An Open Label Study of IgG Fc Glycan Composition in Human Immunity

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.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Biological: IM Pneumococcal, meningococcal, or flu vaccine

Detailed Description

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 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. We will also study whether healthy adults who have been previously infected with dengue, zika or chikungunya virus generate distinct Fc glycoforms after vaccination compared with healthy adults who have not been previously infected with any of these viruses.

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • The Rockefeller University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or Female 18-80 years of age
• Healthy volunteers without significant medical problems
• Able to give informed consent to participate
• Willing to receive a single dose of an FDA-approved vaccine (either the influenza virus, pneumococcal or meningococcal vaccine)
• Documented previous infection with dengue, zika or chikungunya virus or no history of dengue, zika or chikungunya infection.

Exclusion Criteria:

• Prior allergic reaction to commercial vaccination
• For Flumist participants: Close contact with person with severely compromised immune system requiring isolation
• 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)
• History of seizure disorder for Flumist group participants only.
• Participation in another clinical study of an investigational product currently or within the past 90 days, or expected participation during this study.
• Any clinically significant acute or chronic medical condition requiring care of a physician (e.g., diabetes, coronary artery disease, rheumatologic illness, malignancy, substance abuse) that, in the opinion of the investigator, would preclude participation.
• In the opinion of the investigator, the volunteer is unlikely to comply with the study protocol.
• Currently taking systemic steroids or other immunomodulatory medications including anticancer medications and antiviral medications.
• Egg allergy
• Received the influenza vaccine less than 1 month ago and/or received the pneumococcal and meningococcal vaccine less than 4 years ago
• Confirmed HIV infection, positive for hepatitis B surface antigen or positive for hepatitis C antibodies.
• Is pregnant or lactating
• History of Guillain-Barre syndrome
• Poor venous access
• Unable to continue participation for 12 weeks
• Any clinically significant abnormality on medical history or physical examination including history of immunodeficiency or autoimmune disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Biologic/Vaccine, Age 18-64 cohort; Vaccination. IM Pneumococcal, meningococcal, or flu vaccine	Biological: IM Pneumococcal, meningococcal, or flu vaccine; Volunteers given one of the 3 vaccines; Other Names: FluMist, Pneunomovax, or Menveo vaccine
Active Comparator: Biologic/Vaccine, Age 65-80 cohort; Vaccination. IM Pneumococcal, meningococcal, or flu vaccine	Biological: IM Pneumococcal, meningococcal, or flu vaccine; Volunteers given one of the 3 vaccines; Other Names: FluMist, Pneunomovax, or Menveo vaccine
Active Comparator: Vaccine, healthy adults; Vaccination. IM Pneumococcal, meningococcal, or flu vaccine	Biological: IM Pneumococcal, meningococcal, or flu vaccine; Volunteers given one of the 3 vaccines; Other Names: FluMist, Pneunomovax, or Menveo vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percent (of 100%) of IgG With Galactosylation, Fucosylation and/or Sialylation	The percent of Fc glycans that are galactosylation, fucosylation and/or 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) or by mass spectrometric analysis. 100% of IgG were found to have these modifications.	One Day

Collaborators and Investigators

• Sponsor: Rockefeller University
• Investigators: Principal Investigator: Taia T Wang, MD PhD, Rockefeller Univesrity

Publications and helpful links

General Publications

• Maamary J, Wang TT, Tan GS, Palese P, Ravetch JV. Increasing the breadth and potency of response to the seasonal influenza virus vaccine by immune complex immunization. Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10172-10177. doi: 10.1073/pnas.1707950114. Epub 2017 Sep 5.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2013
• Primary Completion (Actual): March 1, 2023
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: October 17, 2013
• First Submitted That Met QC Criteria: October 17, 2013
• First Posted (Estimated): October 22, 2013

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: immune response
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: TWA-0804

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No