# Developing Immunogens to Elicit Broadly Neutralizing anti-HIV-1 Antibodies

> **NIH NIH P01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2024 · $890,425

## Abstract

Project Summary
Despite AIDS being a preventable disease, UNAIDS reports millions of newly HIV-1 infected people every
year. An efficacious vaccine for HIV-1 is therefore highly sought after. Despite many efforts, attempts to create
immunization regimens that reproducibly elicit broadly neutralizing antibodies (bNAbs) against HIV-1 have
failed thus far. The field has focused on developing a sequential immunization strategies that through priming
with immunogens that activate germline bNAb precursor B cells, followed by boosts with increasingly more
native Env based-immunogens, shepherds these germline precursors through somatic hypermutation in the
germinal center to the develop into mature bNAbs-expessing cells. Whereas priming immunogens now exist
that can reliably activate the correct bNAb precursor B cells, the immune response over the course of
sequential immunization regimens becomes increasingly less focused on target epitopes and non-neutralizing
off-target responses start to dominate the antibody response over time. To aid the design of better boosting
immunogens by the Bjorkman and Hahn/Shaw labs, the Nussenzweig lab will conduct experiments in wt and
transgenic mice to identify better boosting immunogens and dissect mechanisms that lead to off-target epitope
responses in sequential immunization. Recent experiments from the Nussenzweig lab indicate that antibody
feedback and the quality and quantity of the T follicular helper cell response affect recruitment and affinity
maturation of germinal center (GC) B cell. Passively infused monoclonal antibodies in immunologically intact
mice and humans indicated that antibody feedback resulted in the emergence of more off-target responses by
masking target epitopes. Moreover, memory B cells emerging from such GCs are selected by a mechanism
favoring antibody repertoire diversity over affinity8,11. HIV-1 immunogens designed by the Bjorkman lab will be
used by the Nussenzweig lab to explore how polyclonal antibody responses alter the outcome of sequential
immunization with the aim to improve on-target responses during boosting. The concepts that will be
delineated from these experiments will then be tested in RM models by the Hahn/Shaw laboratories.

## Key facts

- **NIH application ID:** 10810307
- **Project number:** 2P01AI100148-11
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Pamela J Bjorkman
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $890,425
- **Award type:** 2
- **Project period:** 2013-02-10 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10810307

## Citation

> US National Institutes of Health, RePORTER application 10810307, Developing Immunogens to Elicit Broadly Neutralizing anti-HIV-1 Antibodies (2P01AI100148-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10810307. Licensed CC0.

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