# Demystifying the antiviral activity of the IgG3+ antibody response

> **NIH NIH R37** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $604,800

## Abstract

While the development of an HIV vaccine that can induce neutralizing antibodies (nAbs)
remains a top priority, nearly 3 decades of research in this arena has proven that this is a
daunting task. However, recent results from the modestly protective RV144 vaccine trial argue
that protection from infection can be achieved in the absence of nAbs and cytotoxic T cell
responses, and this protection and may be linked to the induction of functional antibodies (Abs)
that target specific epitopes on the viral V2 loop. Likewise, more than 3 decades of research
have pointed to a role for non-neutralizing, innate immune–recruiting Abs in antiviral control and
slower disease progression. Interestingly, over the last R01 funding period, it has become clear
that in both the setting of vaccine-induced immunity and natural infection, the most functional
antibody (Ab) responses are driven by HIV-specific IgG3 Abs. However, what these IgG3
antibodies target, how these IgG3 responses are induced, and most critically how they persist in
some patients has yet to be defined. Here, we hypothesize that the rules of long-lived IgG3
selection can be learned from both vaccination and natural infection, with the hope that
the induction of these potent humoral effector molecules prior to exposure to HIV may
lead to durable protection from infection. Therefore, in this application, we propose to
specifically dissect the specificity and functional profile of the HIV-specific IgG3 responses in
both infection and vaccination. Based on these results, we will isolate antigen-specific IgG3 B
cells to begin to learn the “rules” by which these B cells select a particular antibody subclass as
well as how these responses may be artificially skewed towards IgG3 with adjuvants, T cell
help, and/or cytokines. Together, these studies, linking antibody function to B cell programming
will provide a first-in-class composite picture of the evolution of protective functional Abs and
define the mechanisms by which protective immunity may be elicited through vaccination to gain
enhanced control over the virus.

## Key facts

- **NIH application ID:** 9740056
- **Project number:** 4R37AI080289-11
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Galit Alter
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $604,800
- **Award type:** 4C
- **Project period:** 2008-07-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9740056

## Citation

> US National Institutes of Health, RePORTER application 9740056, Demystifying the antiviral activity of the IgG3+ antibody response (4R37AI080289-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9740056. Licensed CC0.

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