# Maximizing germinal centers and somatic hypermutation to HIV Env immunogens

> **NIH NIH R01** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2020 · $841,574

## Abstract

   
DESCRIPTION (provided by applicant): Follicular helper T cells (Tfh) are the specialized CD4 T cells for B cell help and are limiting for GCs. We propose that the features of GC biology important for developing high affinity B cells to a very difficult epitope, such as a Tier 2 nAb epitope on HIV Env trimer, are very different than the well characterized features of GC biology for conventional antigens, such as haptens or even HIV gp120 V3 loop (a non-Tier 2 neutralizing epitope) for which a very small number of mutations (1-5 aa) suffice for maturation of high affinity B cells. Major limitations in our understanding of the biology of GCs to difficult
antigens include (1) "Is sustained exposure to antigen in GCs necessary for the extensive somatic hypermutation (SHM) associated with the generation of bnAbs?" and (2) "How much sequence space is explored by GCs in response to protein immunization, and how does that compare with the SHM seen in HIV Tier 2 neutralizing Abs?" We will use novel slow release technologies as tools to probe the biology of germinal centers relevant to affinity maturation against a difficult HIV trimer immunogen in non-human primates (NHP, rhesus macaques).

## Key facts

- **NIH application ID:** 9859324
- **Project number:** 5R01AI125068-05
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Shane P Crotty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $841,574
- **Award type:** 5
- **Project period:** 2016-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859324

## Citation

> US National Institutes of Health, RePORTER application 9859324, Maximizing germinal centers and somatic hypermutation to HIV Env immunogens (5R01AI125068-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9859324. Licensed CC0.

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