# Project 1: Immunogen Design and Delivery

> **NIH AI P01** · SCRIPPS RESEARCH INSTITUTE, THE · 2026 · $570,516

## Abstract

PROJECT SUMMARY/ABSTRACT
The development of an effective HIV vaccine remains a major challenge. Previous strategies for HIV vaccine
design aimed to elicit protective T cell responses, non-neutralizing antibodies, broadly neutralizing antibodies
(bnAbs), or some combination of the three but have failed to protect against infection. There is a growing
consensus that critical elements to a successful bnAb-based vaccine will be its ability to: i) efficiently activate
and expand multiple rare naïve bnAb-encoding B cell precursors; ii) immunofocus these B cell responses to
canonical, conserved bnAb epitopes on the HIV Env trimer and away from off-target epitopes; and iii) affinity-
mature these response to breadth by heterologous vaccinations. The study design proposed in this application
addresses each of the critical aspects of bnAb elicitation. The grant aims to elicit bnAbs by a novel strategy that
combines priming of HIV bnAb encoding rare B cell precursors by rationally designed germline-targeting trimer
immunogens and expand their breadth with diverse heterologous trimer boosts. The project 1 includes three
aims: Aim #1 will develop an HIV trimer immunogen that can target rare V2-apex and V3-glycan bnAb-encoding
precursor B cells. Using in-vitro directed reverse vaccine engineering platform, we will develop germline-targeting
priming immunogen that exhibits enhanced affinity for V2 apex and V3-glycan bnAb UCAs to utilize as a priming
immunogen to active rare bnAb B cell precursors to these sites. Aim #2 will investigate the priming efficiency of
GT-trimer immunogen delivered through various vaccine platforms, to in vivo activate V2-apex and V3-glycan
bnAb B cell precursors in various bnAb precursor expressing animal models. The aim is to generate a robust
epitope specific memory B cell response that could be further boosted toward breadth. Aim #3 will investigate
various boost strategies using newly designed diverse HIV trimers to expand the neutralization breadth 

## Key facts

- **NIH application ID:** 11312611
- **Project number:** 5P01AI177683-04
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Raiees Ahmad Andrabi
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $570,516
- **Award type:** 5
- **Project period:** 2023-06-01T00:00:00 → 2028-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11312611

## Citation

> US National Institutes of Health, RePORTER application 11312611, Project 1: Immunogen Design and Delivery (5P01AI177683-04). Retrieved via AI Analytics 2026-05-19 from https://api.ai-analytics.org/grant/nih/11312611. Licensed CC0.

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