# Neutralizing and non-neutralizing antibody effector functions in HIV infected children

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $707,803

## Abstract

Abstract
In 2016, it was estimated that 610,000 young people between the ages of 15 to 24 years were newly infected
with HIV. Preventing adolescent HIV infections will likely require the administration of a vaccine in childhood in
order to achieve protective immunity prior to sexual debut. Because of differences in the adult and early life
immune systems, understanding the development of HIV-specific antibody responses in children is critical to
guide the implementation of an HIV vaccine in pediatric populations. Previous studies investigating HIV
functional antibodies in children were limited in size, but their results suggested potential important differences
between adults and children. It was notably reported that 1) children may develop neutralization breadth earlier
than adults; 2) plasma neutralization breadth in children may be mediated by polyclonal antibodies in contrast
to adults in which one or two antibody specificities are responsible for breadth; and 3) infant broadly
neutralizing antibodies (bnAbs) may have lower levels of somatic hypermutation as compared to adult bnAbs.
Because the small sample size of these previous studies limits the generalization of their findings, we have
obtained a large panel of samples of ART naïve HIV-infected children from completed pediatric cohort studies
to investigate the development of HIV-specific antibody responses in early life. Preliminary experiments using
these specimens indicated that overall, 1 to 3-year-old children have significantly more neutralization breadth
than adults, suggesting that it could be easier to induce broad neutralization in children than in adults.
Importantly, elicitation of broad neutralization in children through vaccination will require the existence of a pool
of B cells with the potential to develop bnAbs (bnAb precursors). Yet, while recent studies have demonstrated
that bnAb precursors can be detected at low frequency in healthy adults, the frequency of bnAb precursors in
children is currently unknown. The overall goal of this study is to assess the development of HIV-specific
antibody responses in young children. Our primary focus in on bnAb responses, but because 1) Recent studies
have indicated that Fc effector functions are predictors of neutralization breadth in adults and 2) non-
neutralizing responses have be associated with protection in preclinical studies and might have contributed to
the partial protection observed in the RV144 vaccine trial; we will also measure non-neutralizing functional
antibody responses. We hypothesize that the early life immune landscape presents advantages for elicitation
of protective HIV-specific antibodies over the adult immune system. Our specific aims are: 1) To quantify and
characterize HIV neutralization breadth in a large cohort of HIV-infected children; 2): To assess the association
between polyfunctional Ab responses and neutralization breadth development in HIV infected children; and
finally 3) To quantify the freque...

## Key facts

- **NIH application ID:** 10104437
- **Project number:** 5R01AI143370-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Genevieve Giny Fouda Amou ou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $707,803
- **Award type:** 5
- **Project period:** 2019-03-07 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104437

## Citation

> US National Institutes of Health, RePORTER application 10104437, Neutralizing and non-neutralizing antibody effector functions in HIV infected children (5R01AI143370-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10104437. Licensed CC0.

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