# Scientific Core: Structural Proteomics

> **NIH NIH P01** · SCRIPPS RESEARCH INSTITUTE, THE · 2024 · $181,565

## Abstract

Project Summary/Abstract
Rational, structure-based immunogen design for HIV vaccine development has begun to deliver promising
results in both, pre-clinical non-human primate (NHP) and clinical studies such as the IAVI G001 phase I trial
[NCT03547245]. Moreover, advances in single cell RNAseq and electron microscopy-based polyclonal antibody
mapping (EMPEM) have enabled analysis of both vaccine and pathogen-induced antibody responses at
unprecedented resolution, further enabling rational vaccine design. EMPEM and single cell B cell analysis deliver
fundamentally different data formats that if properly integrated, can illuminate immune responses at
unprecedented detail. We recently extended the original negative stain EMPEM method, capable of
distinguishing polyclonal antibody epitope specificities and angle of approach, to high resolution cryoEM-based
EMPEM to yield molecular details of epitope-paratope interfaces. In the best cases we can derive some
sequence information for the complementarity determining regions (CDRs) from structural data, identify Vh/Vl
gene usage, and query databases of antibody BCR sequences to directly generate monoclonal antibodies. As
such, we can short cut the laborious efforts to generate epitope specific monoclonal antibodies using
conventional methods. These molecular details are critical for identifying how bona fide human germline bnAb
precursors engage germline targeting immunogens such as the V2 apex targeting Q23 immunogen. EMPEM is
also critical for evaluating polyclonal antibody responses in BCR knock-in mice that have been immunized with
germline targeting immunogens that are designed to prime and mature antibodies with specific features in CDRs
that resemble known broadly neutralizing antibodies (bnAbs). The Structural Proteomics Core will be highly
integrated into all both Project 1 and 2 as well as the Animals and Data Cores within this P01 application,
providing unique structural data to evaluate, refine, and optimize multi-epitope germline targeting immunogens
for development as candidate HIV vaccines.

## Key facts

- **NIH application ID:** 10852995
- **Project number:** 5P01AI177683-02
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Andrew Barrett Ward
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $181,565
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10852995

## Citation

> US National Institutes of Health, RePORTER application 10852995, Scientific Core: Structural Proteomics (5P01AI177683-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10852995. Licensed CC0.

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