HBV Vaccination of Healthy Volunteers to Evaluate the Composition of Germinal Centers

NCT05272735 | Terminated Phase 4 FDA Drug

• 1 other identifier: GVI 1028
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Antibodies are the primary mediators of the protection against infection provided by vaccination. Antibodies become most powerful after the B cells that produce them undergo an evolutionary process called affinity maturation, in which antibodies increase their ability to bind to their targets, and thus neutralize pathogens. Affinity maturation occurs in structures within secondary lymphoid organs (for example lymph nodes or tonsils) known as germinal centers. Germinal centers are well known to be triggered by the first dose of vaccines, generating affinity matured plasma cells (B cells that secrete antibody into serum) and memory B cells, which can be converted into plasma cells by booster doses of vaccine. However, it is not fully understood the extent to which memory B cells can return to germinal centers again upon vaccine boosting. Such return would be very important to allow B cells, for example, to adapt to emerging variants of viruses such as influenza or SARS-CoV-2. This study will involve acquiring samples of B cells from germinal centers that form in response to vaccination with the highly effective hepatitis B vaccine. These cells will be analyzed to determine what fraction of them are memory B cells that returned to germinal centers upon boosting, information that is key to knowledge of how vaccine boosters work. Understanding the "rules" that govern how and when memory B cells choose to return to germinal centers in an effective vaccine such hepatitis B could help efforts to develop effective vaccination against more challenging, rapidly mutating viruses, such as influenza, HIV, and hepatitis C.

Conditions

Hepatitis B

Outcome Measures

Primary Outcomes (1)

• The Effects of HBV Vaccine on Memory B Cells

  The percentage of B cells in GCs triggered by the third dose of HBV vaccine that can derive from memory B cells.

  6 months

Secondary Outcomes (1)

• B Cell Response to the HBV Vaccination

  6 months

Study Arms (1)

Hepatitis B Vaccine (Recombinant)

EXPERIMENTAL

Hepatitis B Vaccine (Recombinant) 20 mcg intramuscular injection at 0-1-6 months

Biological: Hepatitis B Vaccine (Recombinant)

Interventions

Hepatitis B Vaccine (Recombinant) BIOLOGICAL

Hepatitis B Vaccine (Recombinant) 20 mcg intramuscular injection at 0-1-6 months

Hepatitis B Vaccine (Recombinant)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females
• Age 18-50 years Note: The HBV vaccine dose will be adjusted according to the Package Insert for participants who are 18 and 19 years of age.
• No prior history of HBV infection or vaccination.

You may not qualify if:

• HBV seropositivity (e.g. HBsAb, HBcAb or HBeAb)
• HIV infection
• Chronic HCV infection
• Pregnancy or lactation
• History of allergic reaction to any components of the HBV vaccine
• History of significant local or systemic reactogenicity to vaccines (eg, anaphylaxis, respiratory difficulties, angioedema, injection site necrosis or ulceration)
• Any clinically relevant abnormality on history or examination, including history of immunodeficiency or autoimmune disease; use of systemic corticosteroids (the use of topical or inhaled steroids is permitted), immunosuppressive, anticancer, antituberculosis or other medications considered significant by the Investigator within the previous 6 months; Note: The following exceptions are permitted and will not exclude study participation: use of corticosteroid nasal spray for rhinitis, topical corticosteroids for an acute uncomplicated dermatitis; or a short course (duration of 10 days or less, or a single injection) of corticosteroid for a non-chronic condition (based on Investigator clinical judgment) at least 2 weeks prior to enrollment in this study
• Any clinically significant acute or chronic medical condition that is considered progressive or in the opinion of the Investigator makes the volunteer unsuitable for participation in the study
• Bleeding disorder that was diagnosed by a physician (eg, factor deficiency, coagulopathy or platelet disorder that requires special precautions)
• Laboratory abnormalities:
• Platelets \<125,000 cells/mm3 PT/INR \>1.3 PTT \> 2 x ULN
• Receipt of live attenuated or mRNA vaccine within the previous 30 days or planned receipt within 30 days after IP administration; or receipt of other vaccine within the previous 14 days or planned receipt within 14 days after IP administration
• Participation in another clinical trial of an investigational product currently, within the previous 3 months or expected participation during this study

Sponsors & Collaborators

• Rockefeller University: lead
• Weill Medical College of Cornell University: collaborator

Study Sites (1)

The Rockefeller University

New York, New York, 10065, United States

Location

Related Publications (1)

• Mesin L, Schiepers A, Ersching J, Barbulescu A, Cavazzoni CB, Angelini A, Okada T, Kurosaki T, Victora GD. Restricted Clonality and Limited Germinal Center Reentry Characterize Memory B Cell Reactivation by Boosting. Cell. 2020 Jan 9;180(1):92-106.e11. doi: 10.1016/j.cell.2019.11.032. Epub 2019 Dec 19.

  PMID: 31866068 BACKGROUND

MeSH Terms

Conditions

Hepatitis B

Interventions

Hepatitis B Vaccines

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Gabriel D. Victora, PhD

  The Rockefeller University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2022
• First Posted: March 9, 2022
• Study Start: December 10, 2022
• Primary Completion: September 29, 2025
• Study Completion: September 29, 2025
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)