# Characterizing the broad antibody response to HIV superinfection

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2022 · $802,400

## Abstract

ABSTRACT:
Eliciting broad and potent HIV-specific neutralizing antibody (Nab) responses represents a holy grail of HIV
vaccine efforts. To date, our understanding of the potential of the human immune system to generate such
responses comes from the study of a subset of HIV-infected individuals who generate broad Nab responses as
a result of a dominant monoclonal response. In contrast to the singly infected individuals who have been the
topic of these previous studies, there is limited data on people who are superinfected with HIV and acquire two
distinct strains of the virus from different partners. We have shown that superinfected individuals have broad
Nab responses that cannot be explained by a monoclonal response to the known HIV epitopes. Our
preliminary detailed study of one individual suggests that superinfection leads to a polyclonal response that
results from distinct responses to the two infecting viral strains. We hypothesize that the complex dynamic
between viruses in superinfection may contribute to the unique polyclonal response. To address this
hypothesis, we propose to take advantage of our well-characterized cohort of superinfection, which represents
the largest collection of cases identified to date. Among these individuals, we have identified several with
broadly neutralizing antibody responses that do not map to a single known epitope target. We propose to
isolate monoclonal antibodies from these individuals and determine the basis for the breadth of their response
and whether the response is polyclonal. We will define the epitopes of the antibodies and the role that the initial
and superinfecting virus played in eliciting them. We will also determine the evolutionary process that led to
these responses. These studies represent a unique opportunity to understand how to elicit a polyclonal
response to HIV, which may present a higher barrier to escape and resistance than a monoclonal response.

## Key facts

- **NIH application ID:** 10327673
- **Project number:** 6R01AI138709-05
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** JULIE M. OVERBAUGH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $802,400
- **Award type:** 6
- **Project period:** 2018-02-07 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327673

## Citation

> US National Institutes of Health, RePORTER application 10327673, Characterizing the broad antibody response to HIV superinfection (6R01AI138709-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10327673. Licensed CC0.

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