# Optimizing Humoral Responses to HIV-1 Env Vaccine Antigens

> **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $885,499

## Abstract

Project Summary
BCR affinity drives selection of mutations that increase potency and breadth in serum antibody (Ab), but also
predisposes the fate choices of GC B cells towards terminal PC differentiation. We will study the role of BCR
affinity in determining the fates of B cells exposed to serial immunizations or chronic SHIV infection to optimize
vaccine efficacy. Parallel studies carried out in knock-in mice expressing the germline ancestor (UCA) of a V3
glycan bNAb lineage and in rhesus macaques (RMs) will merge lineage tracing of GC B and T cells with high
throughput transcriptional analysis of individual lymphocytes to determine how and what immunological
environments maximize the probability of eliciting broadly neutralizing antibody (bNAb) responses. We will use
engineered Env vaccine antigens (Ags) to optimize the return of Bmem to secondary and tertiary GCs in BCR
KI mice, and to determine how BCR affinity affects differentiation to the GC, Bmem and PC compartments. In
SHIV infected RMs, we will in parallel map BCR affinities associated with nascent bNAb production and
determine the effects of prior immunization with selected Env vaccines on subsequent, homologous or
heterologous infection.

## Key facts

- **NIH application ID:** 10808992
- **Project number:** 5P01AI131251-08
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** GARNETT H KELSOE
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $885,499
- **Award type:** 5
- **Project period:** 2017-03-07 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808992

## Citation

> US National Institutes of Health, RePORTER application 10808992, Optimizing Humoral Responses to HIV-1 Env Vaccine Antigens (5P01AI131251-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10808992. Licensed CC0.

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