# Neutralization Fingerprinting Analysis of Polyclonal Antibody Responses against HIV-1

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $610,412

## Abstract

Project Summary
HIV-1 poses a substantial health and economic burden, with more than 30 million people currently infected
worldwide. The search for an effective HIV-1 vaccine remains a top priority, and a deeper understanding of
how the immune system recognizes HIV-1 can help inform vaccine design. Lately, much effort has focused on
understanding the antibody responses to HIV-1 infection. However, the polyclonal neutralizing antibody
responses in an individual are very complex. Standard methods for mapping such responses include various
experimental techniques, but more recently, computational methods were also developed. These
computational methods, which we call NFP (neutralization fingerprinting), are based on analysis of serum
neutralization data that is typically obtained in the very first stages of donor sample characterization, and are
therefore an efficient technology for accurately mapping antibody specificities in polyclonal responses. The
NFP algorithms have already become an important tool in the HIV field and are being used extensively by
laboratories throughout the world, including Duke CHAVI-ID, CAPRISA, NIH VRC, and MHRP.
 Here, we propose to develop next-generation NFP algorithms and apply them to address biological
questions with important implications for understanding the interactions between HIV-neutralizing antibodies
and the virus. Specifically, we will develop and apply novel algorithms for: (1) Antibody specificity prediction
with significantly improved accuracy and reliability. These algorithms will immensely improve the utility of
the NFP approach for prospective identification of antibody specificities in polyclonal sera. (2) Mapping
broadly neutralizing antibody responses against novel epitopes on HIV-1 Env. We will use epitope-
structural analysis and computational search algorithms to identify novel Env epitopes, and will screen donor
samples for the presence of related NFP signals. Promising signals for novel antibody specificities will be
characterized further through collaborations. (3) Population-level analysis of broadly neutralizing antibody
responses to HIV-1. We will analyze large collections of samples from diverse HIV infection cohorts in order
to determine common antibody specificities elicited in response to HIV-1, as well as patterns of potential
association between features of the infecting virus sequence and the elicited epitope specificities.
 The proposed NFP algorithms will be made available to the public, and will be useful in a number of
high-impact areas in the HIV field, including mapping of antibody specificities in previously uncharacterized
samples, identification of novel Env epitopes, and large-scale analysis of broadly neutralizing antibody
responses within a cohort, or at a population level. Overall, this work will lead to a better understanding of the
neutralizing antibody responses against HIV-1 and will build a more complete picture of the epitopes on Env.
The proposed algorithmic fra...

## Key facts

- **NIH application ID:** 10151580
- **Project number:** 5R01AI131722-05
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Ivelin Georgiev
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $610,412
- **Award type:** 5
- **Project period:** 2017-06-06 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151580

## Citation

> US National Institutes of Health, RePORTER application 10151580, Neutralization Fingerprinting Analysis of Polyclonal Antibody Responses against HIV-1 (5R01AI131722-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10151580. Licensed CC0.

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