# Maximizing germinal centers and somatic hypermutation to HIV Env immunogens

> **NIH NIH R37** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2021 · $922,142

## Abstract

Abstract
We propose that the features of germinal center 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. We have demonstrated that slow delivery
immunization changes fundamental aspects of the immune response, which can result in dramatic
improvements in nAb responses (Cell 2019). Conventional immunization strategies will likely be insufficient for
the development of a bnAb vaccine to HIV or other difficult pathogens due to the immunological hurdles posed,
including B cell immunodominance and GC quantity and quality. We found that two independent methods of
slow delivery immunization of RMs resulted in more robust Tfh cells and more GC B cells with Env-binding,
tracked by longitudinal lymph node (LN) fine needle aspirates (FNA) 1. Improved GCs correlated with the
development of > 20-fold higher titers of autologous tier 2 neutralizing Abs (nAbs). BCR sequencing and Ab
mapping demonstrated targeting of immunodominant non-neutralizing (nnAb) epitopes by conventional bolus
immunized animals, while slow delivery immunized animals targeted a more diverse set of epitopes, including
multiple tier 2 nAb epitopes. We will continue these groundbreaking studies to use novel slow release
technologies 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:** 10083078
- **Project number:** 2R37AI125068-06
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Shane P Crotty
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $922,142
- **Award type:** 2
- **Project period:** 2016-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10083078

## Citation

> US National Institutes of Health, RePORTER application 10083078, Maximizing germinal centers and somatic hypermutation to HIV Env immunogens (2R37AI125068-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10083078. Licensed CC0.

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