# Dissecting Polyclonal Sera to Reveal Correlates of Productive Immune Responses to HIV

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2023 · $870,554

## Abstract

Project Summary/Abstract
Rational, structure-based immunogen design for HIV vaccine development has began 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 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 analyzing shepherding or polishing immunization
strategies that are now being attempted for HIV vaccine development, wherein immunogens are
designed to elicit and mature antibodies with specific features in CDRs that resemble known broadly
neutralizing antibodies (bnAbs). In this renewal application we propose to extend the resolution,
throughput, and utility of our EMPEM approach. Moreover, since most pathogens will enter the body
through mucosal surfaces, analysis of (vaccine-induced) mucosal antibodies will be explored. The data
generated will provide new correlates of productive immune responses to the portfolio of exciting HIV
immunogens with epitope focusing or germline targeting properties that will help down select and
prioritize amongst the various approaches being pursued.

## Key facts

- **NIH application ID:** 10716061
- **Project number:** 2R01AI136621-06
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Lars Oliver Hangartner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $870,554
- **Award type:** 2
- **Project period:** 2018-03-16 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10716061

## Citation

> US National Institutes of Health, RePORTER application 10716061, Dissecting Polyclonal Sera to Reveal Correlates of Productive Immune Responses to HIV (2R01AI136621-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10716061. Licensed CC0.

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