NCT01967238

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

• Status: Terminated
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 129 (actual)
• Sponsor: Rockefeller University · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Accepted

Summary

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.

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.

Conditions

• Healthy

Interventions

Type	Name	Description
BIOLOGICAL	IM Pneumococcal, meningococcal, or flu vaccine	Volunteers given one of the 3 vaccines

Timeline

• Start date: 2013-03-01
• Primary completion: 2023-03-01
• Completion: 2023-03-01
• First posted: 2013-10-22
• Last updated: 2024-09-19
• Results posted: 2024-09-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study