# Role of antibodies in vertical transmission of HIV-1

> **NIH NIH F30** · UNIVERSITY OF WASHINGTON · 2020 · $28,873

## Abstract

PROJECT SUMMARY/ABSTRACT
An effective HIV-1 vaccine will likely require the elicitation of humoral immunity in vaccine recipients.
Vaccination studies have shown proof-of-concept that pre-existing antibodies may have the potential to prevent
infection or slow disease progression upon HIV-1 or SIV exposure. Mother-to-child transmission (MTCT) is a
natural setting in which the characteristics of protective pre-existing antibodies can be studied. HIV-positive
mothers passively transfer HIV-specific IgG to their infants in utero, and these antibodies remain in infant
circulation for 6 months or more, a key period of breastfeeding exposure to HIV-1. Less than half of infants
born to HIV-positive mothers acquire HIV-1 through MTCT whereas the majority remain uninfected, even
without antiretroviral therapy. This proposal addresses the hypothesis that pre-existing passively-transferred
maternal antibodies present in infant circulation protect the infant from MTCT of HIV-1. Specifically, this
proposal focuses on the hypothesis that antibodies from non-transmitting mothers target specific epitopes that
confer their infants with protection from MTCT of HIV-1. It was recently reported that passively-transferred
antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC; a mechanism of killing infected cells)
was associated with reduced risk of infant mortality among infected infants and with a trend toward protection
from MTCT of HIV-1. This study used a unique cohort of samples from the Nairobi Breastfeeding Clinical Trial
(NBT) in Kenya, which was conducted from 1992-1998 before antiretroviral therapy was the standard of care.
Because pre-existing passively-transferred antibodies have been shown to play a role in infant outcomes in
this cohort, this cohort is ideal for in-depth investigation of the characteristics of beneficial passively-transferred
antibodies. In the first part of this proposal, antibody binding to a panel of HIV-1 antigens will be measured, and
epitopes of antibodies from non-transmitting and transmitting mother-infant pairs will be compared to determine
whether targeting certain epitopes is associated with reduced risk of MTCT. Because ADCC was shown to be
associated with improved infant outcome, the second part of this proposal will investigate the epitopes of these
ADCC-mediating antibodies. A competition assay will be used to test whether ADCC-mediating antibodies from
non-transmitting mother-infant pairs target different known ADCC epitopes compared to transmitting pairs. The
last part of this proposal will finely map epitopes of monoclonal ADCC-mediating antibodies isolated from
singly-sorted B cells from a non-transmitting mother who had high viral load, and thus was at high risk for
transmitting HIV-1 to her infant. The goal of finely mapping epitopes of ADCC-mediating antibodies from a high
risk non-transmitting mother is to characterize protective ADCC-mediating antibodies in detail. Overall, these
studies will shed...

## Key facts

- **NIH application ID:** 9851811
- **Project number:** 5F30AI136636-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Nicole Elise Naiman
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $28,873
- **Award type:** 5
- **Project period:** 2018-02-01 → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851811

## Citation

> US National Institutes of Health, RePORTER application 9851811, Role of antibodies in vertical transmission of HIV-1 (5F30AI136636-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851811. Licensed CC0.

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