# Investigation into the activation of multiple bnAb precursors using structure-designed immunogens and Ig knock-in mice

> **NIH NIH R01** · WISTAR INSTITUTE · 2024 · $910,966

## Abstract

Project Summary
HIV-1 vaccines that can elicit broadly neutralizing antibodies (bnAbs) are a primary goal. To date, it has been
demonstrated that a single bnAb lineage (VRC01-class) can be specifically activated in human trials. Antibodies
from this trial do not neutralize HIV-1 and heterologous sequential immunization is thought to be required to
develop bnAbs. Heterologous sequential immunization has been employed to generate bnAbs in pre-clinical
models. While VRC01-class antibodies isolated from infected individuals can be quite broad, the limit of breadth
for VRC01-class antibodies induced by these types of vaccination strategies in people is unknown. Therefore,
we are developing an alternative bnAb lineage targeting vaccine (VH1-46 class) through advanced protein
engineering approaches and assessment in newly generated human immunoglobulin knock-in mice harboring
VH1-46 germline antibodies. Further, we are pursuing innovative approaches to develop a dual bnAb lineage
targeting vaccine which could synergize with current VRC01-class vaccines. Individual lineage targeting
vaccines may not succeed at fully maturating these lineages, thus severely limiting the neutralization breadth
and ultimate effectiveness of these vaccines. Dual lineage targeting may be critical for success of the first bnAb-
eliciting HIV-1 vaccine.

## Key facts

- **NIH application ID:** 10734070
- **Project number:** 5R01AI172627-02
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Daniel Kulp
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $910,966
- **Award type:** 5
- **Project period:** 2022-11-03 → 2027-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10734070

## Citation

> US National Institutes of Health, RePORTER application 10734070, Investigation into the activation of multiple bnAb precursors using structure-designed immunogens and Ig knock-in mice (5R01AI172627-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10734070. Licensed CC0.

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