# Molecular signatures of broad neutralization in HIV infected children

> **NIH NIH R21** · DUKE UNIVERSITY · 2020 · $201,250

## Abstract

Abstract
The burden of HIV among adolescents and young adults remains high with more than 30% of new HIV
infections globally occurring among youth ages 15 to 24 years, making this a critical target population for
prevention strategies. While induction of broadly neutralizing antibodies (bnAbs), is a major goal for an HIV
vaccine, none of the candidate vaccines tested to date has been able to generate this sort of response.
Remarkably, recent studies have indicated that HIV infected children develop broad neutralization earlier
and more frequently than adults. To confirm these findings, we recently compared neutralizing antibody
responses in a large cross-sectional cohort of HIV infected children aged 1-3 years old to that of chronically
infected adults. By one year of age, the neutralization breadth in children was comparable to that of adults,
confirming that HIV infected children are able to develop broad neutralization early. Interestingly, contrary
to adults in which neutralization breadth is usually mediated by bnAbs of one or two specificities, in the
majority of children, neutralization appeared to be mediated by a polyclonal response. This suggests that
different mechanisms could drive the development of neutralization breadth in children and adults.
Importantly, a recent transcriptome analysis revealed an association between the expression of a protein
that regulates natural killer (NK) cell function (RAB11FIP5) and bnAb development in HIV-infected adults.
Early life NK cells are functionally different from adults NK cells; and it is well established that the early life
immune milieu is distinct from that of adults. Yet, whether the distinct early life immune environment or the
expression of specific factors such as RAB11FIP5 are associated with early broad neutralization
development in young children remains unknown. In this study, we therefore propose to test the hypothesis
that a distinct host transcriptional profile is associated with the development of HIV-specific antibody
neutralization breadth in early life, using archived, longitudinal samples from HIV-infected children enrolled
in the Mother and Infant cohort study (MICS) and the NICHD International Site Development Initiative
Pediatric study (NISDI). Our specific aims are: 1) To define the kinetics of development of broad
neutralization in a longitudinal cohort of HIV-infected children; and 2) To evaluate the association between
transcriptional profile and development of neutralization breadth in HIV-infected children. This study will
enhance our current understanding on the kinetics of neutralization breadth development in HIV-infected
children and provide novel insights on the molecular pathways leading to neutralization breadth
development early in life. Altogether, this new information will guide the development of HIV vaccine
strategies designed to protect prior to sexual debut. In addition, transcriptional signatures of broad
neutralization could serve as markers for the...

## Key facts

- **NIH application ID:** 10049204
- **Project number:** 1R21HD102851-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Genevieve Giny Fouda Amou ou
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,250
- **Award type:** 1
- **Project period:** 2020-05-06 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049204

## Citation

> US National Institutes of Health, RePORTER application 10049204, Molecular signatures of broad neutralization in HIV infected children (1R21HD102851-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10049204. Licensed CC0.

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