An Open Label Study of IgG Fc Glycan Composition in Human Immunity
Phase: EARLY_PHASE1
Conditions: Healthy
Sponsor: Rockefeller University

 Study Application (Version 1.38)
1.0
General Information
*Please enter the full title of your study::
An open label study of IgG Fc glycan composition in human immunity
*Please enter the study short title:
Fc glycan composition in human immunity
* This field allows you to enter an abbreviated version of the Study Title to quickly identify this study.
Is this Study using Subject Management?
Yes
No
2.0
Add departments
2.1 List departments associated with this study:
Is
Primary? Department Name
RUH - Laboratory of Molecular Genetics and Immunology (Ravetch)
RUH - Rockefeller University Hospital (RUH)
3.0
Assign key study personnel(KSP) access to the study
3.1 * Please add a Principal Investigator for the study:
Name
Role
Training Record
Wang, Taia, MD, PhD
Principal Investigator
 View Training Record
3.2 If applicable, please select the Research Staff personnel:
A) Additional Investigators
Name
Role
Training Record
Caskey, Marina F, M.D.
Clinical- Co-Investigator
 View Training Record
Ravetch, Jeffrey, MD PhD
Clinical- Co-Investigator
 View Training Record
B) Research Support Staff
Name
Role
Training Record
NCT01967238
Protocol Date: 10/26/2022 

3.0
Assign key study personnel(KSP) access to the study
Colagreco, Joseph P, DNP, NP-BC
Study Coordinator
 View Training Record
3.3 *Please add a Study Contact:
Name
Role
Training Record
Colagreco, Joseph P, DNP, NP-BC
Study Contact
 View Training Record
Wang, Taia, MD, PhD
Study Contact
 View Training Record
The Study Contact(s) will receive all important system notifications along with the Principal Investigator. (e.g. The project
contact(s) are typically either the Study Coordinator or the Principal Investigator themselves).
4.0
Rockefeller University Conflict of Interest
4.1   Investigator Financial Conflict of Interest All KSP must complete an annual certification of their Significant
Financial Interest (“SFI”) disclosures in the University’s online Research Administration System at
https://RAS.rockefeller.edu.  Disclosures also must be updated in connection with new human subjects
research protocols (“Research Certification”), and within 30 days of discovering or acquiring a new SFI.  To
avoid delays in the IRB review process, when prompted by an email from rascoi@rockefeller.edu requesting
an updated Research Certification, KSP should click on the Research Certification link contained in that email
notification, or go to https://RAS.rockefeller.edu, to (a) review and update his or her SFI disclosures or
certify that he/she has no updates, as appropriate, and (b) indicate whether any of his/her SFI disclosures
are reasonably related to the design, conduct, or reporting of the research protocol. If a KSP discloses a SFI
that might constitute a conflict of interest with respect to the proposed protocol, he or she must e-mail a
copy of the Lay Summary of the draft protocol to Teresa Solomon, Esq. (solomot@rockefeller.edu).  Doing so
will facilitate addressing COI issues in step with the development of the study protocol.  Non-compliance or
tardiness in making or updating COI disclosures will result in a delay in IRB review.      Institutional Conflict
of Interest:
 
As early as possible the PI (or a designee) preparing a clinical research protocol must review a list of
entities in which The Rockefeller University has an Institutional Financial Interest at
https://icoi.rockefeller.edu/account/login.php.  If the proposed study involves any entity on that list, the PI
(or designee) must notify Teresa Solomon, staff to the FCOI Committee, by e-mail solomot@rockefeller.edu
and Sarah Schlesinger, Chair of the IRB, by email: schless@rockefeller.edu, provide the name(s) of the
entities and a copy of the Lay Summary. Doing so will facilitate addressing institutional COI issues in step
with the development of the study protocol. Failure to take steps to review and address potential
institutional conflicts of interest will delay the IRB review process.  
5.0
External Personnel
5.1   List external personnel who will be working on the study:
Name
Institution
Telephone
E-mail
Role
Maurice Policar,
MD 
Elmhurst hospital
 
(718) 334-
4952 
JONESM@nychhc.org
Consultant
Shiv Pillai, MD,
M.P.H. 
Massachusetts
General Hospital 
617-726-5619 
pillai@helix.mgh.harvard.edu Collaborator
Joseph R.
Masci, MD  
Elmhurst hospital
 
(718) 334-
3446 
JONESM@nychhc.org
Consultant
John Stone,
MD, PhD 
Massachhusetts
General Hospital 
617-643-5385 
jhstone@partners.org
Collaborator
6.0
Delegation of Authority

6.1   Enter authorized activities for all Rockefeller University personnel named on the study. 
Activity Codes:
1.   Informed consent **
11.  Participant recruitment
21.  Skin biopsy *
2.   Inclusion / exclusion criteria
12.  Perform assays 
22.  Conduct sleep study
3.   Medical/medication history *
13.  Specimen / sample analysis
23.  Diet design and preparation
4.   Perform Physical Exam *
4a. Write / Sign LIP orders *    
14.  Lumbar puncture *
24.  Nutritional assessment and
counseling
5.   Skin assessments and photos
15.  Femoral line placement *
25.  Addition of PABA to food 
6.   Study drug dispensing *
16.  Central line placement * 
26.  Data analysis
7.   Study drug administration *
17.  Insulin clamp procedure *
27.  Data review
8.   Study drug reconciliation
18.  Leukapheresis *
28.  Data management 
9.   Study drug compliance
19.  Sigmoidoscopy * 
29.  Maintain regulatory documents / files
10. Administer study questionnaire(s)
20.  Fat biopsy *
30.  Complete CRF's
Add up to three additional authorized activities specific to this study (do NOT add activities
that have previously designated codes):
31:
32:
33:
 Activity Codes Continued:
34.  Behavioral Testing
35.  Bod Pod
36.  Bone Marrow Aspiration *
37.  Neuropsychological Testing *
38.  Conduct Focus Group 
39.  Conduct Smell Study
40.  Genetic Counseling *
41.  Apply EEG Electrodes **
42.  Olfactometer Test
43.  Study Participant Teaching
44.  Resting Energy Expenditure 
45.  Source Document Review & Correction 
46.  Medical Photography
47.  See 4a 
48.  Adverse Event Assessment
49.  Clinical Trial Registration 
50.  Study Support Drug Dispensary
51.  Internal Monitoring 
52.  Randomization 
Enter delegation of authority for Rockefeller University Key Study Personnel:
NOTE:
*     Indicates procedures requiring the individual complete specific credentialing BEFORE the activity
may be added to their delegated activities.
**  Indicates procedures requiring the individual complete specific training BEFORE the activity may be
added to their delegated activities.
Name
Title
Authorized Activities
Start Date
End Date

Wang, Taia,
MD, PhD
PI
1, 11, 12,13, 26, 27, 28, 29,
30
01/09/2013
11/03/2022
Buckley,
Noreen, M.S.,
APRN-BC
Clinician
1,2, 3, 4, 7, 11, 28, 29, 30
01/09/2013
05/01/2015
Hurley,
Arlene, MA,
ANP-BC,
CCRC
Clinician
1, 2, 3, 4a, 7, 10, 11, 28, 29,
30, 45, 48
01/09/2013
10/13/2021
Caskey,
Marina F,
M.D.
Co-I
1, 2, 4a, 11, 12,13,26,27,28,
29, 30
01/10/2013
11/03/2022
Schlesinger,
Sarah J, M.D.
Co-I
1, 2, 4, 11, 12,13,26,27,28,
29, 30
01/10/2013
07/06/2017
Ravetch,
Jeffrey, MD
PhD
Co-I
11, 12,13,26,27,28, 29, 30
01/10/2013
11/03/2022
Pack, Maggi,
Ph. D
Co-I
11, 12,13,26,27,28, 29, 30
01/10/2013
10/21/2016
Rosenberg,
Brad R, MD,
PhD
Co-I
11, 12,13,26,27,28, 29, 30
01/10/2013
01/29/2014
Rice, Charles,
Ph.D.
Co-I
11, 12,13,26,27,28, 29, 30
01/10/2013
01/29/2014
Hadrigan,
Sonya, Nurse
Practitioner
Clinician
1,2, 3, 4, 7, 11, 28, 29, 30
01/13/2015
05/01/2016
Breton,
Gaelle, PhD
Co-I
12, 26
02/17/2015
10/21/2016
Nussenzweig,
Michel
Claudio,
M.D., Ph.D.
Co-I
26, 27
02/17/2015
10/21/2016
Levin,
Rebeka, BS
RN
1,2,3,7,10,11,28,29,30,31
03/02/2016
07/06/2017
Butler,
Allison, MSN,
FNP-BC
NP
1,2,3,4a,7,10,11,28,29,30,48
05/17/2016
11/21/2019
Millard,
Katrina G,
ANP
NP
1,2,3,4a,7,10,11,28,29,30,48
07/11/2016
11/21/2019
Eylers, Ellen,
MPH, MSN,
RN, CCRC
Coordinator
1,2,10, 11,27,28, 29,30,31
10/21/2016
11/01/2017

Enter delegation of authority for additional Rockefeller University Key Study
Personnel:
Name
Title
Authorized Activities
Start Date
End Date
Brassil,
Donna,
MA, RN,
CCRC
Facilitator
1,2,10,11,27,28,29,48
11/09/2017
10/13/2021
Colagreco,
Joseph P,
DNP, NP-
BC
Study
Coordinator
1,2,3,4a,7,10,11,28,29,30,45,48
11/21/2019
11/03/2022
Enter the authorized activities for External Personnel:
Name
Title
Authorized
Activities
Start Date
End Date
No results found
7.0
Study Description
7.1  
Study Classification
Full Review
7.2  
* Submission Request Category
Note: For each submission, please designate the level of review, or “Submission Request Category” you are
requesting. When completing this field, please indicate the level of review you are requesting for the
specific submission you are working on.
For example, if you are submitting an Expedited Amendment request to change the Key Study Personnel on
your existing Full Board study, you should select “Expedited Review” in both the Amendment Submission
Form and Study Application. The IRB will confirm an Expedited review of the Amendment submission is
appropriate, and the overall study will remain classified as a full Board review. Please see the help bubble
for guidance.
To submit a request for a Not Human Subjects research determination, please exit this form and
select the “Not Human Subjects Research Determination” form under Create a New Study.
Exempt from Review 
Exempt with Limited Review 
Expedited Review 
Full Review 
7.3   * Lay Summary
Please provide a summary of your study in lay language that is easily understood by a non-scientist. The
summary should be no more than half a page (500 words or less) and should contain a clear statement of
the rational for the study.
Please provide a summary of your study in lay language.  The summary should be no more
than a half page (500 words or less) and should contain a clear statement of the rationale for
the study. 

Antibodies are principle mediators of immunity against infections and they can also give rise to
autoimmune and inflammatory diseases.  Two functional domains make up an IgG antibody – the Fab
domain binds to a specific target, while the Fc domain can interact with receptor molecules to activate
a pro- or anti- inflammatory state.   The Fc domain of IgGs contains a glycan that is variable in
composition and its specific sugar components are an important determinant of the biologic activity of
IgGs in both protective and pathologic immune responses.  New disease treatments could be developed
through purposeful manipulation of IgG Fc glycans, but there is currently little known about how Fc
glycan composition is regulated.  We plan to study this by evaluating whether vaccination or infection
can cause changes in Fc glycan composition and, if so, whether signaling from helper T cells, age of the
patient, and/or route of vaccine administration are determinants of specific modifications that are
triggered by vaccination.   Next, we will study effects that specific components within the Fc glycan
have on immunity against the common human pathogens Streptococcus pneumoniae and influenza
viruses using in vitro and in vivo models of infection.
 
7.4  
* Public Health Impact Statement
Provide a brief plain language statement (100 words or less) of the value of the research
proposed and its potential impact on population health. Additional instructions located in Help.
 
In order to produce better more effective vaccines, it is important to understand the particulars of why
individuals have an effective or ineffective immune response to vaccination. We are going to examine
specific aspects of the antibody (IgG Fc glycan) made by healthy volunteers who receive different
vaccines or who have a viral infection to understand the nature of an effective (or less effective) vaccine
response. The results of this research could be used to develop adjuvants to increase/ improve vaccine
response.
8.0
Clinical Trial Registration
8.1  
Clinical Trial Registration
The types of studies listed below must be registered at Clinical Trials website before
enrolling the first participant in order to be in compliance with federal regulations and
preserve the opportunity to publish the study in journals that adhere to the ICMJE
guidelines. Please check the answer that best applies.
Study involves testing of FDA regulated drugs or biologics (See HELP) 
Study is funded by the NIH, and meets the definition of a “clinical trial” (see HELP) 
Study meets the ICMJE definition of a “clinical trial” (See HELP) 
Additional funding agency or journal requires clinical trial registration 
None of the above 
If you selected 1, 2, 3, or 4 you must register your trial with ClinicalTrials.gov through the
Rockefeller University institutional account. Please contact the Clinical Research Support Office
x7408 for assistance.
9.0
Study Overview/Summary
9.1   * Who initiated this study?

Please specify one:
Principal Investigator Initiated 
Industry Initiated 
Other 
9.2   *Are other institutions involved in the study?
No 
Yes 
9.3   * Is this a multi-site trial using a single IRB (sIRB) review arrangement? Please see help bubble for
definition.
  Yes  
  No
9.4  
* Who (What) is to be studied?
Human Subjects - including coded samples and/or data with links to Identifiers
Deidentified Samples - unable to be linked to identifiers by receiver
Data Only - unable to be linked to identifiers
Identifiable samples or data for exemptions (per 104 (s)(4))
9.5   *Study Type:
Interventional 
Observational 
9.6   The initial date of IRB approval/determination was:
02/07/2013
9.7   * What is the expected duration of the study?
10 years
9.8   * Are any of the following agents to be used in the study?
Check all that apply:

FDA Approved Drug
FDA Approved Drug for Off-Label Purpose (This might require an IND)
Investigational New Drug
Biologic Agents
Nutritional Supplements
Placebo
Vaccines
No Agents
FDA Exemption to use Study Drug
9.9   * Are investigational devices to be used in the study?
  Yes  
  No
9.15   Special Research Procedures
Does the study propose to directly involve participants in the following special research
procedures?
Recombinant DNA
Gene Therapy
Fetal Tissue
Embryonic Stem Cells
Induced Pluripotent Stem Cells
CRISPR-Cas9
If any item is checked, please see Help for details.
9.16   * Radioactive Isotopes Involved
Will participants be exposed to any radiation other than routine x-rays solely for clinical care
purposes? 
  Yes  
  No
 
10.0
Interventional
10.1   *Interventional, please specify:
Open Label 
Single Blind 
Double Blind 
Other 
11.0
Study Phase:
11.1   Study Phase:

Select where applicable
Phase 0 
Phase I 
Phase I/II 
Phase II 
Phase III 
Phase IA 
Phase IB 
Phase IIA 
Phase IIB 
Phase IB/IIA 
Phase IIB/IIIA 
Phase IIIA 
Phase IIIB 
N/A 
12.0
Objectives and Rationale
12.1   * Overview
Briefly state the purpose of this study. Give enough background and rationale to provide
both scientists and lay members of the IRB and ACCTS with the basis for exposing human
participants to the risks involved.
Antibodies represent an important link between the adaptive and innate immune systems. IgG
antibodies are bifunctional molecules comprised of a Fab domain, which determines binding specificity
through the variable region, and an Fc domain, which interacts with a variety of receptors on immune
cells to confer effector function to IgG molecules.  These effector functions include positive regulatory
mechanisms such as the activation of antibody-dependent cellular cytotoxicity (ADCC), phagocytosis,
and pro-inflammatory cytokine production, as well as negative regulatory functions, such as inhibition
of inflammatory immune responses.   Effector functions are conferred via the Fc domain through
specific amino acid residues in the Fc and the precise glycan composition of an N-linked, complex,
biantennary glycan that regulates interactions with members of the IgG Fc receptor (FcR) family and
the DC-SIGN family of molecules (1, 2).
The Fc glycan is a powerful regulator of antibody effector function and its specific composition can
determine whether an antibody has pro- or anti-inflammatory activity in vivo (3-6).  For example, the
presence of terminal sialic acid on the Fc glycan converts IgGs to anti-inflammatory molecules in a
variable region-independent manner. This is exemplified in studies demonstrating that the therapeutic,
anti-inflammatory activity of intravenous immunoglobulin (IVIG) is conferred solely through the
fraction of IVIG containing Fc glycans terminating in sialic acid, which have been shown to interact with
SIGN molecules expressed by innate immune cells (4, 7).   Similarly, the presence or absence of a
branching fucose moiety modulates the interaction of the IgG Fc with activating Fc receptors to
enhance or inhibit IgG mediated cellular cytotoxicity (6, 8, 9).
Though the precise saccharide composition of Fc glycans is known to be a significant determinant of
the biologic activity of IgGs, little is known about how the composition is regulated or about the
biological consequences of specific modifications.  Interestingly, it has been observed in mice and in
humans that exposure to immunogens can result in various modifications of the IgG glycan (4, 10).
 We plan to study this phenomenon using seven different FDA-approved vaccines; by characterizing Fc
glycans in pre- and post- immunization sera, we will define the type of antigen(s) that can elicit
changes in Fc glycan composition in humans.  We will also study whether healthy adults who have been
previously infected with a flavivirus or alphavirus (dengue, zika or chikungunya) generate distinct Fc
glycoforms after vaccination compared with healthy adults who have not had known infection with
dengue, zika or chikungunya virus infection; for this study we will use the seasonal inactivated
influenza vaccine  because influenza reagents for analysis of the TIV-elicited IgGs are abundant and
readily available.
We will also use existing serum samples from controlled influenza virus infection studies performed at
the NIAID in order to study how specific Fc glycoforms on influenza-specific IgGs may change during
infection and to compare Fc glycan modulations that may occur during infection with those elicited by
vaccination.   In addition, we will use existing serum samples from a study performed at Emory
University.   These samples were drawn from patients with dengue virus infection, during acute
infection, following defervescence and 1-2 months post infection.  We will use these samples to study
how Fc glycoforms on dengue envelope protein-specific IgGs may change during infection and we will
compare any changes with those observed on IgGs from patients with influenza virus infection.

That antigen exposure can modify Fc glycan composition suggests a possible role for cognate B cell - T
cell interactions in the regulation of glycan composition.  Accordingly, a second phase of this study will
investigate whether T cell help is required for vaccine-elicited glycan modification.  We will study this
by comparing serum IgG Fc glycan profiles in volunteers who were vaccinated with either T cell
dependent (TD) or T cell independent (TI) vaccine antigens.  We will also evaluate whether the age of
the patient or route of vaccine administration are determinants of vaccine-elicited glycan modification. 
Finally, we plan to study how specific IgG glycan modifications regulate immunity against
Streptococcus pneumoniae and against influenza viruses in in vitro and in vivo models of infection.
12.4   * Engaging Stakeholders: Describe any plans to engage other stakeholders (Scientists, practitioners,
patients, advocacy groups, etc.) for hypothesis generation, or feasibility purposes.  
The Principal Investigator as well as other members of the Ravetch laboratory were involved in the
hypothesis generation and the feasibility purposes of this application.
12.5   * Hypothesis
Describe the research hypothesis in a single sentence.
The saccharide composition of human IgG Fc glycans determines effector function of pathogen-specific
IgGs during infection and may be distinct in people with prior symptomatic flavivirus or alphavirus
infection, can be modulated by exposure to specific types of vaccine antigens or modulated during viral
infection.
12.6   * Aim(s)
Indicate how you will address the hypothesis (e.g., to compare groups, to estimate a
parameter, to ascertain feasibility). Since the sample size determination is usually based on
the primary aim only, the primary aim should be sufficient to justify the study.
Aim 1:
To determine whether vaccination can elicit modifications in Fc glycan composition and, if so, whether
the T cell dependence of a vaccine antigen, age of the patient at vaccination or route of vaccine
exposure regulate observed modifications in the IgG Fc glycan.
 
Aim 2:
To determine how specific components of the IgG Fc glycan regulate immunity against influenza viruses
and against Streptococcus pneumoniae in in vitro and in vivo models of infection.
 
Aim 3:
To determine whether infection with influenza virus or dengue virus infection can elicit modifications in
Fc glycan composition and to compare any changes with those observed following vaccination.
 
Aim 4:
To determine whether people who develop clinically significant flavivirus or alphavirus (dengue, zika or
chikungunya)  infection produce distinct Fc glycans in response to vaccination.
 
Aim 5:
To determine the Fc glycosylation status and in vivo activity of IgG4 antibodies from patients with IgG4
diseases
12.7   * Primary Outcome(s)
Indicate which variable(s) will be assessed to judge the primary specific aim.  Give
measurement units, if applicable.
Determination of saccharide components of the IgG Fc glycan pre- (day 0) and post- (day 7
and day 21) vaccination with different vaccines and before, during and following influenza
virus infection:
 
- The degree of galactosylation, fucosylation and sialylation of pre- vs. post- vaccination Fcs
determined by lectin blot (Erythrina cristagalli, Aleuria Aurantia Lectin and Sambucus nigra lectins
specific for galactose, fucose and 2,6-sialic acid, respectively).
- Characterization of glycan composition by mass spec analysis.

Determination of the role of route of antigen exposure, age of the patient, or past flavivirus
or alphavirus infection in regulation of Fc glycan modifications.
- Using three influenza virus vaccines (two inactivated that are administered either intramuscularly or
intradermally, and one live that is administered intranasally) we will compare how the route of
administration affects modifications of the Fc glycan by western blot and mass spec analysis.
- By comparing vaccine responses in patients < 65 or ≥65 of years of age we will determine how age
regulates post-vaccination modifications of the Fc glycan.
12.8   * Secondary Outcome(s)
Indicate which additional variable(s) will be assessed to judge the secondary outcome(s).
Give measurement units, if applicable.
 
Characterization of effector function of pathogen-specific IgGs during infection as a function of Fc
glycan composition:
- The IgG subclass distribution will be determined using data resulting from the mass spec analysis
performed for the primary study outcome.
- In vitro analysis of antibody dependent cell cytotoxicity and antibody dependent cellular phagocytosis
mediatedby anti-influenza IgG with different Fc glycan profiles.
- In vitro analysis of cellular maturation and function using PBMCs from study participants.
- Analysis of gene expression using PBMCs from study participants.
- In vivo analysis of protection mediated by anti-influenza or anti-pneumococcal IgG with different Fc
glycan composition in murine influenza virus or pneumococcal models of infection.
12.9   * Methods and Procedures
Please provide a description of the laboratory and clinical analyses and procedures that will be
performed. Include the role of external collaborators and consultants when appropriate. Please
refer to Help text for Guidance.
Study Design:
The study population consists of healthy volunteers between the ages of 18 and 80.
 
215 volunteers who meet all the eligibility criteria will be enrolled in this study. 
 
The study is divided into 3 arms. The groups are defined as follows:
 
Arm I: Age 18-64 group: Groups of 10 study participants each (except for group 2 which includes 25
participants) < 65 years of age (< 50 years of age for Flumist vaccine and < 55 years of age for
meningococcal vaccines) will be vaccinated with one of seven FDA approved vaccines (85
participants total): Group 1) Fluzone intradermal influenza virus vaccine, Group 2) Fluzone
intramuscular influenza virus vaccine, Group 3) Pneumovax 23 (plain polysaccharide pneumococcal
vaccine), Group 4) Prevnar/PCV13 (pneumococcal conjugate vaccine), Group 5) MPSV4 (plain
polysaccharide meningococcal vaccine), Group 6) Menveo (meningococcal conjugate vaccine), Group
10) Flumist Quadrivalent (intranasal influenza live vaccine).
 
Arm II: Age 65-80 group: Groups of 10 study participants ≥65 years of age will be vaccinated with
one of three of the FDA approved vaccines (30 participants total): Group 7) Fluzone
intramuscular influenza virus vaccine, Group 8) Pneumovax 23, Group 9) Prevnar.   Meningococcal
vaccines, the intradermal influenza vaccine and intranasal Flumist will not be administered to
participants in Arm II.
 
Arm III: Healthy adults, age 18-80, with a specific medical history as described here and in
Section 12.11 (Inclusion Criteria): Groups of 25 study participants will be vaccinated with the
Fluzone intramuscular influenza virus vaccine (100 participants total). Group 11) Prior diagnosis of
dengue fever or dengue virus infection.  Group 12) Prior diagnosis of dengue hemorrhagic fever.   
Group 13) Prior diagnosis of chikungunya virus infection. Group 14) Prior diagnosis of zika virus
infection
 
The study will occur in four phases:
Phase 1: Volunteers will be recruited to receive influenza vaccines (Groups 1, 2, 7, 10).  Recruitment
for Groups 1 and 7 will occur simultaneously and volunteers will be enrolled sequentially - enrollment
into Group 1 will be given priority over Group 2 because the intradermal vaccine preparation for the
2012-13 influenza season will expire earlier than the intramuscular preparation (April 2013 vs. June
2013). Volunteers will be recruited to receive the Flumist influenza vaccine (Group 10) beginning fall of
2013.
 

Phase 2: Volunteers will be recruited to receive one of the pneumococcal vaccines (Groups 3, 4, 8, 9)
- these subjects will be recruited simultaneously and will be randomized to receive either the
Pneumovax or Prevnar vaccines.
 
Phase 3: Volunteers will be recruited to receive one of the meningococcal vaccines (Groups 5 and 6) -
these subjects will be recruited simultaneously and will be randomized to receive either the MPSV4 or
Menveo vaccines.
 
Phase 4: Volunteers will be recruited for Arm III of the study to receive the Fluzone intramuscular
vaccine (Groups 11-14)
Study participants will not be blinded.  During the analysis phase, samples will be coded so that the
precise vaccine administered within each phase is unknown.
 
Study visits will be scheduled as follows for groups 1-10: screening, day 0 (within 4 weeks of screen),
day 7 safety visit, and weeks 3, 5, 7, 9, and 12. On Day 3-4, a telephone call will be made to check on
subject's medical status.
Groups 11-14 will be scheduled as follows: day 0 (within 4 weeks of screen), day 7 safety visit, and
week 3.  We will not collect samples at weeks 5,7,9 or 12 for Groups 11-14 because our existing data
on intramuscular Fluzone immunization from Group 2 demonstrate that the major Fc glycan
modifications occur during the first 3 weeks following vaccination.  
 
We do not anticipate any safety issues related to this protocol as all vaccines to be used
have been FDA approved and all study participants are healthy adults.
 
Protocol Timeline
See Study Design groups 1-10 in other study documents
See Study Design groups 11-14 in other study documents
 
Subjects in Groups 1 and 2 (Fluzone ID < 65 years of age and Fluzone IM < 65 years of age) will be
asked to return to the clinic for an additional study visit between 6 and 12 months from their Day of
Vaccination (Day 0). This visit will include vital signs, any updates to their medical/vaccination history,
as well as a blood draw of 23.5 ml for sera and PBMCs. The rationale to include this additional
timepoint is that our data from subjects who received the 2012-13 Fluzone vaccines show modulations
in Fc glycan composition on antigen-specific IgGs post vaccination; the Fc glycans change over time
following vaccination, but are not at baseline composition by the 12 week timepoint (the latest
timepoint) in our study.  Inclusion of the 6-12 month timepoint in the Fluzone study groups will enable
better characterization of the kinetics of Fc glycan changes, which is important since the modifications
are likely to augment IgG effector functions.  We will collect a detailed history of any vaccinations or
illnesses occurring since the last study visit in order to incorporate the information into our analysis. 
Sera collected at this late timepoint will enable analysis of Fc glyan composition and PBMCs will enable
analysis of vaccine-specific B and T cell functioning.
 
Screening Procedure and Study Visits
Potential participants will first undergo pre-screening by telephone to assess medical history and
qualification for the study.  Potential volunteers will have the opportunity to discuss the study and
ask questions of the study recruiter at this time. Those who are eligible and interested in participation
will attend a screening visit at the Rockefeller Hospital Outpatient Clinic.
 
Screening Visit: Study personnel will answer any questions about the study. Written informed consent
will be obtained prior to conducting any study procedures. To ensure informed consent, the principal
investigator or designee will discuss the following processes and explanations individually with each
volunteer:
1. Pre HIV-test counseling;
2. Risk-reduction counseling including safe-sex and pregnancy avoidance counseling;
3. That a sexually active volunteer should use a reliable form of contraception throughout the
study.
4. For Arm III, study personnel will request authorization from the participant to obtain their
medical records as possible and/or speak to the treating provider from the time of virus
infection.  Participants will be asked to sign the HIPPA Compliant Authorization for Release of
Medical Information.   
If the volunteer consents to participate, site personnel will:
Perform complete medical history (including concomitant medication);
Perform a general physical examination including height, weight, vital signs (pulse, respiratory
rate, blood pressure and temperature), examination of skin, respiratory, cardiovascular and
abdominal systems, and an assessment of cervical and axillary lymph nodes;
Safety labs will be drawn (WBC with differential, RBC, hemoglobin/hematocrit, platelets, Na, K,
Cl, CO2, bun/creatinine, glucose, total and direct bilirubins, alkaline phosphatase, AST, ALT
and urinalysis), as well as serologies -Hep BsAg and HCV for all Groups, for Groups 11-14
additional serologies will be performed for dengue and chikungunya viruses to ensure eligibility
and vaccine safety.  Rapid point of care (POC) saliva test will be performed to test for
HIV.
Perform a pregnancy test for all female volunteers;

 
Day 0, Vaccination Visit: Prior to vaccination, site personnel will:
Answer any questions about the study;
Review interim medical history (including concomitant medications);
Review safety laboratory data;
Review the informed consent form administered at screening visit with volunteer;
Perform a physical examination including vital signs (pulse, respiratory rate, blood pressure and
temperature), examination of skin, respiratory, cardiovascular and abdominal systems, and an
assessment of cervical and axillary lymph nodes;as well as an assessment of axillary lymph
nodes and any further examination indicated by history or observation;
Risk-reduction counseling including safe-sex and pregnancy avoidance counseling;
Safety labs will also be drawn prior to vaccination.
Research bloods (81mL) will be drawn.  
Perform a point of care pregnancy test for all female volunteers and obtain results prior to
vaccination;
Perform baseline assessment of the site of injection and evaluate and record any systemic
symptoms;
Each participant will then receive a vaccination with one of the seven FDA approved vaccines.
Participants will be monitored in the clinic for any vaccination reactions. Vital signs will be
performed pre and post vaccination.
Presence or absence of local and/or systemic reactogenicity events, as well as any other event
that occurs, will be recorded post vaccination.
 
Day 7:
Safety labs will be drawn.
Research bloods (81mL) will be drawn.
A targeted physical examination including vital signs (pulse, respiratory rate, blood pressure
and temperature), as well as an assessment of axillary lymph nodes and any further
examination indicated by history or observation will be performed.
Perform a point of care pregnancy test for all female volunteers.
 
Weeks 3, 5, 7, 9, 12:
Vital signs (pulse, respiratory rate, blood pressure and temperature) will be taken.
Research bloods (20-170mL) will be drawn.
Perform a point of care pregnancy test for all female volunteers.
Groups 11-14 will not have bleeds done at week 5,7,9,12 or thereafter.
 
During follow up visits at day 7 and weeks 3, 5, 7, 9 and 12, study participants will receive pregnancy
testing prior to sample collection because pregnancy is known to alter Fc glycan composition and would
thus significantly confound study results. Volunteers with positive pregnancy tests will be discontinued
from further participation in the study.
 
Withdrawal from the study (Early Termination)
Volunteers may be withdrawn from the study permanently for the following reasons:
1. Volunteers may withdraw from the study at any time if they wish to do so, for any reason.
2. Following an adverse event at the discretion of the investigator (or designee).
Blood Collection
Venous blood will be collected at study visits, usually from the antecubital fossa.  Up to 20-170mL will
be collected at study visits.  At no time will the total volume of blood collected exceed 550 mL over an
8-week period.  The total blood volume over the 12 week study period is 615mL. The volume of blood
was increased to 615mL to conduct exploratory studies that are indicated by preliminary data from the
influenza virus vaccine cohort.   We have seen that there are modifications in IgG Fc glycan content
induced by vaccination and that glycan composition may correlate with the avidity of vaccine-elicited
IgGs.   As a follow-up to these observations, we will evaluate how specific glycan modifications may
correlate with activation and function of a variety of different peripheral blood cell types, some of which
are found in extremely low frequency, such as DCs and CD4 follicular T helper cells. These studies will
require PBMCs from an additional 80mL of blood at each of three time points in the study timeline:
baseline, day 7 and week 3. This is now reflected in the total blood volume of 615mL. All specimens
will be handled and processed in the GLP Processing Lab of the Laboratory of Cellular Physiology and
Immunology. Only a code number will identify the samples.  Frozen PBMCs, plasma and serum will be
stored at RU.
 
Reimbursement
Volunteers will be compensated $75 for their vaccine visit, $35 for the follow-up blood draw visits
except for the final visit, for which participants will be compensated $75.   Reimbursement will be
outlined in the informed consent form.
 
It is expected that volunteers for Arm III will be more likely to live outside of the immediate area, as
patients with prior flavivirus or alphavirus infection are relatively rare.  In consideration of anticipated

travel time for volunteers in Arm 3, participants will receive $25 for the screening visit, and
compensation will be a minimum of $100 for each visit.
 
Sample preparation and laboratory analysis
Leukocytes will be separated from plasma, red blood cells and platelets by Ficoll (GE) gradient
centrifugation. Plasma, serum and cells will be frozen for analysis at a later time. The serum will be
characterized for cytokines using luminex multiplex assays and ELISAs.   Serum will also be used to
extract IgGs for analysis by ELISA, western blot and by mass spec for specificity and Fc glycan
content.   Fc glycans will be analyzed following isolation of antigen-specific IgGs by affinity
chromatography.   Vaccine preparations or purified proteins/polysaccharides will be coupled to
sepharose beads as previously described for extraction of specific serum IgGs (11-14).   Fc glycans
from antigen-specific IgGs will be isolated by digestion with EndoS enzyme for subsequent mass spec
analysis of the Fc glycan (15).   Vaccine preparations for research use will be obtained from the RU
pharmacy, purified influenza virus antigens will be obtained from the Biodefense and Emerging
Infections Research Resources Repository, purified pneumococcal polysaccharides from ATCC. Serum
IgGs will also be used in in vitro and in vivo (murine) assays in the laboratory to assess the functional
consequence of Fc glycan modifications during infection with influenza viruses or with Streptococcus
pneumonia (16-18).   Mice humanized for FcgRs will be used for in vivo studies using human IgGs
(19).  RNA will be extracted from samples collected in PAXgene tubes for analysis related to specific
modifications of IgG Fc glycans occuring post-vaccination.
 
In addition to the above samples, we will study existing serum samples from a study performed at
NIAID in which healthy volunteers were infected with influenza virus in a controlled hospital setting.
 Samples will be obtained from an exiting collection from approximately 30 study participants from the
following time points: pre-infection, day 3 post infection, day 7 post infection, week 3 post infection
and week 5 post infection (for a total of 150 samples).  Subjects in the infection study performed at
NIAID consented to future use of samples for scientific investigation and samples will be de-identified
without any accompanying information containing patient identifiers.  Laboratory analysis of the serum
samples will follow the same protocol as described above for sera collected under the vaccination
protocol. Investigators from the NIAID will not be collaborating on this research; they will not be
receiving any data derived from this study, will not participate in data analysis, and will not co-author
any publications stemming from this study.
 
In addition to the above samples, we will study existing serum samples from a study performed
through Emory University in which patients with diagnosed dengue virus infection had blood drawn.
 Samples will be obtained from an existing collection from approximately 10 study participants from
the following time points: acute infection, post-defervesence, and 1-2 months post-infection.  Subjects
in this study consented to future use of samples for scientific investigation and samples will be de-
identified without any accompanying information containing patient identifiers.  Laboratory analysis
of the serum samples will follow the same protocol as described above for sera collected under the
vaccination protocol. Investigators from Emory will not be collaborating on this research; they will
not be receiving any data derived from this study, will not participate in data analysis, and will not co-
author any publications stemming from this study.
 
With the August 2018 amendment, de-identified research samples (serum) will be received from
collabrators from the Massachusetts Genral Hospital (Pillai and Stone) obtained from patients with
IgG4 related diseases. A total of approximately 20 research samples will be received in the Ravetch
laboratory.   There will be no attempt on the part of the Principal Investigator at the Rockefeller
University to link the identity of the participant to the research sample nor will the collaborators at
Massachusetts General Hospital provide the code to the identity of the participant sample.  The MGH
collaborators will receive the data derived from this study as it relates to their research samples as
needed.
 
 
 
 
 
12.10   * Data Analysis
Describe method(s) of data analysis. 
In order to find evidence that IgG Fc glycan composition changes from
pre- to post-vaccination, we will apply two-sided t-tests and wilcoxon

tests for paired samples with significance fixed at 5% when evaluating
change in abundance of specific saccharide units.   For each vaccine
antigen, we will be comparing pre- (day 0) to post- (day 21)
vaccination IgG Fc glycan composition in order to see which vaccines
elicit significant saccharide modifications.   We will apply the same
analysis to data obtained through study of samples taken prior to and
at day 21 post influenza virus infection.  For the analysis of the time
course experiment and comparison across different groups, we are
going to use Repeated Measures ANOVA, descriptive graphics and
possibly fitted curves that may bring information about changes in
time. Depending upon results in humans (Aims 1 and 2), in vivo
experiments will be carried out in mice. For this stage, our
Biostatistical Core will be consulted about the appropriate design and
analysis of the experiments.
 
12.11   * Explain the rationale for the choice of statistical measures and the number of participants
proposed for the study, including the power calculations when applicable.
Sample size evaluation was carried out to provide 80% power  and 5% of significance for a
two-tailed paired t-test to verify pre-post differences in the relative abundance of sugars. For
each one of the specific saccharides to be measured, we expect an effect size a 10% change in
relative abundance, with a standard deviation of 4.4% - this is based on data presented in
Selman et al. (2012). Selman et al. evaluated changes in IgG1 Fc saccharide abundances
(galactosylation, fucosylation and sialyation) following influenza vaccination of 10 Caucasian
adults. Based on their data, we selected the highest standard deviation, which occured in
abundance of sialyation.  Adjustments for error multiplicity were done by a Bonferroni-
Correction that reduced the individual significance levels to be 0.017 (0.05 significance divided
by 3 sugars evaluated).  Another adopted measure for taking into account the uncertainty
about the standard deviation was to inflate that estimate by multiplying it by 1.30. This
caused our standard deviation to increase to 5.72% from 4.4%.  After all described
procedures, using the function n.ttest in package samplesize in R, the initial evaluated sample
size resulted in n=7 per group.   It is important to emphasize that only samples from subjects
with a two-fold increase in vaccine-specific antibody titer will be further analyzed for IgG Fc
glycan saccharide composition. Thus, the evaluated sample size was increased to n=10 to
accommodate the possibility of having a 20% rate of vaccine non-responsiveness and also the
expected rate of volunteer drop-off (10%).
ARM III: We have preliminary data on the abundance of afucosylated glycans on anti-dengue
envelope protein IgG
from patients with acute dengue virus infection- the data are from one time point (acute
infection) and we are comparing two groups: patients with dengue hemorrhagic fever (the
severe disease) vs. dengue fever (the mild form of the disease).  The maximum coefficient of
variation between the two groups was 55%.  Assuming that for the present study the
populations to be sampled will have the same variability, a sample size of n = 25 (per group)
would guarantee 80% power at 5% significance to detect a minimum Fold-Change (FCH) of 1.5
(50% increase) when comparing two independent groups with an unpaired two-sided t-test. In
this calculation, we are taking into account that 5 pairwise comparisons will be performed, thus
the test-wise significance level will be reduced to 0.01.  
12.12   * Will samples be coded?
 Yes  
 No
If Yes, Please describe coding scheme consistent with GCP.  If samples will not be coded,
please provide justification for this proposed departure from GCP practice.
 
The blood samples for all volunteers will be coded using the IRB approval number, date, and subject
number, e.g.  TWA-0804-001.  The subject codes will be maintained in a password-protected database

on a RUH backed-up computer in the Ravetch lab that is accessed only by the Principal Investigator
and the reseach team.  
 
Once the samples are processed, the plasma will be stored in a -80C freezer in the Ravetch lab until
time of assay.
If available, upload the Data and Sample Sharing Management Plan approved by RU IT.
Version
Title
Category
Expiration
Date
Document
Outcome
Checked Out
View
Document
No Document(s) have been attached to this form.
13.0
Participants of Study
13.1   Specify age range of participants: 
* Minimum Age:
18
* Maximum Age:
80
Please note:  If the age of participants indicated is less than 18 years old, you will be
prompted to attach a Pediatric Assent form later on in the submission process.  A link to the
Pediatric Assent form can be found in the Help link to the right, or this form can be
downloaded later on in the submission process.
 
 
13.2   * Indicate the gender(s) of the participants:
Female
Male
Unknown
Not Reported
13.3   * Indicate projected enrollment by race and ethnicity.  See Help for disease/volunteer
population demographics. 
Ethnic Category
Sex/Gender
Females
Males
Unknown or
Not Reported
Total
  Hispanic or Latino
31
28
0
59
  Not Hispanic or Latino
82
74
0
156
  Unknown
  (individuals not reporting
ethnicity)
0
0
0
0
  Ethnic Category: Total of All
Subjects*
113
102
0
215
                   Racial Categories
  American Indian/Alaska Native
0
0
0
0

  Asian
14
12
0
26
  Native Hawaiian or Other Pacific
Islander
0
0
0
0
  Black or African American
38
33
0
71
  White
61
57
0
118
  More Than One Race
0
0
0
0
  Unknown or Not Reported
0
0
0
0
  Racial Categories: Total of All
Subjects*
113
102
0
215
13.4   Exclusion of Protected Groups:
*Research involving human participants should be designed/conducted to be as broadly
inclusive as possible regarding sex, gender, race, age, and ethnicity. Exclusions regarding
these characteristics require an explanation of the rationale and justification.
Will participants of a specific sex/gender/race/ethnicity/age or other protected group
characteristic be excluded from participation?
  Yes  
  No
13.5   Vulnerable Populations
Indicate whether any of the following populations will be included in the study:
Children
Pregnant Women
Cognitively Impaired Persons
RU Employees
RU Students
Other:
If you checked any of the above, give a brief explanation of the need to use these particular
individuals:
RU employees and students will be enrolled if they meet study eligibility.  Special precautions will be
used in recruiting employees and students of the Rockefeller University to minimize the possibility of
undue influence.  Rockefeller University employees will be made aware of the study through flyers
rather than directed presentations to selected groups.  Subjects will be reassured that refusal to
participate in the study will not affect their studies or employment in any way and that all medical
records will be kept in accordance with HIPAA guidelines to ensure privacy.
 
If the participant is a Rockefeller University employee, does she/he work within the Laboratory
of the Principal Investigator or Co-Investigator(s)?
Yes 
No 
N/A 
If the participant is a Rockefeller University student, does she/he work within the Laboratory
of the Principal Investigator or Co-Investigator(s)?
Yes 
No 

N/A 
13.6   *What is the total number of evaluable participants you plan to enroll at Rockefeller University Hospital
over the course of the entire study?
215
13.7   * What is the total number of participants who will need to sign consent at Rockefeller
University Hospital over the course of the entire study to result in the desired number of
evaluable participants?
278
13.8   * What is the total number of participants you plan to sign consent at Rockefeller University
Hospital in the next year?
20
13.9   * What will be the total number of evaluable participants at all sites over the course of the
entire study?
215
13.10   Inclusion Criteria
Please list participant inclusion criteria:
Order
Number
Criteria
1 
Male or Female 18-80 years of age
 
2 
Healthy volunteers without significant medical problems
 
3 
Able to give informed consent to participate
 
4 
Willing to receive a single dose of an FDA-approved vaccine (either the influnza
virus, pneumococcal or meningococcal vaccine)
 
5 
Arm III, Group 11: Prior diagnosis of dengue infection or dengue fever.
 
6 
Arm III, Group 12: Prior diagnosis of dengue hemorrhagic fever
 
7 
Arm III, Group 13: Prior diagnosis of chikungunya virus infection.
 
8 
Arm III, Group 14: Prior diagnosis of zika virus infection.
 
13.11   Exclusion Criteria
Please list participant exclusion criteria:

Order
Number
Criteria
1 
History of seizure disorder for Flumist group participants only.
 
1 
For Flumist participants: Current illness that limits delivery to nasal airway (mild illness,
such as diarrhea or mild respiratory infection with or without fever, and local infections
do not apply)
 
1 
For Flumist participants: Close contact with person with severely compromised immune
system requiring isolation
 
2 
Egg allergy for influenza vaccine groups
 
3 
Prior allergic reaction to commercial vaccination
 
4 
In the opinion of the investigator, the volunteer is unlikely to comply with the
study protocol.
 
5 
Is pregnant or lactating
 
6 
If Guillain-Barre syndrome (GBS) has occurred within 6 weeks of previous
influenza vaccination, the influenza vaccination will not be administered
 
7 
Poor venous access
 
8 
Participation in another clinical study of an investigational product currently or
within the past 90 days, or expected participation during this study.
 
9 
Any clinically significant abnormality on medical history or physical examination 
that, in the opinion of the investigator, would preclude participation.
 
10 
Received any vaccine within the last 4 weeks
 
11 
Unable to complete study
 
14.0
Schedule of Events/Study Plan
14.1   Instructions:New Studies:
The iRIS Study Plan has been phased out for new protocols. 
A Schedule of Events (below) is required for all new studies involving interactions with human
subjects.
A template Schedule of Events is available on the IRB website.  For any new study, populate the
template with the visits and procedures for the study. 
The content of the Schedule of Events should be consistent with any descriptions of study
procedures that may be in the protocol text and informed consent. 

Attach the completed Schedule of Events to the protocol below. 
Existing Studies: 
For existing studies, investigators may elect to update the existing Study Plan or may replace the Study
Plan with a Schedule of Events, following the instructions above for new studies.
Attach Schedule of Events:
Version
Title
Category
Expiration
Date
Document
Outcome
Checked Out
View
Document
1.0  
study_plan_ 
Schedule of
Events 
 
41.27 KB
Attach the Study Plan (an option only for studies with pre-existing
Study Plans):
Select a template: Template 8
 Select an arm: Screening
Procedure/Task Name
CPT Code
Screen Visit
Clinical Procedures
Adverse Event Assessment
Adverse Event /Serious Adverse Event Assessment
Assessments (Nursing)
Concomitant Medications
Height
Local/Systemic Reactogenicity Assessment
Pre- and Post Procedure Vital Signs
Vital Signs
Weight
Immunization / Vaccine
Immunization - Group 10
Immunization - Group 5 and 6
Immunization - Group 7
Immunization - Group 8 and 9
Informed Consent Process
Assess subject's knowledge and understanding of protocol
Assess subject's ongoing consent for participation
HIV Consent
Informed Consent , Obtain Initial
Informed Consent, Review for Current Date and Version
Obtain HIPAA Consent
 
 
 
1
1
1
1
 
 
1
1
1
1

Lab-Specimens: Urine
MSKCC-C - Urinalysis with Microscopic
81001
POCT - Urine Pregnancy Test
81025
Lab-Specimens: Venous Blood
MSKCC-C - AST (Aspartate Aminotransferase)
MSKCC-C - Alanine Aminotransferase (ALT), Serum
MSKCC-C - BUN, Serum
MSKCC-C - Bilirubin, Conjugated, Serum
MSKCC-C - Bilirubin, Total, Serum
MSKCC-C - CBC w/Auto Differential
MSKCC-C - Calcium, Serum
MSKCC-C - Creatinine, Serum
MSKCC-C - Electrolytes, Serum
MSKCC-C - Glucose, Serum
MSKCC-C - Hepatitis B Surface Antigen, Serum
MSKCC-C - Hepatitis C Antibody
MSKCC-C - hCG, Qualitative, Serum
Research Blood - 3 10ml Green top tubes
36415
Research Blood - 1 3.5ml SST top tube
36415
Research Blood - 1 8.5ml SST top tube
36415
Research Blood - 1.5 10ml Green top Tubes
36415
Research Blood - 12 10ml Green top tubes
36415
Research Blood - 2 8.5ml SST top tubes
36415
Research Blood - 5 8.5ml SST top tubes
36415
Research Blood - Pax Gene RNA tube
36415
Lab-Specimens: other
POCT Rapid HIV
86701-3
Medical History
Interim history
Medical History
Physical Examination
 
1
 
1
1
1
1
1
1
1
1
1
1
1
1
1
 
1
 
1
 

Physical Examination
Targeted physical examination
Procedures (Nursing)
Venipuncture
36415
Subject Teaching
Pregnancy Avoidance Counseling
CRF Forms
Administrative Procedures
1
 
1
 
1
 
 
* What is the total number of outpatient visits for all participants projected for the
next year?
75
* What is the average length of each outpatient visit (in hours)?
1
* What is the total number of Day Patient visits for all participants projected for the
next year?
0
* What is the average length of each Day Patient visit (in hours)?
0
*  What is the total number of inpatient days for all participants projected for the
next year?
0
15.0
 
Investigational and Support Medications
15.1   List all the investigational medications
See Help for link to Rockefeller University Research Pharmacy web page for additional
information.
View
Details
Drug Name
FDA Approved
IND Number
Trade Drug
Name: FluMist Vaccine
Generic Drug
Name:
Investigational
Drug Name:
Yes 
 
Trade Drug Name:
FluMist Vaccine 
Generic Drug Name:
 
Investigational Drug Name:
 

Identify the name of the
manufacturer or source of
investigational drug/biologic:
 
Is the Drug FDA Approved:
Yes  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
Are you currently using this IND
in another research project?
No  
If yes, list the IRB Number(s):
 
Dose Range:
 
Frequency:
 
Trade Drug
Name: Menveo
Generic Drug
Name:
meningococcal
conjugate
vaccine
Investigational
Drug Name:
Yes 
 
Trade Drug Name:
Menveo 
Generic Drug Name:
meningococcal conjugate vaccine 
Investigational Drug Name:
 
Identify the name of the
manufacturer or source of
investigational drug/biologic:
 
Is the Drug FDA Approved:
Yes  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
Are you currently using this IND
in another research project?
No  
If yes, list the IRB Number(s):
 
Dose Range:
 
Frequency:
 
Trade Drug
Name: Menomune
Generic Drug
Name:
Meningococcal
Vaccine
Investigational
Drug Name:
Yes 
 
Trade Drug Name:
Menomune 
Generic Drug Name:
Meningococcal Vaccine 
Investigational Drug Name:
 
Identify the name of the
manufacturer or source of
investigational drug/biologic:
 
Is the Drug FDA Approved:
Yes  
Is an IND necessary
No  
IND Number
 

Who holds the IND:
N/A  
IND details:
 
Are you currently using this IND
in another research project?
No  
If yes, list the IRB Number(s):
 
Dose Range:
 
Frequency:
 
Trade Drug
Name: Fluzone ID
Generic Drug
Name:
Influenza Virus
Vaccine
Investigational
Drug Name:
Yes 
 
Trade Drug Name:
Fluzone ID 
Generic Drug Name:
Influenza Virus Vaccine 
Investigational Drug Name:
 
Identify the name of the
manufacturer or source of
investigational drug/biologic:
 
Is the Drug FDA Approved:
Yes  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
Are you currently using this IND
in another research project?
No  
If yes, list the IRB Number(s):
 
Dose Range:
 
Frequency:
 
Trade Drug
Name: Fluzone IM
Generic Drug
Name:
Influenza Virus
Vaccine
Investigational
Drug Name:
Yes 
 
Trade Drug Name:
Fluzone IM 
Generic Drug Name:
Influenza Virus Vaccine 
Investigational Drug Name:
 
Identify the name of the
manufacturer or source of
investigational drug/biologic:
 
Is the Drug FDA Approved:
Yes  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
Are you currently using this IND
in another research project?
No  
If yes, list the IRB Number(s):
 
Dose Range:
 

Frequency:
 
Trade Drug
Name: Pneumovax 23
Generic Drug
Name:
Pneumococcal
Vaccine
Investigational
Drug Name:
Yes 
 
Trade Drug Name:
Pneumovax 23 
Generic Drug Name:
Pneumococcal Vaccine 
Investigational Drug Name:
 
Identify the name of the
manufacturer or source of
investigational drug/biologic:
 
Is the Drug FDA Approved:
Yes  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
Are you currently using this IND
in another research project?
No  
If yes, list the IRB Number(s):
 
Dose Range:
 
Frequency:
 
Trade Drug
Name: Prevnar
Generic Drug
Name:
Pneumococcal
Vaccine
Investigational
Drug Name:
Yes 
 
Trade Drug Name:
Prevnar 
Generic Drug Name:
Pneumococcal Vaccine 
Investigational Drug Name:
 
Identify the name of the
manufacturer or source of
investigational drug/biologic:
 
Is the Drug FDA Approved:
Yes  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
Are you currently using this IND
in another research project?
No  
If yes, list the IRB Number(s):
 
Dose Range:
 
Frequency:
 
15.2   * Will the study involve the use of a placebo?
  Yes  
  No

15.3   Study support medications are medications that will support the conduct of the study.  Please list all
support medications to be used in the study (include all prescription drugs, over the counter drugs herbs,
and supplements).
16.0
Consent Procedure
16.1   * This study will use the following types of informed consent:
Informed Consent Form Standard - a standard consent form with instructions for adapting it to your
study
Consent Form Genetic- a consent form designed for a study where genetic testing (as defined by
NYS law) is to be done in the CURRENT study
Consent for studies including genome wide sequencing
Pediatric Assent Form (To be used in addition to Consent) for Pediatric patients
Other (e.g., waivers, electronic informed consent)
Links to the Standard Consent, Genetic Testing Consent and the Pediatric Assent forms
can be found in the Help link to the right, or these forms can be downloaded later on in the
submission process.
16.2   * Indicate the consent process to be used.  
   (See Help for CCTS SOP)
Describe how the required information is being presented to participants (consent form, orally,
information sheet, etc.).  Attach a copy of what is being presented to participants (usually the
ICF and Assent forms).
Prior to the initiation of any study related procedures, the potential subjects will be given a copy of the
most recent IRB stamped and approved informed consent to read.  Additionally, the PI or study staff
member who has been designated to consent will discuss the specifics of the study including but not
limited to the purpose of the research, procedures, time commitment, required tasks, test article or
device, alternative treatments, benefits, risks, confidentiality etc. in a comprehensible (non-scientific)
manner, using language readily understandable by the subject. Subjects will be told that participation is
voluntary and that, if they do not consent, they will not be penalized. The person consenting will assure
the voluntariness of the subject.
Describe the circumstances under which consent will be obtained, where the process will take
place and any waiting period between informing the prospective participant and obtaining
consent. 
A private, confidential setting will be provided for the potential subject to read and discuss the informed
consent free from coercion, undue influence or constraints of time. All subjects will be given a chance to
ask questions and express concerns. They will be given the option to take the consent home and
discuss it with family, friends, and /or health care providers. After a subject and the person conducting
the consenting signs and dates the consent, the subject will be given a copy of the signed informed
consent form.
An enrollment note will be written in the source document as to who obtained consent, how, when,
were questions asked and answered, and that a copy of the informed consent was given to the subject.
Describe the experience of the investigators designated for this task in the DOA in obtaining
consent from participants.
Marina Caskey, MD, has extensive experience consenting human subjects for participation in research
studies.
Joseph Colagreco DNP, NP-BC, and Taia Wang, MD, PhD, have demonstrated competency in consenting
subjects for participation in research studies.  This competency is based on attending a consenting class
which includes regulations, the do’s and don’ts and didactic role playing.  It also includes observing the
consenting process as performed by an experienced consenter and then consenting a subject to
participate in a research study while being observed by the experienced consenter
.

How will it be determined that the participants or the participants' authorized representatives
understand the information presented? 
The "Teach Back" method will be used in the clinical research setting to ask research participants to
repeat or “teach back” the information, concepts and directions that the staff member has attempted to
convey to the subject. This method is used to assess comprehension and retention of protocol
requirements, adverse event information, risks and benefits, and the subject's rights described in the
Informed Consent process.
If English is not the participants' native language, how will written and/or verbal translation be
provided?
Spanish-speaking volunteers may be enrolled in the study. For these potential volunteers, a certified
Spanish translation of the IRB-approved informed consent form (ICF) will be used. For unexpected or
isolated volunteers who are candidates for this study, who are native speakers of other languages, a
telephonic interpreting service (such as Pacific Interpreters) will be used to facilitate the explanation of
the study. The investigator will send the interpreter a copy of the study’s ICF in the language that needs
to be interpreted.  The consenting process will be conducted by reading the English ICF while the
interpreter repeats the words in the language of choice. The interpreter will also translate questions and
answers that occur during the informed consent discussion. At the end of the consenting process, if the
participant agrees, he/she will sign the ICF in his/her native language in the presence of the
investigator. The interpreter will sign  the IRB-approved ICF  as a witness, and will fax or email the
signed copies to the investigator. The investigator will sign the IRB-approved ICF as the person
conducting the consent discussion
Will any participants be cognitively impaired so that they may not have the capacity to give
consent?
  Yes  
  No
For participants where it has been determined that they lack the capacity to give consent,
describe the provisions for obtaining consent from the participants' legally authorized
representative.
16.3   * Based on the demographics, will this study's participant population require foreign
language consent form? 
  Yes  
  No
16.4   * This study's consent procedure will require the following waivers:  
(See Help for additional information.)
Waiver of one or more elements of informed consent, 45 CFR 46.116(f) 
Waiver of documentation of informed consent, 45 CFR 46.117(c) 
No waiver is requested 
If a waiver is requested, please provide justification for the waiver here:
We are requesting a full waiver of informed consent for the use of the 150 restrospective samples
because:
1) The use of the samples involves no more than minimal risk to the subjects;
2) The waiver will not adversely affect the rights and welfare of the subjects because the subjects
consented to the future use of their samples in research;
3) The use of the samples in this research could not be practicably carried out because the RU research
team will not be provided with identifiers, and thus will not have the ability to contact subjects
16.5   Will you obtain a Certificate of Confidentiality (CoC) for this study?
  Yes  
  No
16.6   * Does this study include video/audio recording, photography or other electronic recording of
human participants?

  Yes  
  No
17.0
Recruitment and Advertising
For assistance consult CRSO to create a robust Recruitment Plan see Help.
17.1   * What is the plan for recruitment?
Overview: The CRROSS will recruit and prescreen 278 volunteers to achieve the enrollment goal of up
to 215 volunteers for vaccination. As of the April 2016 amendment, the cohort will include an additional
arm containing 100 participants in 4 groups: 25 participants with a history of dengue virus satisfying
specific laboratory criteria, 25 additional participants with a history of dengue fever or dengue
hemorrhagic fever and specific laboratory findings, 25 volunteers with a history of infection with
chikungunya, and 25 volunteers with a history of infection with Zika virus.
 
Text below is provided for the Submission Recruitment Plan:
Feasibility and Assessment:
Incentives:  1) Altruism; 2) Compensation for efforts; 3) Opportunity to receive free FDA-approved flu
vaccine
Challenges: 1) Must be able to provide documentation of the disease; 2) Participants must be willing
to return for 4 visits within 3 weeks; 3) Potential language barrier with immigrant participants who are
among the target populations
 
Issues relevant to rapid accrual: Positive: 1) Repository query yielded two potential volunteers with
a history of dengue virus infection (recruited to LBE-0910); they may be helpful stakeholders; 2) Zika,
and other tropical viral infections are currently very visible in the media raising awareness and a certain
cache; 2) Negative: It may be necessary to form partnerships with healthcare providers serving the
target populations to gain access to affected patients –  effective partnerships take time to form, and
the alignment of incentives to collaborate can be challenging, especially with a short timeline.
 
Projected enrollment timeline:  The investigator plans to see participants up to 5 days/week which
translates to screen/enrolling 1-10 volunteers a week. Assuming 1-2 weeks start up time, a few lost
weeks for vacation, amendments, or other logistics, the target for complete accrual is 12 months. The
CRSO will refer any participants prescreened through our services for further scheduling by the
investigator.
 
Recruitment Implementation:
Advertising- CRROSS will place ads both in broadly distributed NY area newspapers (i.e Metro) as well
as specific papers/platforms that are circulated among the target populations, namely individuals who
have lived in or travel to areas with high rates of infection (i.e Caribbean Life, Caribbean American
Weekly). The populations include individuals from the Dominican Republic, Puerto Rico, other Caribbean
islands, and Brazil. Demographic data from ad vendors, and demographic mapping resources, such as
http://www.nytimes.com/interactive/2011/01/23/nyregion/20110123-nyc-ethnic-
neighborhoods-map.html?_r=1& are used to target advertising efforts when possible. Other media
outlets will include internet (Voices of NY, Craigslist, Clinicaltrials.gov, centerwatch.com), radio (i.e
WBLS 107.5 FM), and others as appropriately identified.  Research Volunteer Repository Database –
The investigator has agreed to associate protocol TWA-0804 with RKO-0648, the Research Volunteer
Repository Protocol, enabling the CRROSS to query the existing volunteer database to identify a list of
potential volunteers who have agreed to be contacted for future studies and who meet basic eligibility
criteria. The CRROSS will contact potential volunteer as allowed to determine interest and will refer
eligible and interested volunteers to the study coordinator/investigator.  In parallel, the research team
will seek and document the granting or denial of permission to contact volunteers about future studies. 
Centralized Call Management – CRROSS will work with the research team to develop a protocol-
specific pre-screening script based on IRB approved protocol eligibility criteria to prescreen volunteers
who call 1800RUCARES. Potentially eligible candidates will be scheduled for the study team for further
screening. CRROSS staff will also call volunteers based on Repository queries described above. Research
teams are responsible to provide timely updates on pre/screening outcomes (through iRIS, etc.) to keep
CRSO strategies on target.
 
Patient referral from Elmhurst Hospital, Queens, NY:
Doctors from Elmhurst Hospital, Joseph Masci and Maurice Policar, will refer interested individuals who
have appropriate medical histories for Arm III to CRROSS for pre-screening.
 
 
 

17.2   *From the date of final IRB approval, how long will it take to complete
enrollment of the study?
6 Months 
12 Months 
18 Months 
24 Months 
More than 2 years (specify in years) 
10 years
17.3   This Study
Involves an intervention or comparison and a defined enrollment target 
Is a natural history study with expected annual enrollment over many years 
Is an exploratory mechanistic study 
Other 
17.4   This Study will enroll:
Healthy volunteers 
Individuals affected with a specific disease/disorder 
Both 
17.5   * Do you plan on using the Research Participant Repository (RKO-0648) ?
 Yes  
 No
17.6   * Are you screening or recruiting from or through a record review of an existing patient
database of a healthcare provider? 
 
  Yes  
  No
17.7   * Please describe how the Recruitment Plan addresses recruitment of the volunteers
consistent with the demographics of the condition under study:  
Recruitment is intended to yield volunteers from a variety of ethnic and socioeconomic backgrounds
from the age range specified
17.8   * Do you plan to advertise directly to potential volunteers?  (As opposed to relying on
practitioner referrals  or flyers to practitioners)
 Yes  
 No
17.9   * Do you plan to use the free, web-based volunteer registry, ResearchMatch.org, as a
recruitment tool?
 Yes  
 No

18.0
Research Participant Repository (RKO-0648)
18.1   This protocol, will be linked with the Research Volunteer Screening/Recruitment Data Repository run by
the Recruitment staff and the Clinical Research Support Office (protocol RKO-0648-1008).   In order to
participate in the generation of the Repository the PI will enter into a Collector/Collaborator agreement
regarding the Repository. The role of Collector/Collaborator is to contribute to the Repository the name,
contact and demographic information, recruitment referral information, and screening outcome
information, as well as appropriate protocol specific screening information, of volunteers who are screened
by telephone or in person for entry into the protocol regardless of the screening outcome. In addition to
screening volunteers for the PI's current study, verbal consent will be obtained from the volunteers
regarding their willingness to be contacted in the future about possible additional research studies. This
permission may be obtained by the Recruitment office staff through the central Call Center.  If the  PI
receives calls directly from participants for initial prescreening, then the PI is responsible for collecting the
required information and conveying it to the Recruitment staff for data entry.  The consent or withholding
of permission will be recorded in the Repository as will the name of the person who obtained the
permission. A volunteer’s permission or declination will not affect their eligibility for my current protocol,
or future protocols. The Recruitment staff of the Clinical Research Support Office may gather the
Repository information and request the verbal consent of the volunteer for re-contacting on my behalf as
part of our recruitment plan.   In order to benefit from the Repository,  the PI will enter into a
Recipient/Collaborator agreement with the Repository.  The Recipient/Collaborator may receive from the
Repository pre-screened lists of potentially eligible participants for his/her study as a means to facilitate
recruitment. The Recruitment staff will prepare the Repository queries according to the protocol eligibility
requirements and available Repository information, and may re-affirm permission to re-contact volunteers
as necessary. The PI may use the information and names in the list from the Repository only for the
current study and may not save the list to use for a future study of his/her own, nor may he/she share the
list with colleagues for other studies."
19.0
Utilization of ResearchMatch.org 
19.1   Utilization of ResearchMatch.org for Recruitment
 
Basic information regarding this tool:
 
ResearchMatch.org is a national electronic, web-based recruitment tool that was created through
the Clinical & Translational Science Awards Consortium in 2009 and is maintained at Vanderbilt
University.  There is no cost for researchers at participating institutions in the ResearchMatch.org
Network to use ResearchMatch.org. The Vanderbilt IRB provides oversight for ResearchMatch.org as
a recruitment tool and this has been documented within the ResearchMatch.org IRB Letter of
Understanding which was executed by Dr. Gotschlich in October, 2009.  However, individual
requests to use ResearchMatch.org as a recruitment tool must be submitted to this institutions’ IRB.
Registration:
 
This recruitment tool may be utilized once the PI or research staff registers for recruitment access
through ResearchMatch.org and the Institutional Liaison provides approval.
The ResearchMatch.org Institutional Liaison will review the study information and evidence of IRB
approval. He/she will set the researcher’s expiration date to mirror that of the study’s IRB approval.
Search Capability:
 
After being granted recruitment access, the researcher can search for appropriate matches amongst
the non-identifiable ResearchMatch.org Volunteer profiles in the system.  He/she can enter study
inclusion/exclusion criteria in the ResearchMatch.org Search Builder which will yield a list of
potential matches to the study’s criteria. 
Contacting ResearchMatch.org Volunteers:
 
Once yielding a list of potential matches (ResearchMatch.org Volunteers), the researcher will send
out IRB-approved content that will be the initial recruitment message that these volunteers receive
about the study through ResearchMatch.org. The study’s recruitment message will be inserted into
the standard ResearchMatch.org electronic notification that informs possible matched Volunteers
that he/she has been identified as a potential match for the study.  The secure ResearchMatch.org
clearinghouse will route this standard ResearchMatch.org email notification. These potential
matching volunteers will have the option of replying yes, no, or not respond through a set of quick
links available in this notification to the study announcement. THE CONTACT MESSAGE WILL NOT
INCLUDE THE STUDY’S DIRECT CONTACT INFORMATION (e.g. EMAIL, PHONE).  By responding yes,
the Volunteer has authorized ResearchMatch.org to release his/her contact information to the
researcher.  The researcher will be responsible for managing this contact information as called for
by this IRB-approved study protocol. 

Study Management in ResearchMatch.org:
 
Researchers (and the Liaison) can view information regarding his/her study’s status in
ResearchMatch.org (e.g. number of volunteers contacted for the study via ResearchMatch.org to
date, response rate of volunteers, etc.).  ResearchMatch.org will also be collecting aggregate data
regarding the status of ResearchMatch.org volunteers within the study. Volunteers consent to this
within the ResearchMatch.org Volunteer Agreement. This information will allow the researcher to
indicate where the Volunteer currently stands within the recruitment process and thus will help the
researcher monitor the utility and effectiveness of using this resource (e.g. Did not contact, Not
eligible, Enrolled, Completed, etc.).
20.0
Potential Benefits to Participants
20.1   * Will participation in this study provide direct benefits to the participant?
 Yes  
 No
20.2   If Yes, describe the potential direct benefits:
Volunteers will receive without cost an FDA-approved vaccine.
21.0
Potential Risks to Participants
21.1  
*  Describe any potential risks: physical, psychological, social, legal or other and assess their
likelihood and seriousness. Indicate risks both to the participants and to the embryo or fetus
if the participant is or may become pregnant.  Please provide the potential risks below:
Blood draw:the risks associated with a blood draw are generally minor.  They are mild pain at the
needle site (common), local bruising at needle site (rare), infection and fainting (extremely rare).
 
Influenza Vaccine (IM administration):
·         Most common (≥10%) injection-site reactions were injection site tenderness, pain, swelling and
arm stiffness.
·         Most common (≥10%) systemic adverse events were headache and myalgia.
·         Life-threatening allergic reactions from vaccines are very rare. If they do occur, it is usually
within a few minutes to a few hours after the shot.
·         In 1976, a type of inactivated influenza (swine flu) vaccine was associated with Guillain-Barré
Syndrome (GBS). Since then, flu vaccines have not been clearly linked to GBS. However, if there is a
risk of GBS from current flu vaccines, it would be no more than 1 or 2 cases per million people
vaccinated. This is much lower than the risk of severe influenza, which can be prevented by vaccination.
 
Influenza Vaccine (ID administration):
·         The most common injection-site reactions were erythema (>75%) induration (>50%), swelling
(>50%), pain (>50%), and pruritus (>40%). Erythema, induration, swelling and pruritus occurred
more frequently following intradermal administration.
·         The most common solicited systemic adverse events were headache, myalgia, and malaise
(>20%).
 
Flumist Vaccine (Intranasal administration):
·         The most common solicited adverse reactions were runny nose or nasal congestion (44%) and
sore throat (19%).
 
Meningococcal Vaccine (Menveo):
·         In clinical trials, the most frequently occurring adverse events (≥10%) in subjects 11 to 55 years
of age who received Menveo were pain at the injection site, headache, myalgia, malaise, and nausea.
·         You should not receive Menveo if you have had a severe allergic reaction to any ingredient of the
vaccine, or if you have had a severe allergic reaction to a vaccine containing similar components as
Menveo.
·         Following vaccination with another US-licensed meningococcal conjugate vaccine, an evaluation
of postmarketing adverse events suggested a potential for increased risk of Guillain-Barré Syndrome
(GBS). There is not enough information to evaluate if a risk of GBS exists following administration of
Menveo.

·         Serious allergic reactions, within a few minutes to a few hours of the shot, are very rare.
 
Meningococcal Vaccine (Menomune):
·         Common (>10%) adverse events in persons 11 to 55 years of age were pain, redness, and
induration at the injection site, headache, fatigue, malaise, arthralgia, and diarrhea.
·         Serious allergic reactions, within a few minutes to a few hours of the shot, are very rare.
 
Pneumovax Vaccine (Pneumovax 23)
·         The most common adverse reactions, reported in >10% of subjects were: injection-site
pain/soreness/tenderness (60.0%), injection-site swelling/induration (20.3%), headache
(17.6%), injection-site erythema (16.4%), asthenia and fatigue (13.2%), and myalgia
(11.9%).
 
Pneumovax Vaccine (Prevnar):
·         In adults aged 50 years and older the commonly reported solicited adverse reactions were pain
at the injection site (>50%), fatigue (>30%), headache (>20%), muscle pain (>20%), joint pain
(>10%), decreased appetite (>10%), injection site redness (>10%), injection site swelling (>10%),
limitation of arm movement (>10%), chills (>5%) or rash (>5%).
22.0
Procedures to Minimize Risks
22.1   * Describe the procedures for protecting against or minimizing any potential risks, and
include an assessment of their likely effectiveness. Include a discussion of confidentiality
safeguards, where relevant, and arrangements for providing medical treatment, if needed.
Volunteers will be monitored for a minimum of 20 minutes after receiving their vaccination
Volunteers will receive a telephone call or email from a member of the research staff 2 weeks
(+/- 2 days) after receiving their vaccination to assess for side effects to the vaccination.  If a
volunteer complains of any moderate greater adverse event, they will be asked to return to the
outpatient clinic for an evaluation
All blood will be drawn by licensed professionals using sterile technique
23.0
Alternative Methods or Treatments
23.1   * Describe alternative methods or treatments for the disease(s) under study, if any, that were
considered and why they will not be used:  
A volunteer may choose not to participate in this study
24.0
Data and Safety Monitoring
This section describes the Data and Safety Monitoring Plan (DSMP)
required of each protocol undertaken at the CCTS according to HRPP
and NIH policies Notice 98 -084 and Notice 00-038, as cited in Help
Sections below.   Depending on the level or risk and trial phase, some
protocols will need Data and Safety Monitoring Boards.
24.1   * Overall Risk Classification
An estimate of risk is necessary to evaluate the adequacy of the planned monitoring.  The
HELP section provides guidance in making the risk assessment. 
Read the risk definitions and examples of risk in the HELP section and select the risk
category that best describes the current study. 
If your assessment differs from the definitions the HELP section, describe any factors that
modify your judgment of the overall risk in the text box after the risk designation.

MINIMAL RISK 
LOW RISK 
MODERATE RISK 
SIGNIFICANT RISK 
Please provide any optional description(s):
24.2   Protocols Involving Minors
The chance of direct benefit to the child, or to understanding a disorder not otherwise
understood, may be major factors in justifying more than minimal risk in research involving
children.  
Based on the above definitions, please specify your study's risk classification below:
NOT GREATER THAN MINIMAL RISK (the risk of daily life to a healthy child living in a safe
environment) 45 CFR 46.404 
GREATER THAN MINIMAL RISK WITH DIRECT BENEFIT TO PARTICIPANT; 45 CFR 46.405 
GREATER THAN MINIMAL RISK, NO DIRECT BENEFIT, BUT BENEFIT TO UNDERSTANDING OF
PARTICPANT'S DISORDER; 45 CFR 46.406 
RESEARCH NOT OTHERWISE APPROVED PRESENTING OPPORTUNITY TO UNDERSTAND, PREVENT
OR ALLEVIATE SERIOUS PROBLEM AFFECTING CHILDREN 45 CFR 46.407 (cannot be approved by
IRB; requires public comment) 
24.3   DSMB
1. The NIH requires that all SIGNIFICANT RISK protocols have a Data and Safety
Monitoring Board and provide information about the expertise and independence of
that Board
2. Phase III trials require a Data and Safety Monitoring Board,
3. A DSMB may be appropriate for some Phase I and II protocols. (See Help for
examples.)
4. It is the investigator's responsibility to report to the IRB, the findings and
recommendations of the DSMB as they become available.
Please specify:
A DSMB is required for this study 
A DSMB is not required for this study 
Unsure 
If a DSMB is not required, but is being constituted for other reasons, please explain:
24.4   * Safety Review
Select one:
Safety Review is conducted as follows: Laboratory results for research volunteers will be reviewed in
a timely manner, usually within 24 hours of receipt by a licensed practitioner. The potential clinical
significance of any abnormal finding will be documented in the medical and research record(s), and
an appropriate plan or referral developed. The PI's review of safety issues at research team rounds
will be documented in the meeting minutes. 

Protocol Specific 
24.5   Monitoring
Monitoring Personnel:  See Help Bubble to the right.
Internal Monitoring
The PI or his/her designee shall conduct internal monitoring to assure the safe and proper
conduct of the protocol and all the elements list above in monitoring, following the general
principles of quality management.  The intensity and frequency of internal monitoring will
depend on the protocol risk to participants, the experience of the PI and research team, rate
of enrollment, and specific details of the protocol. 
Internal monitoring of informed consent and eligibility documentation will be conducted by the
research team shortly after enrollment begins.  Internal monitoring activities will be
documented by logs, meeting minutes or other systematic means.  
Specify the research team members who will conduct the internal monitoring of the study (see
Help for who may monitor):
All members of the study team (Taia Wang, MD, PhD, Marina Caskey, MD, and Joseph Colagreco, DNP,
NP-BC) will meet regularly to discuss any protocol, volunteer, recruitment and regulatory issues.
For new investigators:  Internal monitoring should be conducted at least monthly by new
investigators until there are essentially no findings to correct at each review.
External Monitoring
*  Is external monitoring planned for this protocol?
Yes 
No 
Unsure 
If external monitoring is planned, please specify (see Help for who may monitor):
(Significant Risk) External monitoring will occur at least every six weeks unless there is no
enrollment 
(Moderate Risk) External monitoring will occur at least quarterly 
(Low or Minimal Risk) External monitoring will occur at least annually 
If external monitoring is planned, please specify the name of the monitor:
Note that copies of external monitoring reports must be supplied to the IRB and the CRSO as soon
as they are made available
Additionally, audits of the research records of minimal, moderate or significant-risk protocols
may be performed by the CRSO staff on a random basis or as part of a prospectively identified
auditing plan. 
24.6   Adverse Event Classification
Adverse events are classified by definition, severity, and association with the investigational trial.
 
Definition of an Adverse Event
Any unfavorable or unintended sign (including abnormal lab findings), symptom or disease temporally
associated with the use of a medical treatment or procedure, or protocol,  regardless of whether it is
considered related to the medical treatment or procedure or protocol.
 
Definition of a Serious Adverse Event
Any unanticipated event that involves the following:

o   results in death
o   is life-threatening
o   requires hospitalization or prolongs existing hospitalization
o   results in persistent or significant disability/incapacity
o   is any medical event which requires treatment to prevent one of the outcomes listed above
Other events can be classified as "serious adverse events" at the discretion of the PI.
 
Definition of Anticipated/Expected Adverse Event
Any adverse event, which has been reported in the Investigator's Brochure, package insert, safety reports,
clinical protocol, consent form or listed in the NCI agent-specific Expected Adverse Event List3, is classified as
an expected adverse event.  The investigator must provide the available data of known adverse events and
toxicities that have been associated with the study drug, device, intervention, or procedures.  This information
helps to define the level of risk of the trial and enables safety monitoring.  A minimal risk trial may not have
any defined risks and a statement to that effect is sufficient to meet the DSMP requirements.
 
Definition of an Unanticipated/Unexpected Adverse Event
Any adverse event that is not consistent with the known, predicted possible effects of the research protocol. 
An unexpected adverse event varies in nature, intensity or frequency from information on the investigational
product provided in the Investigator's Brochure, package insert, safety reports, clinical protocol, or listed in
the consent form.
 
Definition of an Unanticipated Problem (UaP)
A UaP is an event or circumstance that meets all the following three criteria: [1] the nature, severity,
frequency of the event(s) or information was not expected in the descriptions in the study documents or the
characteristics of the participant population being studied; [2] there is a reasonable possibility that the
procedures involved in the research caused or are linked in a significant way to the problem; [3]the event or
information suggests that the research places particpants or others at a greater risk of harm than was
previously known or recognized (including physical, psychological, economic, or social harm.
 
 
Grade and Relatedness of Adverse Events:
Adverse Events are graded for severity and scored for relatedness to the protocol, according to a published
scale.  Several standardized AE Reporting scales are available.  (See Help for links to these scales.)  
* Please indicate the scale you intend to use:
CTC v2.0 ( http://ctep.info.nih.gov/reporting/ctc.html ) 
CTCAE v3.0 ( http://ctep.info.nih.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf) 
CTCAE v4.0 (http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf) 
CTCAE v5.0
(https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf) 
AIDS Clinical Trials Group (http://aactg.s-3.com/) 
Other 
24.7   Reporting Adverse Events
All AEs will be reported to the IRB at least annually.
Reporting Serious AEs
Serious Adverse Events, (SAEs) will be reported to the IRB according to policy, within two working
days of identification of the SAE.
Select all that apply:
SAEs will be reported to the Sponsor and or ESCROW
SAEs will be reported to the sponsor within how many days of the event?

 
SAEs will be reported directly to the FDA, per 21 CFR 312
      SAEs must be reported directly to the FDA within 7 days of the event by the
investigator/sponsor.
SAEs will be reported to another entity
Describe:
Reporting Unanticipated AEs:
Select all that apply:
UAEs will be reported to the IRB
UAEs that are related and greater than moderate severity must be reported to the IRB
according to policy, within two working days of identification of the UAE. 
 
UAEs will be reported to the Sponsor
UAE will be reported to the sponsor within how many days of the event?
UAEs will be reported to the FDA, per 21 CRF 312
UAEs will be reported to the FDA, per 21 CRF 312, within 15 days.
UAEs will be reported to another entity
Describe:
24.8   Reporting Unanticipated Problems
Unanticipated problems involving risks to participants or others will be reported to the IRB and the
CRSO within five working days.
24.9   CLIA/CLEP
 
Only laboratory and research tests that are CLIA/CLEP certified or waived may be used to
determine eligibility, shared with research volunteers, and used in clinical decision making.
Select if applicable:
This study includes tests that are not CLIA/CLEP certified; the results of such tests will not be used
in clinical decision making, or to determine eligibility, or shared with participants or their health care
providers.
24.10   Tissue Repository
Human Tissue and Data Repositories collect, store, and distribute human tissue materials
and or data for research purposes. Repository activities involve three components: (i) the

collectors of tissue samples\data;  (ii) the repository storage and data management center;
and (iii) the recipient investigators.
*  Select one:
I DO NOT intend to collect, store, and distribute human tissue materials for research purposes 
I DO intend to collect, store, and distribute human tissue materials for research purposes, therefore
this protocol entails the Operation of a Tissue Repository. The IRB requires that the protocol specify
the conditions under which data and specimens may be accepted and shared, and ensuring
adequate provisions to protect the privacy of participants and maintain the confidentiality of data. 
If you do intend to collect, store, and distribute human tissue materials, you will be asked to
upload the following documents later on in the submission:
A Sample collection protocol (for tissue collector collaborators to follow) and informed
consent document for distribution to tissue collectors and their local IRBs.
A Certificate of Confidentiality (to protect confidentiality of repository specimens and
data).
A Recipients Agreement describing the commitment of the recipient to preserve the
anonymity of the samples shared.
25.0
Toxicity Management and Stopping Rules
25.1   * Describe any drug toxicity or other conditions under which the participation of a
participant or the conduct of the study would be stopped in order to maximize safety (e.g.,
toxicity management and stopping rules):
 
Not applicable.
* Indicate withdrawal criteria and procedures below:
Volunteers may be involuntarily withdrawn from the study if:
- They fail to keep appointments.
- Termination or cancellation of the research study by the investigator or the Rockefeller University
Institutional Review Board.
- There is a significant adverse event to the participant or to others in the study,
26.0
Compensation/Costs
26.1   *Will any compensation be offered to participants in return for their participation, e.g., direct
payment, medical care, tests, etc.?  
No 
Yes (Please describe) 
Please Describe
Volunteers will be compensated $75 for their vaccine visit, $35 for the follow-up blood draw visits
except for the final visit at week 12, for which participants will be compensated $75. Participants who
return for the 6-12 month visit will be compensated $50.
It is expected that volunteers for Arm 3 will be more likely to live outside of the immediate area, as
patients with prior flavivirus or alphavirus infection are relatively rare. In consideration of anticipated
travel time for volunteers in Arm 3, participants will receive $25 for the screening visit, and

compensation will be a minimum of $100 for each visit.
26.2   * Will there be any costs to participants associated with their participation in research?
  Yes  
  No
27.0
Bibliography
27.1    Enter your bibliography below:
References:
 
1.         Anthony RM, Wermeling F, Ravetch JV. Novel roles for the IgG Fc glycan. Annals of the New York
Academy of Sciences. 2012 Apr;1253:170-80. PubMed PMID: 22288459. Epub 2012/02/01. eng.
2.         Nimmerjahn F, Ravetch JV. Antibody-mediated modulation of immune responses. Immunological
reviews. 2010 Jul;236:265-75. PubMed PMID: 20636822. Epub 2010/07/20. eng.
3.         Arnold JN, Wormald MR, Sim RB, Rudd PM, Dwek RA. The impact of glycosylation on the
biological function and structure of human immunoglobulins. Annual review of immunology.
2007;25:21-50. PubMed PMID: 17029568.
4.         Kaneko Y, Nimmerjahn F, Ravetch JV. Anti-inflammatory activity of immunoglobulin G resulting
from Fc sialylation. Science. 2006 Aug 4;313(5787):670-3. PubMed PMID: 16888140.
5.         Rademacher TW, Williams P, Dwek RA. Agalactosyl glycoforms of IgG autoantibodies are
pathogenic. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6123-7. PubMed PMID: 8016124. Pubmed
Central PMCID: 44150.
6.         Shields RL, Lai J, Keck R, O'Connell LY, Hong K, Meng YG, et al. Lack of fucose on human IgG1
N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular
toxicity. The Journal of biological chemistry. 2002 Jul 26;277(30):26733-40. PubMed PMID: 11986321.
7.         Anthony RM, Nimmerjahn F, Ashline DJ, Reinhold VN, Paulson JC, Ravetch JV. Recapitulation of
IVIG anti-inflammatory activity with a recombinant IgG Fc. Science. 2008 Apr 18;320(5874):373-6.
PubMed PMID: 18420934. Pubmed Central PMCID: 2409116.
8.         Okazaki A, Shoji-Hosaka E, Nakamura K, Wakitani M, Uchida K, Kakita S, et al. Fucose
depletion from human IgG1 oligosaccharide enhances binding enthalpy and association rate between
IgG1 and FcgammaRIIIa. Journal of molecular biology. 2004 Mar 5;336(5):1239-49. PubMed PMID:
15037082.
9.         Umana P, Jean-Mairet J, Moudry R, Amstutz H, Bailey JE. Engineered glycoforms of an
antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity. Nature
biotechnology. 1999 Feb;17(2):176-80. PubMed PMID: 10052355.
10.       Selman MH, de Jong SE, Soonawala D, Kroon FP, Adegnika AA, Deelder AM, et al. Changes in
antigen-specific IgG1 Fc N-glycosylation upon influenza and tetanus vaccination. Molecular & cellular
proteomics : MCP. 2012 Apr;11(4):M111 014563. PubMed PMID: 22184099. Pubmed Central PMCID:
3322571.
11.       Selman MHJ, de Jong SE, Soonawala D, Kroon FP, Adegnika AA, Deelder AM, et al. Changes in
Antigen-specific IgG1 Fc N-glycosylation Upon Influenza and Tetanus Vaccination. Molecular & Cellular
Proteomics. 2012 Apr;11(4). PubMed PMID: ISI:000302786500015. English.
12.       Chen FW, Cannon LE, Margolies MN, Strosberg AD, Haber E. Purification, specificity, and
hypervariable region sequence of anti-pneumococcal polysaccharide antibodies elicited in a single
rabbit. J Immunol. 1976 Sep;117(3):807-13. PubMed PMID: 8570.
13.       Perlmutter RM, Hansburg D, Briles DE, Nicolotti RA, Davie JM. Subclass restriction of murine
anti-carbohydrate antibodies. J Immunol. 1978 Aug;121(2):566-72. PubMed PMID: 79606. Epub
1978/08/01. eng.
14.       Darcy E, Leonard P, Fitzgerald J, Danaher M, O'Kennedy R. Purification of antibodies using
affinity chromatography. Methods in molecular biology. 2011;681:369-82. PubMed PMID: 20978976.
Epub 2010/10/28. eng.
15.       Collin M, Olsen A. EndoS, a novel secreted protein from Streptococcus pyogenes with
endoglycosidase activity on human IgG. The EMBO journal. 2001 Jun 15;20(12):3046-55. PubMed
PMID: 11406581. Pubmed Central PMCID: 150189. Epub 2001/06/19. eng.
16.       Usinger WR, Lucas AH. Avidity as a determinant of the protective efficacy of human antibodies
to pneumococcal capsular polysaccharides. Infection and immunity. 1999 May;67(5):2366-70. PubMed
PMID: 10225896. Pubmed Central PMCID: 115979. Epub 1999/05/04. eng.
17.       Saeland E, Jakobsen H, Ingolfsdottir G, Sigurdardottir ST, Jonsdottir I. Serum samples from
infants vaccinated with a pneumococcal conjugate vaccine, PncT, protect mice against invasive infection
caused by Streptococcus pneumoniae serotypes 6A and 6B. J Infect Dis. 2001 Jan 15;183(2):253-60.
PubMed PMID: 11110649. Epub 2000/12/09. eng.
18.       Treanor JJ, Tierney EL, Zebedee SL, Lamb RA, Murphy BR. Passively transferred monoclonal
antibody to the M2 protein inhibits influenza A virus replication in mice. J Virol. 1990 Mar;64(3):1375-7.
PubMed PMID: 2304147. Pubmed Central PMCID: 249260. Epub 1990/03/01. eng.

19.       Smith P, DiLillo DJ, Bournazos S, Li F, Ravetch JV. Mouse model recapitulating human Fcgamma
receptor structural and functional diversity. Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6181-6.
PubMed PMID: 22474370. Pubmed Central PMCID: 3341029. Epub 2012/04/05. eng.
 
28.0
Appendices
28.1   Enter your appendices below:
None
29.0
Funding
29.1   * Do you have sufficient financial resources to support your study? 
 Yes  
 No
29.2  
If this study is/was pilot funded, please specify dates of funding:
From date:
12/04/2015
To date:
06/30/2016
29.3   Source of investigational agents:
N/A (no investigational agents) 
Provided by a pharmaceutical sponsor/partner with funding as described below 
Provided by a pharmaceutical sponsor/partner without additional funding 
Provided by investigator, participants, or other 
29.4   Specify funding by Rockefeller University, industry sponsor and/or grant:
   Search for a sponsor   
 Sponsor
Funding
Rockefeller
University
  Ravetch Laboratory
Industry
 
Grant
  NIH/NIAID

Pilot
Award
 

29.5   List grants in which this study is named:
PHS or
Non-PHS
Program
Grant Number
Grant Name
From Date
To Date
PHS
NIH/NIAID
1U19AI111825-
01
Integrating
innate and
adaptive
pathways in
vaccine
responses
04/01/2019
03/31/2024
PHS
NIH/NIAID
U19AI109946-
01
Mechanisms
of broadly
neutralizing
humoral
immunity
against
influenza
viruses
05/01/2014
04/30/2019
30.0
Clinical Services
30.1   *What is the general health status of your study group(s)?
Well/Minimally Ill
Moderately Ill
Severely Ill
Other
Not Applicable
If other than Well/Minimally Ill, please describe:
30.2   * Does your study group have special care needs? 
  Yes  
  No
30.3   * Does your study have special equipment needs? 
  Yes  
  No
30.4   * Will you require storage space on the clinical units for supplies to conduct this study?
  Yes  
  No
30.5   * Is special training of hospital staff required?
  Yes  
  No

31.0
Pharmacy Services
31.1   * Does the study require Pharmacy Services?
 Yes  
 No
If Yes, please proceed to next section.
31.2   Types of pharmacy services required:
Dispensing
Randomization
Compounding
Other
31.3   Dispensing:
Sponsor supplied drugs
Pharmacy supplied drugs
Other
31.4   Type of medication(s):
Injectable
Ophthalmic
Inhalational
Topical
Suppository
Other
If Injectable, please specify:
Monday-Friday 8:30AM-5PM
Off-hours [all other days/times]
32.0
Bionutrition
32.1   * Will study require patient meals? 
  Yes  
  No
If Yes, please specify:
Type of Diet
In/Outpatient
Pack Meal
Standard
Inpatient
Outpatient
Pack Meal 
Therapeutic
Inpatient
Outpatient
Pack Meal 

Research Diet
Inpatient
Outpatient
Pack Meal 
Formula Diet
Inpatient
Outpatient
Pack Meal 
Nutrient(s) to be controlled (specify):
32.2   Will meal times be altered? 
  Yes  
  No
If Yes, please explain:
32.3   Does the protocol require any of the following activities?
Food Frequency Questionnaire
Bod Pod/ Anthropometric Measurements
Diet History/ Food Records
Diet/ Nutrition Education
32.4   Will food be provided to caregiver, parent or significant other?  
  Yes  
  No
32.5   For metabolic diets, is diet homogenization required for nutrient analysis
 by independent lab?
Yes 
No 
N/A 
33.0
Clinical and Translational Research Facilitation Office
33.1   Indicate navigation assistance requested and/or received in the development of the study:
Requested
Received
Protocol Development
Protocol Implementation
Protocol Conduct
ACCTS/IRB Submission

33.2   Indicate additional education assistance requested and/or received in the development of the study:
Requested
Received
IND
IDE
Team Science Education
Study Progress Meeting
Investigator
Responsibilities
Regulatory Binder/Folder
Source Documentation
Participant Involvement in
Research
34.0
Clinical Research Support Office Resources (CRSO)
34.1   Indicate regulatory input assistance requested and/or received in the development of the study:
Regulatory Support/Design
Requested
Received
General,
Vulnerable Populations,
Minors, Group Harms
IND/IDE advice,
assistance, and referral
Informed Consent/Assent
Data Safety Monitoring
Plan

Clinical Trial Registration
Plan For Return of
Research Results
Audit/Monitoring Service,
Referrals, SOPs
34.2   Indicate recruitment assistance requested and/or received in the development of the study:  
Recruitment of Participants
Requested
Received
Recruitment Planning and/or
written Plan
Advertising Strategy, Content,
Placement
Repository/Research Match
Queries
Call
Center/Prescreening/Scheduling
Cost Sharing for Advertising
34.3   Indicate community engaging assistance requested and/or received in the development of the study:
Community Engagement
Requested
Received
PHI Statement/Engaging
Stakeholders Section
CEnR Navigation – fostering
pt/community partnership
Outreach to
community/partner/advocacy
group/CE Studio
34.4   Indicate other assistance requested and/or received in the development of the study:

Other
Requested
Received
Survey design, fielding,
validation
Data transfer and security
planning
35.0
BERD: Biostatistics, Epidemiology and Research
Design Resource
35.1   Indicate the Biostatistical assistance requested and/or received in the development
of this study:
Requested
Received
Development of
experimental design
Power analysis/Sample
size determination (# of
subjects)
Navigation (Did
Statistician participate in a
navigation meeting)
Randomization schedule
Data analysis
Development of new
statistical techniques for
data analysis (Statistical
research)
Protocol implementation
Other
35.2   If you are/will be using data analysis specify:

Exploratory
Descriptive
Hypothesis testing
Statistical modeling
Other
35.3   If you are/will be assisted with protocol implementation, specify:
Publication
Conference
Other (type of dissemination)
Grant(s)
35.4   Please select the Biostatistician on this Protocol:
Roger Vaughan, DrPH
Caroline Jiang, MS
Sandra Garcet, PhD
Adam Qureshi, MA
Other
36.0
Biomedical Informatics Resources
36.1   Indicate Bioinformatics assistance requested and/or received in the development of this study:
Requested
Received
Microarray analysis
Pathway analysis
RNA-seq analysis
Bioinformatics training and
consultation
Bioinformatics
experimental design
HPC computing
Other

36.2   If you are/will be using pathway analysis software, specify:
Ingenuity IPA
David
GSEA
Other
36.3   If you are/will be using RNAseq analysis software, specify:
Tophat
Cufflinks
Cuffdiff
CummRbund
STAR
featureCounts
DESeq2
VOOM
RNA-SeQC
If other, specify:
36.4  
Indicate Medical Informatics assistance requested and/or received in the development of this study:
Requested
Received
Data storage inside of iRIS
Redcap Database
Custom or Ad Hoc reports
Study plan creation
Specialize database or
custom software
Other
37.0
HIPAA Form
37.1   A study's specific HIPAA form signed by the volunteer is required for institutions that are
HIPAA covered entities so that they may communicate Private Health Information (PHI) to the
Investigator.  

Below, Memorial Sloan Kettering Cancer Center, New York-Presbyterian Hospital and Weill
Medical College of Cornell University are listed so that that they may report laboratory
results and X-ray readings respectively.  If you foresee that any other entity may need to
provide PHI then add them to the field highlighted in green.
37.2   Name of Study:     
An open label study of IgG Fc glycan composition in human immunity
37.3   Principal Investigator:
Taia Wang, MD, PhD
37.4   Industry Sponsor:
If the funding source is industry please type in the sponsor here
Who may obtain, use, and/or disclose your health information?
The following persons and organizations may obtain, use, or disclose health information about you.
The Principal Investigator(s) listed at the top of this form, and persons who assist the
Investigator(s) in carrying out the research
Each research site for this study, including The Rockefeller University, and the research
management and support staff and the medical staff at each site
Health care providers who have provided in the past, or currently provide, health care services
to you
Laboratories and other persons and organizations that will analyze your health information
and/or biological samples as part of this study, including Memorial Sloan Kettering Cancer
Center, New York-Presbyterian Hospital and Weill Medical College of Cornell University
Other entities that may need to provide PHI:
Members and staff of the Institutional Review Board and other boards and committees that
watch over research at The Rockefeller University 
Members and staff of The Rockefeller University's Office of Sponsored Research
The sponsor(s) of the research, named above, and persons who watch over the research for the
sponsor(s)
The United States Food and Drug Administration, other government agencies, regulatory entities
and Rockefeller University consultants that watch over the safety, effectiveness, and quality of
research and/or fund The Rockefeller University Hospital
Others (as described here):
What information will be obtained, used, or disclosed?   
The persons and organizations listed above may obtain, use, and disclose:  
Information about you that is created or collected during the research study (but not including
any HIV-related information) 
Health information in your medical records that is relevant to the research study (but not
including any HIV-related information)
And, if checked below:
 
___ HIV-related information (this includes any information indicating that you have had an HIV-
related test or have HIV infection, HIV-related illness, or AIDS, as well as information that could

indicate you may have been exposed to HIV) 
___ Other information (as described here):
                                                                                                                                              
                                                                                                                                              
                                                                                                                                              
                                                                                                                                               
Other information (as described here):
 
By signing this form, you give permission to the persons and organizations listed above to obtain, use
and disclose your health information noted above. 
 
 
How will your health information be used?
 
The health information noted above, as well as information shown by the boxes checked above (if
any), may be obtained, used, and disclosed: 
to conduct the research study explained to you during the informed consent process; and
to assure the quality, safety, and effectiveness of the research study 
 
Please note that the persons and organizations listed above may re-use or further disclose your
information if they are permitted by law to do so.
 
 
What are your rights?
 
It is your right to refuse to sign this authorization form.  If you do not sign this form, you will not be
able to participate in the research study.  Your health care outside the study will not be affected.  The
payment for your health care and your health care benefits will not be affected.
If you sign this authorization form, you will have the right to withdraw it at any time except to the
extent that the persons and organizations listed above:
have already taken action based upon your authorization;
need the previously collected information to complete analysis and reports of data for this
research; or
will continue to use and disclose previously collected information as permitted by the informed
consent form signed by you (except as to HIV-related information, for which disclosure to new
persons or organizations will not occur unless permitted by federal or state law). 
If you withdraw the authorization, you will not be permitted to continue taking part in the research
study.  This authorization form will not expire unless you withdraw it.  If you want to withdraw this
authorization, please write to the above named investigators. 
You have a right to see and copy your health information described in this authorization form in
accordance with The Rockefeller University's policies; in certain circumstances where the integrity of
the study will be affected, you will not be able to obtain your health records in this study until the
study has been completed.
You will receive a copy of this form after you have signed it.
 
 
Notice Concerning HIV-Related Information
If you are authorizing the release of HIV-related information, you should be aware that such
information may not be shared without your approval unless permitted by federal or state law.  You
also have a right to request a list of people who may receive or use your HIV-related information
without authorization.  If you experience discrimination because of the release or disclosure of HIV-
related information, you may contact the New York State Division of Human Rights at (212) 480-
2493 or the New York City Commission of Human Rights at (212) 306-7450.  These agencies are
responsible for protecting your rights.
 
Your signature
I have read this form, and all of my questions have been answered.  By signing below, I acknowledge
that I have read and accept all of the information above.
 

 
 
                                                           
Signature of participant or participant's legal
representative
 
                                                           
Printed name of participant
 
 
 
 
                                                           
Date
 
 
________________________________
Printed name of legal representative (if applicable)
 
 
                                    ___________
Representative's relationship to participant
 
 
 
 
 
 
THE STUDY PARTICIPANT OR HIS OR HER PERSONAL REPRESENTATIVE MUST BE PROVIDED WITH A
COPY OF THIS FORM AFTER IT HAS BEEN SIGNED.
 
38.0
End of Application Form
38.1   The study application form is complete.   
The next step in the submission  process is to gather attachments before proceeding to the
submission form. 
 
The following submission reports are generated in the Lab/Dept Reports menu, Submission
Reports section:
   - Delegation of Authority (if applicable, and if not previously generated)
   - HIPAA form (if applicable)
   - CCTS Utilization Report (required for all submissions)
   - Study Progress Report  (if the study has been managed in iRIS for a minimum of one
year, generate the Progress Report from the report menu in iRIS.  if the study has not been
managed in iRIS for one year, complete the Progress Report located on the IRB website.)
 
All other required forms can be downloaded from the corresponding sections' help links above or from
the IRB website.