funds
2. Objectives
Primary Objective:
Evaluate the immunogenicity of the live attenuated influenza vaccine (LAIV) 
Secondary Objectives:
1. Analyze the effect of LAIV on eliciting influenza-specific immune responses.
2. Assess the safety profile of LAIV 
Exploratory Objectives:
 
 

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3. Background
The influenza virus is notorious for its continuous mutation and potential to cause pandemics. 
This essentially creates a moving target for vaccine development, posing a significant challenge 
for global health. Current vaccines offer a certain degree of protection but are not fully 
effective due to the virus's ever-changing nature. In response to this, a live attenuated influenza 
vaccine (LAIV) was developed with the objective of providing a higher degree of protection. This 
type of vaccine has demonstrated remarkable effectiveness in children, with protection rates as 
high as 85%, significantly surpassing the protection provided by inactivated flu vaccines. This 
made LAIV a preferred choice for administration to young children.
However, when it comes to adults (individuals over 18 years of age), the scenario is markedly 
different. Recent studies have indicated a significant decline in LAIV's effectiveness in adults 
compared to children. Various clinical trials have reported that LAIV exhibits approximately 85% 
efficacy in children under the age of 18, which dramatically decreases to around 40%-60% in 
adults (18-49 years). This suggests that adults do not respond as well to LAIV as children do, 
despite the vaccine being highly potent in younger populations. In adults, the LAIV-induced 
immunity appears to be short-lived, often lasting for only one influenza season. This is startling, 
especially considering that in children, LAIV has shown to provide long-lasting protection even 
against mismatched strains. Understanding the factors behind this discrepancy is a critical need 
if we aspire to improve the protective efficacy of influenza vaccines across all age brackets. 
Unraveling this mystery could open the doors to the development of a superior flu vaccine, one 
that offers robust protection across all age groups.
To find the solution to this enigma, it's essential to study why adults don't respond as efficiently 
to LAIV as children do. This forms the foundation of our research proposal: to understand the 
potential factors influencing the varied response to LAIV in adults. 
 
 
 
 
 
To attain a comprehensive understanding, we will utilize a systems immunology approach and 
incorporate 'omics' technologies along with artificial intelligence (AI). This blend of cutting-edge 

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technologies will facilitate exploring a broad spectrum of aspects within the immune response 
and build a more complete picture of the complex interactions within the immune system.
 
 
 
 
 
 
 
 
 
 
The comprehensive insights from this study will enhance our understanding of how LAIV 
induces immunity. This will significantly contribute to the development of an improved, 
universally effective flu vaccine that could provide robust protection across all age groups, 
ultimately reducing the global burden of influenza.
4. Study Endpoints
Primary Endpoint:
• Quantification of antibody titers using hemagglutination inhibition (HAI) assays at day 30 
Secondary Endpoints:
Mean geometric fold rise in HAI titers at Day 30
Frequency of serious adverse events until Day 30 after vaccination
Exploratory Endpoints:

 
 
 
 
 
 
 
 

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
 
 
 
 
 
 
 
 
 
 
 
 
5. Study Intervention/Investigational Agent 
5.1 Description
Live attenuated influenza vaccine
The FDA-approved live attenuated seasonal influenza vaccine (LAIV) (FluMist®, AstraZeneca) is 
licensed in the US for people 2-49 years of age. The 2024-25 seasonal influenza vaccine will be a 
trivalent vaccine which will contain three distinct strains3: 
-
A/Victoria/4897/2022 (H1N1)pdm09-like virus
-
A/Thailand/8/2022 (H3N2)-like virus
-
B/Austria/1359417/2021 (B/Victoria lineage)-like virus.
The approved seasonal LAIV at the time of study enrollment will be obtained from the 
manufacturer. 
5.2 Drug Handling
LAIV will be stored at the Emory Investigational Drug Service (IDS) per the manufacturer’s 
instructions. It will be prepared by an IDS pharmacist on site at the Hope Clinic satellite IDS. 
Logs of receipt, temperature, maintenance, and disposal will be maintained in the study file. 
LAIV will be administered by a study nurse or provider at the Hope Clinic as a single 0.2mL dose 
given as 0.1mL spray in each nostril.
5.3 Accountability Procedures for Study Products

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The IDS pharmacist will maintain accurate drug accountability logs which will be kept at the IDS 
pharmacy until the completion of the study. Upon completion of the study, a final drug 
accountability will be done. Following the completion of the drug accountability, the original 
copies of the logs will be maintained. When the vaccine is administered to a participant, the 
date, time, and location of administration (intranasal) will be recorded in the participant’s study 
source documentation records.
6. Procedures Involved
For a schedule of procedures, see Appendix A.
6.1 Screening, Consenting, Vaccination Visit (D0) 
6.1.1 Potential participants interested in the study will respond to study ads. Recruiters from 
the Hope Clinic will then contact them for a telephone screening, during which the research 
study will be explained in lay terms and eligibility criteria will be reviewed. If all eligibility 
criteria are met and the participant remains interested, an in-person screening appointment 
will be scheduled. Prior participants in other studies conducted at the Hope Clinic, and who had 
indicated their willingness to participate in other studies may also be contacted for a telephone 
screening visit. 
6.1.2 At the in-person appointment, study staff will review the informed consent form with the 
participant and will answer all questions related to the study. Once the participant signs the 
informed consent, they will be assigned a unique study participation number. The following 
procedures will be performed:
-
Recording of demographic information and review of medical history including recent 
influenza infection, current medication use, and vaccination history (previous receipt of 
influenza vaccines).
-
Vital signs (all participants) and targeted physical exam as indicated based on review of 
participant health status.
-
A urine pregnancy test will be performed if the participant is of child-bearing potential.
-
Blood sample collection for baseline assays (60-70 mL)
-
Nasal samples (nasopharyngeal swabs, nasosorption from nares) collection for baseline 
assays
The following actions will be performed for vaccination:
-
Review of inclusion and exclusion criteria to confirm eligibility. 
-
Participants will receive the CDC influenza vaccine information sheet and review it prior 
to vaccination.
-
Participants will then receive LAIV via the intranasal route, administered by a clinical 
research nurse or provider. 
-
Participants will be observed for a minimum of 15 minutes for any immediate 
hypersensitivity reactions.

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The visit will last approximately 60 minutes.
6.2 Follow-up Visits (D2, D28)
All participants will return for follow-up visits following vaccination. During these visits, study 
personnel will:
-
Review the participant’s current health status.
-
Note any changes in health history since the screening visit, including current 
medication use and vaccination history.
-
Collect blood samples for immunologic assays (60-70 mL)
-
Collect nasal samples (nasopharyngeal swabs, nasosorption from nares) 
The visit will last approximately 30 minutes.
Total blood volume for all visits will be approximately 210 mL. 
7. Statistical Analysis Plan
This is an exploratory, non-placebo controlled analysis of immune responses obtained
from blood and nasal samples. This will provide us with descriptive data to analyze immune 
responses.
7.1 Statistical methods
The statistics will be descriptive, reported in the form of percentages, frequencies, geometric 
mean titres and geometric mean fold rises with 95% confidence intervals. For geometric means 
and fold rises, data will be logged, and confidence intervals calculated on this log scale, prior to 
transforming back onto the original scale for reporting and interpretation. Confidence intervals 
for proportions will be calculated using the binomial exact method.
7.2 Sample size
A sample size of 50 participants will be recruited. We have estimated, using published data4, 
that a sample size of 40 individuals will be enough to be adequately powered to find differences 
in functionality of T cells after vaccination at the 98% power to detect a mean of paired 
differences of 0.1 (estimated standard deviation of paired differences of 0.1, significance level 
of 0.05 using a two-sided paired t-test). Therefore, we will analyze 50 individuals to allow for up 
to 20% drop-out rate, and to adjust for interindividual variability and any skewness in the data 
distribution. The following analyses will be performed on all participants in the per-protocol 
(PP) cohorts.
7.3 Analysis of outcome measures
Samples will be processed and stored at the Hope Clinic Processing Laboratory prior to being 
shipped to the laboratory of Prof. Adriana Tomic (Boston University, MA, USA) for analysis.

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7.3.1 Analysis of HAI titers and analytes in serum
Frozen plasma will be transferred to Boston University for HAI titer determination and for O-
link/proteomics technology. The HAI assay will be performed on sera from day 0 and day 28 
after vaccination. Briefly, serum samples will be diluted 2-fold with PBS in duplicate 96-well V-
bottom plates and virus will be added for control and serially diluted from concentration 
corresponding to 8 HA units to 0.03 HA units. Plates will be incubated for 15min at RT before 
50uL of 0.5% chicken red blood cell solution will be added and for additional 1h before reading 
HAI activity. The HAI titre of a given sample is defined as the highest dilution of serum that 
prevents hemagglutination. A titre of five will be assigned to all samples in which the first 
dilution (1:10) was negative. 
Cytokines in serum samples before and after vaccination will be measured by a O-Link 
technology (Target 96 and/or Explore384 panels, O-Link, Boston, MA, US) according to 
manufacturer’s recommendations. Each sample will be measured in duplicate. Plates will be 
read using a Luminex LabMap200 instrument with a lower bound of 100 or 50 beads per 
sample per cytokine. For each well, we will consider the median fluorescence intensity (MFI) of 
all beads measured for a given cytokine and averaged the MFI of the two replicates. Values will 
be normalized to a control sample ran in each of the plates.
7.3.2 Analysis of adaptive immune responses 
Isolated and frozen peripheral blood mononuclear cells (PBMCs) will be transferred to Boston 
University for analysis of immune cells subsets using spectral and/or mass cytometry. PBMCs 
from samples obtained on day 0 and days 2-3 and 28 after vaccination, will be thawed and 
rested overnight. Next day 106 PBMCs/well will be stimulated overnight (12-16 hours) with the 
influenza peptide pool in 96-well V-bottom plates. Influenza peptide pool contains 483 peptides 
(20mers with 11aa overlap, Sigma Aldrich) spanning the entire influenza proteome and 24 
peptides with HLA-A*0201-specificity (9-10mers, Sigma Aldrich) generated against the influenza 
strain A/California/07/2009. Samples will then be stained with antibodies for analysis on the 
Cytek Aurora spectral cytometer. After acquisition, data will be normalised, and further data 
analysis will be performed using FlowJo v10 software.
8. Data and/or Specimen Banking
Particiants will be asked for permission for the principal investigator to keep any remaining
(residual) specimens derived from venous blood collection for possible use in future research 
studies, such as examining additional immunological assessments or testing for antibodies 
against other viruses or bacteria. Future use samples/specimens will not be sold or used 
directly for production of any commercial product. These samples/specimens are protocol-
required; thus, participants must agree to future use of these samples/specimens as a condition 
of their study participation.
All samples/specimens will be processed at the Hope Clinic and shipped regulary to Prof. 
Tomic’s lab at Boston University. The de-identified (all personal identifying information of the 

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participant will be removed) samples/specimens will be labeled and stored in freezers at -80°C 
or in liquid nitrogen tanks.
In keeping with NIH policy on scientific data sharing, immunologic assay results will be made 
publicly available through public database deposition and peer-reviewed publication. 
Participants will be fully de-identified (i.e., disseminated data will not contain direct identifiable 
information). Demographic data (e.g., age, race and/or ethnicity, sex/gender) associated with 
participants will be kept strictly separate from all experimental results. This practice has 
become standard to protect participant privacy.
9. Sharing of Results with Participants
Immunologic assay results will not be reported to participants as these are intended for 
research purposes only and therefore cannot be reported to patients per Clinical Laboratory 
Improvement Amendment (CLIA) regulations. 
Incidental findings 
Incidental findings such as pregnancy test results or physical exam findings identified during 
study conduct will be disclosed and explained to the participant by the study investigator, who 
will provide a referral to the appropriate clinical specialist and information on how to obtain 
health insurance to secure treatment if needed. Participants will be directed to follow up with 
primary care providers. 
10. Study Timelines
Individuals will participate in this study for a total of 1 month; the maximum time between V1 
and V3 will be 35 days. Recruitment of all participants will require 8 months. The primary 
analysis should be concluded within 48 months of start date. The study will be active for up to 6 
years to complete secondary and exploratory analyses.
11. Inclusion and Exclusion Criteria
Inclusion Criteria
1. Able to understand and give informed consent
2. Age 18-49 years
3. Participants of child bearing potential must agree to use effective birth control for the 
duration of the study. A negative urine pregnancy test must be documented prior to 
vaccination. 
Exclusion Criteria 
1. History of allergy or serious adverse reaction, including Guillain-Barré syndrome, to a 
vaccine or vaccine products

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2. History of a medical condition resulting in impaired immunity such as active solid 
tumors, leukemia, lymphoma, chemotherapy or radiation therapy, autoimmune 
conditions, or splenic dysfunction. Persons with previous skin cancers or cured non-
lymphatic tumors are not excluded from the study.
3. History of asthma, cochlear implant, or active cerebrospinal fluid leak
4. Use of immune modifying drugs including: systemic steroids for more than 1 week (such 
as prednisone > 20mg/day), chronic administration (more than 14 days total) of 
immunosuppressive or immunomodulatory drugs in the prior 3 months
5. History of HIV, Hepatitis B or Hepatitis C infection
6. Chronic clinically significant medical problems that could be considered active or 
unstable (i.e diagnosed within the past 3 months or requiring a change in medication 
within the past 3 months). This is including (but not limited to):
a. Insulin dependent diabetes
b. Severe heart disease (including arrhythmias)
c.
Severe lung disease
d. Severe liver disease
e. Severe kidney disease
f.
Severe hypertension: defined as life-threatening consequences (e.g., malignant 
hypertension, transient or permanent neurologic deficit). 
g. Congenital genetic syndromes (e.g., trisomy 21)
7. BMI > 35
8. Pregnancy or breast feeding, or plans to become pregnant in the next month
9. History of influenza infection or vaccination within the current or previous influenza 
season
10. Receipt of blood products or immune globulin product within the prior 3 months 
11. History of excessive alcohol consumption, drug use, psychiatric conditions, social 
conditions or occupational conditions that in the opinion of the investigator would 
preclude compliance with the trial
12. Receipt of any live vaccines 30 days before, or plans to receive any live vaccines 30 days 
after vaccination
13. Receipt of any inactivated vaccines 14 days before, or plans to receive any inactivated 
vaccines 14 days after vaccination
14. Receipt of any non-registered or other investigational product in 30 days before, or 
plans to receive any other investigational product 30 days after vaccination
Temporary Exclusion Criteria
1. Fever (temperature ≥38.0°C) or coryzal symptoms within 72 hours prior to vaccination
2. Receipt of antipyretics within 6 hours prior to vaccination
Participants meeting time-limited exclusion criteria may be re-screened at investigator 
discretion.
12. Population

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No vulnerable populations will be enrolled. Specifically, pregnant persons, children, prisoners, 
and cognitively impaired persons will not be enrolled. Non-English speakers will not be 
excluded. 
13. Local Number of Participants
We anticipate needing to screen up to 70 participants locally to identify 50 participants to 
complete the research procedures. 
14. Recruitment Methods
14.1 Patients will be recruited following IRB approval.
14.2 Participants will be recruited from the general population of metro Atlanta with the 
methods detailed below. 
14.3 Participants may be identified and recruited from past subjects who agreed to be 
contacted for future studies or by self-referral from IRB approved advertisements from

postings of IRB-approved flyers in and around the Emory University campuses as well as 
on electronic notification boards ; posting approved flyers on Emory and partner 
institution shuttles (e.g., Georgia Tech); 

use of various social media platforms such as Facebook, Twitter, Instagram, and other 
mobile apps in compliance with Emory policy; Study staff will use the official Emory 
University Facebook account and Instagram Emory Get Involved account, where IRB 
approved social media ads will be posted. The potential volunteers fill in their contact 
information in the “lead document form” provided by Facebook by default. The form 
collects the potential participant’s basic contact information such as name, best contact 
phone number and email address etc. Facebook collects the leads and provides it to the 
recruitment staff, who save the data in a password protected database on the Emory 
Hope Clinic’s shared drive. See social media plan for additional detail.

listservs (such as CDC, Emory University, Emory Vaccine Center, and Vaccine Dinner 
Club), and clinical trial recruitment websites such as Research Match.org and 
ClinicalConnection; listing of clinical trials on the Hope Clinic website 
(hopeclinic.emory.edu) and Emory clinical trials database (clinicaltrials.emory.edu); 
contacting past participants from the HIPAA-compliant clinical trials database at the 
Hope Clinic who have agreed to be contacted for future studies; presentations by Hope 
Clinic faculty at various University and community venues; and volunteer word-of-mouth 
(direct referrals).

Potential subjects may also be recruited from a list of potentially eligible volunteers identified 
through a general screening online survey (created with the Emory-approved Qualtrics platform) 
hosted on the Hope Clinic website. The survey captures contact, demographic, and basic health-
related questions (i.e. flu vaccine status). Participants who meet preliminary study eligibility 
criteria for this study will be contacted via their indicated preferred method of contact,  provided 
more information about this study, and administered a study-specific phone screen by a Hope 
Clinic recruiter.

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Study recruiters/coordinators will contact potential volunteers via email or phone call once 
identified and tell them about the study and see if they are interested. If the potential subject is 
interested, the recruiter will obtain an oral consent and prescreen them for the study using an 
IRB-approved screening checklist. Qualified subjects will be scheduled to come into the clinic 
and be fully consented and proceed with screening/enrollment.
15. Withdrawal of Participants
Participants may voluntarily withdraw their consent from all future study activities including 
follow up at any time without penalty or loss of benefits to which they are otherwise entitled. 
Participants may be terminated from the study prior to study completion for reasons that might 
include, but are not limited to, those listed below. The investigator will inform the participant 
that all data acquired prior to termination will be included in the study analysis unless 
participant withdraws consent.
15.1 Participant no longer meets eligibility criteria. 
15.2 The participant is considered by the PI to be “lost to follow-up” (i.e., no further followup is 
possible because attempts to reestablish contact with the subject have failed).
15.3 The participant chooses not to allow future use of samples for research purposes.
15.4 The participant dies.
15.5 As deemed necessary by the PI or designee for noncompliance of any nature.
15.6 The participant becomes pregnant.
15.7 If the study is prematurely terminated by the sponsor or the investigator for any reason, 
the investigator will promptly inform the study participantsand assure appropriate follow-up, as 
necessary. The investigator will provide a detailed written explanation of the termination to the 
IRB.
Participants with early termination status (before Day 28) are replaced as needed to preserve 
adequate sample size for the primary endpoint analysis.
16. Risk to Participants
16.1 Risks of Investigational Product
Seasonal influenza vaccine
The potential harms of receiving the approved seasonal influenza vaccine include, but are not 
limited to: nasal congestion, runny nose, wheezing, headache, cough, fever, or muscle aches. 
These reactions occur in 10-20% of adults who receive influenza vaccine. Serious adverse 
reactions including anaphylaxis and Guillain-Barré syndrome are possible, but rare. Potential 
participants with a history of severe allergic reaction to any component of the vaccine or 
Guillain-Barré syndrome after previous influenza vaccination will not be enrolled. For further 
details, see the attached package insert.
16.2 Risks of Study Procedures

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Blood draws
The risks of blood sample collection include a transient feeling of discomfort and may result in a 
vasvogal reaction. This risk is controlled by having the participant lie down prior to collection, if 
needed. A bruise might form at the site of the blood draw, and this can be avoided by 
maintaining pressure to this site following the blood draw. The sites of blood draw are potential 
sites of infection, but this risk is made very unlikely by the use of sterile technique.
Nasal sampling
The risks of nasal sample collection are minimal including discomfort, eye watering, or mild 
nosebleed. The amount of discomfort and risk of nose bleeds will be minimized by using 
experienced staff or ensuring that new staff are properly trained and observed. If a nosebleed 
occurs, clinical staff will assist the participant with applying pressure or other treatments as 
needed.
16.3 Risk of Concomitant Medications, Prophylactic Medications and Rescue Medications
While we do not expect to use any additional medication, in case of anaphylactic or 
hypersensitivity reactions, we have readily available epinephrine (1:1000) and 
diphenhydramine injections. The use of epinephrine injection may cause side effects such as 
high blood pressure, arrhythmia, lightheadedness, nervousness, restlessness, tremor, shortness 
of breath, and diaphoresis; however, the frequency of these side effects is not determined. 
Diphenhydramine injection may also be necessary to treat potential allergic reactions, and its 
use may cause low blood pressure, arrhythmia, confusion, dizziness, sedation, restlessness, 
diarrhea, nausea, and urinary retention, but the frequency of these side effects is also 
unknown.
When facing a medical emergency, the clinic staff will follow the institutional SOP by calling 911 
first (Hope Clinic). If needed, the participant will be transferred to Emory University Hospital or 
Emory Decatur Hospital Emergency Department for further care.
Participants are permitted to use acetaminophen or other symptomatic treatment if they 
experience a moderate to severe local or systemic side effect after vaccine administration. 
17. Potential Benefits to Participants
Participants will receive the FDA-approved seasonal influenza vaccine, which may protect 
against influenza viruses. The United States Advisory Committee on Immunization Practices 
(ACIP) recommends the influenza vaccine for individuals aged 6 months and above, as it is 
known to be effective in preventing influenza virus infection.
18. Compensation to Participants
As compensation for expenses/travel and time, participants will receive $125 for the 
screening/vaccination visit and $75 for each follow-up visit that involves a blood draw. 
Compensation is provided in the form of a gift debit/credit card (ClinCard). If a participant 

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completes all visits, total compensation will be $275. In the event gift debit/credit cards 
(ClinCard) are unavailable, gift card reimbursement may be used instead. 
19. Data Management and Confidentiality
19.1 Steps taken to secure data
All faculty and staff at the Hope Clinic receive HIPAA, human participants, and EHSO training as 
part of their onboarding and continuing training. Each participant will be assigned a unique 
study participant identification number (PTID) and these numbers rather than names will be 
used to collect and store participant information, including omics data. 
Investigators and study personnel will keep accurate records to ensure that the conduct of the 
study is fully documented. Clinical data from this study, including participant birthdate and 
demographics, will be associated with the PTID, maintained on a HIPAA compliant clinical 
management database (Clinical Conductor) and a HIPAA compliant RedCap database and/or 
password protected Excel file, respectively at Hope Clinic accessible to investigators and study 
personnel only. Hard copy clinical data forms, for example source or protocol-specific Hope 
Clinic CRFs, associated with the PTID will be stored  at Hope Clinic in a locked filed cabinet and 
accessible to investigators and clinical staff only. A file linking the participant PII (i.e., their name 
and contact information) to their PTID will be maintained at the Hope Clinic in a separate 
locked file cabinet and HIPAA compliant clinical management database accessible to 
investigators and clinical staff only. Study personnel will only send documents containing 
personal PII via fax or encrypted email in accordance with HIPAA regulations (e.g., to 
send/receive medical records request to/from primary care provider).
19.2 Quality Control 
The Principal Investigator (or designee) will keep accurate records to ensure that the conduct of 
the study is fully documented. The investigator will ensure that all Hope Clinic CRFs and 
participant study files are legible and complete for every participant. The Principal Investigator 
(or designee), through the use of an internal Quality Management Plan, appropriate site quality 
control, and quality assurance monitoring staff, will be responsible for the regular review of the 
conduct of the study for verifying adherence to the protocol, and for confirming the 
completeness,  consistency, and accuracy of all documented data and accuracy of source 
documentation verification. All charts will be 100% Quality Controlled. The first five volunteers 
enrolled will receive a 100% Quality Assurance review. The reports of the internal site monitor 
will be submitted to the Principal Investigator (or designee). The RedCap data entry system will 
include checks for data that are outside feasible limits (e.g., dates that are in the future) or 
skipped answers.
19.3 Data and specimen handling
Blood tubes will be labeled at the Hope Clinic with a unique identifier and will be transported to 
the lab at the Hope Clinic in EHSO-approved transport containers. All de-identified samples will 
be stored at the Hope Clinic by laboratory staff using only the study number, PTID, date of visit, 

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and visit number. Data from immunological assays will be linked to PTID, maintained by Dr. 
Tomic’s laboratory at Boston University, and accessible to investigators and laboratory staff. 
Laboratory data and demographic data may be linked by PTID for statistical analysis by 
investigators or collaborators (e.g., to control for age); however, PTID will not be published in 
order to protect participant privacy.
Specimens and demographic data linked by PTID will be stored indefinitely, but all personal 
identifiable information (PII) and PII/PTID links will be destroyed once the laboratory analysis 
associated with this protocol is complete and the last manuscript associated with this protocol 
has been published.  
Study investigators and personnel will maintain the highest degree of confidentiality for the 
clinical and research information obtained from the participants. Medical and research records 
will be maintained in the strictest confidence. However, as a part of the quality assurance and 
legal responsibilities of a clinical study, investigators will permit authorized representatives of 
regulatory authorities to examine (and when required by applicable law, to copy) clinical records 
for the purpose of quality assurance reviews and evaluations of study safety and progress. Unless 
required by laws that permit copying of records, only the PTID associated with documents or with 
other participant data may be copied (and all personally identifying information will be removed). 
Authorized representatives described above are bound to maintain the strict confidentiality of 
medical and research information that is linked to identify individuals.
20. Plans to Monitor the Data to Ensure Safety of Participants and Data Integrity
☐ No more than minimal risk 
Participants in this study will not receive investigational vaccine. Minimal risk is involved.
Select one of the following (do not delete this table; review the guidance document 
for definitions):
☐ Medium Complexity
☐ High Complexity Category A
☒ High Complexity Category B
If choosing this category for a study under an IND or IDE because you believe the 
study intervention does not significantly impact morbidity or mortality, please 
provide your rationale:

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DSMP Requirement
How this Requirement is 
Met 
Frequency
Responsible 
Party(ies)
Real-time review of 
participant data 
during initial data 
collection.
100% QC review by CRC/CRN 
and peer review within 3 
business days. QM will 
review first 5 participants in 
real time.
Expectation is that 
this happens every 
time you obtain 
information.
CRC/CRNs 
QM 
Manager/Team
Site Monitoring at 
pre-determined 
intervals: The 
Principal Investigator 
has a responsibility to 
ensure that the study 
is following all aspects 
of the protocol. 
There should be a standard 
operating procedure to 
review data (whether a 
sample or 100%) at pre-
determined intervals to 
ensure that there is 
adequate documentation of 
critical elements such as 
eligibility criteria. Monitoring 
is required at the following 
timepoints (but may be done 
more frequently):

study initiation  

at least every six 
months while 
participants are 
receiving intervention 
and 

annually while 
participants are in 
follow-up
At a minimum, a 
review is required 
annually when no one 
has been enrolled or 
the study is in long 
term follow up. 
Additional risk-based 
interim monitoring 
may be required at 
least once every 12-24 
weeks based on the 
site activity, to include 
the possibility of 
remote monitoring. A 
longer frequency 
could be acceptable 
with justification 
about risk to 
participants.
Delegate a 
responsible 
party for each 
requirement 
below. Self-
assessment is 
acceptable*.
Self-
assessment: a 
process for 
self-
assessment of 
protocol 
compliance 
and data 
integrity which 
can be part of 
an overall 
DSMP. See 
CTAC’s self-
assessment 
tool on their 
webpage. 
100% review of 
regulatory files
Site QM will conduct 100% 
review of reg files at the 
beginning and at close-out 
visit at a minimum. 
Reviewed at a 
minimum of first and 
close-out visits
QM 
Manager/Team
Regulatory 
Team
100% review of 
consent forms
CRC/CRNs will perform peer 
review in real time for 100% 
of ICFs.
Real time
CRC/CRNs
QM 
Manager/Team

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QM will conduct 100% 
review of ICFs.
Review of credentials, 
training records, the 
delegation of 
responsibility logs (if 
applicable)
QM and Regulatory Team 
will conduct 100% review of 
credentials/training 
records/DoA files quarterly 
at a minimum.
Quarterly
QM 
Manager/Team
Regulatory 
Team
Comparison of case 
report forms (CRF) to 
source 
documentation for 
accuracy and 
completion
QM will conduct 100% 
review for first 5 participants 
in real time and on a 
monthly basis throughout 
the study.
Monthly
QM 
Manager/Team
Review of 
documentation of all 
adverse events
SAEs will be reviewed by PI 
and designee and peer 
reviewed by CRC/CRNs and 
verified by QM team and 
evaluated by the ISM and 
Emory IRB. 
As events occur
CRC/CRNs
QM 
Manager/Team
Monitoring of critical 
data points (eligibility, 
study endpoints, etc.)
QM will conduct 100% 
review for first 5 participants 
in real time and on a 
monthly basis throughout 
the study.
Monthly
QM 
Manager/Team
Laboratory review of 
processing and 
storage of specimens
Peer review of sample log in 
done in real time and 
answering queries regularly 
Reviewed at first and 
close-out visits and at 
least biannually
Lab Manager 
or designee
Assessment of 
laboratory specimens 
stored locally
Peer review of sample log in 
done in real time and 
answering queries regularly- 
shipment done within 2 
weeks
Real time
Lab Manager 
or designee
Test article 
accountability review
Day to day and monthly per 
IDS pharmacist
Reviewed at first and 
close-out visits and at 
least biannually
Research 
Pharmacist
Accountability logs, 
dispensing records, 
Monthly per IDS pharmacist
At least biannually
Research 
Pharmacist

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and other participant 
records 
For FDA regulated 
studies, the following 
requirements apply:
Timing, frequency, 
and intensity of 
monitoring
Monitoring methods 
(may include 
centralized, on-site, 
and self-assessment)
Monitoring visits will 
include, but are not limited 
to, review of regulatory files, 
accountability records, 
electronic case report forms 
(eCRFs), ICFs, medical and 
laboratory reports, site 
study intervention storage 
records, training records, 
and protocol and GCP 
compliance. Site monitors 
will have access to each 
participating site, study staff 
and all study documentation 
according to the Hope Clinic 
CQMP. Study monitors will 
meet with all participating 
site PIs to discuss any 
problems and outstanding 
issues and will document 
site visit findings and 
discussion.
Monitoring visits are 
expected to occur 
monthly or bimonthly. 
Details of clinical site 
monitoring are 
documented in a 
clinical monitoring 
plan (CMP). The CMP 
describes in detail 
who will conduct the 
monitoring, at what 
frequency monitoring 
will be done, at what 
level of detail 
monitoring will be 
performed, and the 
distribution of 
monitoring reports.
Monitoring for 
this study will 
be performed 
by the QM 
team.
*For international studies, you are required to engage a CRO that is working in the site country 
and/or to consult with Emory’s legal counsel regarding compliance with the country’s clinical 
research regulations.
20.1 Study Oversight
The Principal Investigator and the research team (co-Investigators, research nurses, study 
coordinators, and data managers) are responsible for identifying adverse events. Adverse 
events will be reviewed regularly by the research team.
20.2 Adverse Events
This section defines the types of adverse events that may occur, and outlines the procedures 
for appropriate adverse event collecting, grading, recording, and reporting.
Information in this section complies with 21CFR 312; ICH Guideline E2A: Clinical Safety Data 
Management: Definitions and Standards for Expedited Reporting and Good Clinical Practice; 

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and applies the standards set forth in the National Cancer Institute (NCI), Common Terminology 
Criteria for Adverse Events Version 5.0 [Published: November 27, 2017; 
http://evs.nci.nih.gov/ftp1/CTCAE/About.html]. These criteria have been reviewed by the study 
investigators and have been determined to be appropriate for this study population.
20.2.1 Adverse Events Definition
An adverse event (also referred to as an adverse experience) can be any unfavorable and 
unintended sign, symptom, or disease temporally associated with the use of the procedure, 
without any judgment about causality.
After vaccination, the following adverse events in the indicated intervals may be reported to 
Vaccine Adverse Event Reporting System (VAERS).
-
Anaphylaxis or anaphylactic shock (7 days)
-
Vasovagal syncope (7 days)
-
Any acute complication or sequelae (including death) of above events (interval - not 
applicable)
-
Events described in manufacturer’s package insert as contraindications to additional 
doses of vaccine: hypersensitivity, including severe allergic reactions after previous dose 
of influenza vaccine
20.2.3 Suspected Adverse Reaction (SAR)
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that the drug or procedure caused the adverse event. Suspected adverse reaction implies a 
lesser degree of certainty about causality than adverse reaction, which means any adverse 
event caused by a drug.
SARs after vaccine administration may include:
-
Local reactions: congestion, runny nose, wheezing
-
Systemic reactions: headache, fever, nausea, dizziness.
SARs after phlebotomy may include:
-
Local reactions: pain at the site of venipuncture, bruising at the site of venipuncture, 
infection at the site of venipuncture
-
Systemic reactions: lightheadedness or fainting
20.2.4 Serious Adverse Event (SAE) or Serious Suspected Adverse Reaction
An adverse event or suspected adverse reaction is considered ‘‘serious’’ if, in the view of the 
investigator, 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
-
A congenital anomaly/birth defect

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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 participant and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Serious adverse events will be reported and 
recorded for the entire duration of the study.
An adverse event or suspected adverse reaction is considered ‘‘life-threatening’’ if, in the view 
of the investigator, its occurrence places the patient or participant at immediate risk of death. It 
does not include an adverse event or suspected adverse reaction that, had it occurred in a more 
severe form, might have caused death.
Any serious adverse event (for duration of study) will be recorded and reported within 24 hours 
to ISM.
20.2.5 Unexpected Adverse Event or Unexpected Suspected Adverse Reaction
An adverse event or suspected adverse reaction is considered ‘‘unexpected’’ if it is not listed in 
the Summary of Product Characteristics or is not listed at the specificity or severity that has 
been observed; or, if the Summary of Product Characteristics is not required or available, is not 
consistent with the risk information described in the general investigational plan or elsewhere 
in the current application, as amended.
20.2.6 Independent Safety Monitoring
The ISM is a physician with relevant expertise in clinical studies whose primary responsibility 
will be to provide independent safety monitoring in a timely fashion and to provide 
recommendations regarding the safe continuation of this study.
The ISM, Dr. David Rimland, will evaluate safety data generated from study participants against 
the known safety profile of the study product or study procedure to assess for possible changes 
to the overall risk of the study. In addition to the reporting timelines noted in section 20.3.3, 
the ISM will review safety data annually and communicate with the Principal Investigator as 
needed. The study has provisions for a back-up ISM to ensure that independent safety 
monitoring happens at all times during the study.
20.2.7 Collecting and Recording Adverse Events and Pregnancy
Adverse events may be identified during this study through any of these methods:
-
Examination of the participant during study visits.
-
Questioning the participant during study visits.
-
Receiving a safety contact from the participant at any time during the study
Note: participants will be asked to call the site if they develop any of the following:
-
Any adverse event that limits self-care activities of daily living (e.g. bathing, dressing and 
undressing, feeding self, using the toilet, taking medications, and not bed ridden) even if 
he/she decides not to seek medical care

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Serious adverse events will be recorded if they occur at any time during the study. 
A complete recording of safety events in the CRF will include event term; date(s) of onset and 
resolution/stabilization; assessment of severity; relationship to procedures/intervention(s); 
expectedness; determination of whether the AE qualifies as serious or non-serious; treatment 
required; action taken with study  articipation; and outcome. AEs qualifying as serious also 
require a narrative of the event. Updates in safety events will be recorded as additional 
information becomes available.
Information on pregnancies will be collected from the time a participant signs the consent until 
the participant completes study participation. If a participant becomes pregnant after study 
entry, the investigator will discuss with the participant and/or the treating provider the known 
possible risks to the fetus. Participants becoming pregnant after study entry will be withdrawn 
from the study and followed until the end of the pregnancy for safety. A pregnancy resulting in 
congenital anomaly/birth defect will be considered a SAE. Any premature termination of the 
pregnancy will also be reported and assessed as an SAE as needed.
20.3 Grading and Attribution of Adverse Events
20.3.1 Grading Criteria
Adverse events will be graded according to the criteria set forth in the National Cancer Institute’s 
Common Terminology Criteria for Adverse Events Version 5.0 [November 27, 2017; 
http://evs.nci.nih.gov/ftp1/CTCAE/About.html] This document (referred to herein as the NCI-
CTCAE manual) provides a common language to describe levels of severity, to analyze and 
interpret data, and to articulate the clinical significance of all adverse events. All adverse events 
whether or not listed in the NCI-CTCAE will be graded on a scale from 1 to 5 according to the 
following standards in the NCI-CTCAE manual (A semicolon indicates ‘or’ within the description 
of the grade):
-
Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.
-
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL*.
-
Grade 3 Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL**.
-
Grade 4 Life-threatening consequences; urgent intervention indicated.
-
Grade 5 Death related to AE.
*Instrumental Activities of Daily Living (ADL) refer to preparing meals, shopping for groceries or 
clothes, using the telephone, managing money, etc.
**Self-care Activities of Daily Living (ADL) refer to bathing, dressing and undressing, feeding 
self, using the toilet, taking medications, and not bedridden.

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Not all Grades are appropriate for all AEs; therefore, some AEs are listed with fewer than five 
options for Grade selection.
Anaphylaxis is a disorder characterized by an acute inflammatory reaction resulting from the 
release of histamine and histamine-like substances from mast cells, causing a hypersensitivity 
immune response. Clinically, it presents with breathing difficulty, dizziness, hypotension, 
cyanosis and loss of consciousness and may lead to death. Severity grading of anaphylaxis as 
per the NCI-CTCAE manual is as follows:
-
Grade 1= not applicable
-
Grade 2= not applicable
-
Grade 3= Symptomatic bronchospasm, with or without urticaria; parenteral intervention 
indicated; allergy-related edema/angioedema; hypotension
-
Grade 4= Life-threatening consequences; urgent intervention indicated
-
Grade 5= Death
20.3.2 Definition of Attribution
The site investigator will initially determine the relationship of an adverse event. The 
relationship of an AE to study participation will be determined as RELATED or UNRELATED.
20.3.3 Reporting Timelines
Reporting Adverse Events to the Independent Safety Monitor
Any unexpected adverse event grade 3 or higher related to phlebotomy up to 7 days after the 
procedure will be reported within 7 days to ISM.
Any SAE will be reported to the ISM by email within 24 hours of becoming aware of the event. 
The ISM may request further information if necessary and possibly request changes to the 
protocol or consent form as a consequence of the adverse event.
Notifying Institutional Review Board
The Principal Investigator will ensure the timely dissemination of SAE information, including 
SAEs requiring expedited review by the ISM and to the IRB in accordance with IRB regulations 
and guidelines. Serious adverse events that are unanticipated, related to study participation, 
and involving risk to participant or others will be reported to the IRB within 10 business days of 
event occurrence or of the PI becoming aware of the event per IRB guidelines.
21. Provisions to Protect the Privacy Interest of Participants
A participant’s privacy and confidentiality will be respected throughout the study. Each 
participant will be assigned a unique patient identification number (PTID) and these numbers 
rather than names will be used to collect and store participant information and samples. A file 
linking the participant identity, i.e., name, to their unique study participant ID (PTID) is 
maintained at the Hope Clinic in a separate locked file cabinet and on a HIPAA compliant clinical 
management database. Screening, consenting, and study visits will take place in private clinic
rooms.

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Any publications from this study will not use information that will identify participants by name 
or PTID. A description of this trial will be available on http://www.ClinicalTrials.gov, as required 
by US Law. This web site will not include information that can identify participants . At most, this 
web site will include a summary of the results. Site personnel will only transmit documents 
containing personal identifiable information (PII) using encrypted email or fax in accordance with 
HIPAA regulations (e.g., to send/receive safety lab data and medical records to/from primary care 
provider).
22. Economic Burden to Participants
There is no cost to participants for the research tests, procedures, or study product while taking 
part in this study. Procedures and treatment for clinical care may be billed to the participant, 
participant’s insurance or third party. Participants may be compensated for their participation in 
this study. Compensation will be in accordance with the local IRB policies and procedures, and 
participant to IRB approval.
If it is determined by the principal investigator that an injury occurred to a participant as a direct 
result of the tests, procedures or treatments that are done for this study, then referrals to 
appropriate health care facilities will be provided to the participant. Study personnel will try to 
reduce, control, and treat any complications from this study. Immediate medical treatment may 
be provided by the participating site. No financial compensation will be provided to the 
participant for any injury suffered due to participation in this study.
23. Informed Consent 
23.1 Statement of Compliance
This study was designed to ensure the protection of participants according to the ethical 
principles of the Declaration of Helsinki and amendments concerning medical research in human 
participants. This clinical study will be conducted using current good clinical practice and 
according to the criteria specified in this study protocol. Before study initiation, the protocol and 
the informed consent documents will be reviewed and approved by the IRB, as well as any other 
appropriate health authorities. Any amendments to the protocol or to the consent materials will 
also be approved by the appropriate bodies listed above prior to implementation.
23.2 Informed Consent Process
The informed consent form will provide information about the study to a prospective participant 
to allow for an informed decision about participation in the study. Prospective participants must 
be given ample opportunity to review the informed consent and inquire about the results of the 
study. The consent form will be provided electronically to the prospective participant during the 
first screening phone call for their review. A copy of the informed consent form will again be 
provided to a participant for review prior to any study procedure during the in person screening 
visit. The Principal Investigator or an approved designee will discuss the consent with the 
prospective participant and answer questions. Study staff will read through the consent form 
with potential participants and answer any questions. Participants will be allowed sufficient time 

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to consider participation in the study, after having the nature and risks of the trial explained to 
them and have the opportunity to discuss the trial with their family, friends. The prospective 
participant will be told that being in the study is voluntary and that he or she may withdraw from 
the study at any time, for any reason. The consenting process will take place in private exam 
rooms at the Hope Clinic. We anticipate that the consent process will take about 30-45 minutes.
All participants must read, sign, and date a consent form before undergoing any study 
procedures. Consent materials will be provided in the English language, however, shortforms 
and a qualified interpreter are available and IRB approval will be requested for use in 
consenting non-English speaking participants. A copy of the signed consent form will be given 
to the participant. The informed consent form will be revised and receive IRB approval 
whenever important new safety information is available, whenever the protocol is amended, 
and/or whenever any new information becomes available that may affect participation in the 
study. 
24. Setting
Potential participants will be recruited and screened from the general population of metro 
Atlanta. Participants will be enrolled at the Hope Clinic, Decatur, Georgia.
25. Resources Available
The Hope Clinic has a database of more than 5000 previous volunteers who can be considered 
for screening for the study. The Hope Clinic also has a website and the ability to reach out to 
potential participants through advertising around the Emory University campus.
25.1 Facilities
The Hope Clinic is a community-based vaccine research clinic and is the clinical arm of the 
Emory Vaccine Center. 
25.2 Participant Support
Referrals to appropriate medical or psychological health care facilities will be provided by the 
investigators to the participant as needed due to the anticipated consequences of human 
research. Study personnel will try to reduce, control, and treat any complications from this 
study. Immediate medical treatment may be provided by the relevant site (Hope Clinic).
25.3 Study Personnel Training
All faculty and staff at the Hope Clinic receive HIPAA, human participants , and EHSO (e.g., 
bloodborne pathogens) training as part of their onboarding and continuing training. In addition, 
all study personnel will complete ongoing approved protocol review and provide 
documentation of this training to study quality management personnel.
26. Multi-Site or Collaborative Research 
All human subjects research activity for this protocol will occur at the Hope Clinic. Deidentified 
samples will be transported to Dr. Tomic’s lab as described in section 19.

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27. References
1.
Tomic A, Tomic I, Rosenberg-Hasson Y, Dekker CL, Maecker HT, Davis MM. SIMON, an 
Automated Machine Learning System, Reveals Immune Signatures of Influenza Vaccine 
Responses. J Immunol. 2019;203(3):749-759.
2.
Santos A, Colaco AR, Nielsen AB, et al. A knowledge graph to interpret clinical 
proteomics data. Nat Biotechnol. 2022;40(5):692-702.
3.
U.S Food and Drug Administration. Use of Trivalent Influenza Vaccines for the 2024-
2025 U.S. Influenza Season. https://www.fda.gov/vaccines-blood-biologics/lot-
release/use-trivalent-influenza-vaccines-2024-2025-us-influenza-season. Accessed 7 
March 2024.
4.
Sridhar S, Begom S, Bermingham A, et al. Cellular immune correlates of protection 
against symptomatic pandemic influenza. Nat Med. 2013;19(10):1305-1312.
28. Protocol Checklist
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 

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Appendix A. Schedule of Procedures
 
D0
D2
(2-3)
D28
(26-32)
V1
V2
V3
Informed consent
x
Demographics, medical 
history
x
Interim medical history
x
x
Medications
x
x
x
Targeted physical exam
x
(x)
(x)
Vital signs
x
(x)
(x)
Pregnancy test 
(if applicable)
x
Vaccination
x
Blood draw
x
x
x
Nasal sampling
x
x
x
Conducting a visit outside window is allowed at investigator discretion
Parentheses indicate a given procedure will be conducted if relevant for the visit