# Design of vaccination strategies to elicit broadly neutralizing antibodies against HIV-1

> **NIH NIH R00** · WISTAR INSTITUTE · 2022 · $249,000

## Abstract

PROJECT SUMMARY/ ABSTRACT
 AIDS is a preventable disease, nevertheless millions of new infections occur every year according to
UNAIDS. A vaccine that elicits broadly neutralizing antibodies (bNAbs) against HIV-1 would be the best way to
prevent the spreading of the AIDS pandemic, however, no efficacious vaccine has been developed to date.
Previous efforts to design an antibody-based vaccine have been unsuccessful, in part due to the limited
information available at the time on the HIV-1 particle, its mechanism of infection and the anti HIV-1 antibody
responses elicited in infected individuals. Recent advances in the field have opened new avenues for vaccine
design that we will investigate as part of the research of this proposal. Our work recently showed that common
vaccination strategies using singular Envelope (Env)-based immunogens were not suitable to elicit anti HIV-1
bNAbs; instead, novel sequential immunization strategies elicited neutralizing antibodies of remarkable
potency and breadth in knock-in mouse models with a restricted antibody repertoire. In this proposal, we aim
to design and evaluate new immunogens and sequential immunization strategies to elicit bNAbs in
animal models that have a complete immunoglobulin (Ig) repertoire. In particular we plan to: 1) test new
immunogens and sequential immunization regimens to elicit bNAbs against the V3-N332 epitope of Env in a)
wild type mice, b) AlivaMAb mice carrying human Ig loci and c) mice expressing the human terminal
deoxynucleotidyl transferase (Tdt) enzyme as models that more closely resemble the human Ig repertoire; and
2) document the requirement of glycans on the V3-N332 epitope at the early stages of V3-N332 bNAb
development. The results of the proposed research will provide valuable information for the design of a vaccine
against HIV-1. This work will also inform about general rules governing the antibody maturation process upon
sequential immunization that could facilitate the design of vaccines against other unrelated pathogens. The
K99 phase of this proposal will take place in the Nussenzweig laboratory at The Rockefeller University in
collaboration with the Bjorkman laboratory in Caltech. Both groups and institutions will offer an outstanding
environment and all necessary resources to carry out the research of this proposal. The Nussenzweig
laboratory has a long and consolidated trajectory studying B cells and HIV-1. The Bjorkman laboratory
specializes in structural biology and is particularly interested in the immune recognition of viral pathogens such
as HIV-1. The work of the Bjorkman group perfectly complements the areas of expertise of the Nussenzweig
laboratory and provides an optimal scenario for the research of this proposal. The training received during the
K99 phase in this terrific environment will undoubtedly propel and facilitate my transition to independence.

## Key facts

- **NIH application ID:** 10487555
- **Project number:** 5R00AI140770-04
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Amelia Escolano
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10487555

## Citation

> US National Institutes of Health, RePORTER application 10487555, Design of vaccination strategies to elicit broadly neutralizing antibodies against HIV-1 (5R00AI140770-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10487555. Licensed CC0.

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