# Development of soluble and membrane bound immunogens to shepherd HIV-1 MPER specific BCR maturation

> **NIH NIH F31** · SCRIPPS RESEARCH INSTITUTE, THE · 2024 · $35,974

## Abstract

Project Summary/Abstract.
A small fraction of individuals infected with HIV-1 generate antibodies that can potently neutralize
diverse circulating strains of HIV-1. Such broadly neutralizing antibodies (bnAbs) have provided
sterilizing immunity in passive immunization studies in animal models. Therefore, the induction of
such antibodies by vaccination is a global health priority as a means to prevent HIV infection. The
membrane proximal external region (MPER) of the HIV-1 envelope protein (Env) is a site of
particular interest. A promising strategy to initiate bnAb induction is germline targeting (GT) in
which immunogens are engineered to specifically activate B cell precursors of bnAbs. Previous
work generated germline-targeting priming MPER epitope scaffolds capable of activating and
expanding 10E8-like precursor B cell receptors (BCRs) in mouse and non-human primate (NHP)
models. This project seeks to develop soluble and membrane-bound boost immunogens that
present the MPER epitope in a more native-like context with the aim of maturing primed BCRs to
acquire bnAb features.
Known bnAbs have high degrees of somatic hypermutation (SHM); therefore, I hypothesize that
vaccine induction of bnAbs will require sequential immunization with multiple immunogens
designed to shepherd affinity maturation of the BCR to acquire neutralization breadth and
potency. I will test this hypothesis through three primary aims to: 1) determine effect of mRNA vs.
protein immunogen delivery on immunogenicity and BCR maturation of 10E8-GT priming
candidates; 2) develop and test epitope-scaffold boost candidates for the ability to engage and
mature B cells activated by GT primes; 3) generate stabilized transmembrane envelope
constructs that preferentially bind MPER targeting antibodies. I expect the results of these aims
will generate candidate immunogens that bind with high affinity to 10E8-like antibodies with
various levels of mutation and maturity in order to shepherd antibodies towards breadth.
During this process, I will receive training in immunology, structural biology, and immunology from
my interdisciplinary mentors. The resources available at Scripps Research and from other
collaborators will ensure I develop the skills needed for my long-term goal of leading a vaccine
development research group.

## Key facts

- **NIH application ID:** 10924714
- **Project number:** 1F31AI179426-01A1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Olivia Swanson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $35,974
- **Award type:** 1
- **Project period:** 2024-08-02 → 2027-08-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10924714

## Citation

> US National Institutes of Health, RePORTER application 10924714, Development of soluble and membrane bound immunogens to shepherd HIV-1 MPER specific BCR maturation (1F31AI179426-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10924714. Licensed CC0.

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