# Immunogen design and testing

> **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $609,490

## Abstract

PROJECT SUMMARY
Project 3 will test the hypothesis that identification of the transmitted founder and mutated, sequential SHIV
Env glycoproteins that bind germline or evolved V1V2 or V3-glycan broadly-reactive neutralizing antibody
(bNAb)-specific B cell receptors (BCRs) will provide immunogens that will initiate similar bNAb lineages in
rhesus macaques (RM) in the setting of vaccination. Soluble native-like Env trimers, glycopeptides, and/or
DNA vectored env gp160 construct immunogens will be produced to determine the optimal immunogen forms
required for initiation and elicitation of V1V2- and V3-glycan targeted Nabs. In this project, sequential Env
immunization regimens will be designed in collaboration with Projects 1 and 2 and Cores B (Sequencing) and
C (Bioinformatics and Statistics). Protection following vaccination will be assessed using autologous and
heterologous SHIVs from Project 1.
Specific aims of Project 3 are:
1. To express autologous TF and evolved Envs from SHIV-infected RM as recombinant gp120s and
 as stabilized trimers;
2. To perform binding assays of bNAb lineage BCRs with evolved autologous and heterologous Envs
 and, in conjunction with the Bioinformatics and Statistics Core, to design sequential Env immunogens
 based on binding affinity and/or on mutations inferred bioinformatically to be associated with bnAbs
recognition;
3. To perform immunization studies of Env constructs in bNAb germline humanized mice and RM,
including:
 (a) B cell repertoire analysis and plasma neutralization assays on vaccinated mice
 and RMs in collaboration with Project 2,
 (b) sequential immunizations with adjuvants and checkpoint inhibitor
 administration to promote bNAb lineage survival and maturation, and
 (c) negative-stained EMs and vaccine-induced antibody-Env co-crystallization
 studies of vaccine-induced antibodies.
Project 3 will synergize with Projects 1 and 2 and Cores B and C to complete the pre-clinical translational
pipeline for developing HIV vaccine strategies based on recapitulating the virologic and immunologic events
that occur in bNAb development during transmitted/founder Env SHIV infection in RMs.

## Key facts

- **NIH application ID:** 9880391
- **Project number:** 5P01AI131251-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Barton F. Haynes
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $609,490
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880391

## Citation

> US National Institutes of Health, RePORTER application 9880391, Immunogen design and testing (5P01AI131251-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9880391. Licensed CC0.

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