# Project 2: RNA vaccination in early life to induce potent and broad HIV Env-specific antibody responses

> **NIH NIH P01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $714,185

## Abstract

ABSTRACT – Project 2
Globally, about 600,000 young adults (15-24 years of age) became infected with HIV-1 in 2017. Young women
age 15-19 years are most affected, and HIV-infection in this age group continue to rise. Therefore, a vaccine to
prevent HIV acquisition in young adults remains a top priority and needs to be effective prior to sexual debut.
The induction of broadly neutralizing antibodies (bnAbs) represents a major goal in HIV vaccine design. Yet, so
far, preclinical vaccine trials have only yielded modest results in eliciting bnAbs. Thus, novel vaccine strategies
are needed. Here, we propose to employ an HIV Env mRNA vaccine and to start vaccination in early life to
allow for the necessary time to develop bnAbs. Our rationale is based on data that bnAbs in HIV-infected
infants develop earlier and at higher frequencies compared to HIV-infected adults. Furthermore, bnAbs in HIV-
infected infants exhibit lower somatic hypermutation and, in contrast to adults, are more frequently directed
against multiple epitopes. These findings suggest that the infant immune landscape might be better equipped
for the development of bnAbs. Indeed, infants have higher frequencies of follicular T helper (TFH) cells that are
critical in driving germinal center B cell responses. Our mRNA vaccines will be packaged in lipid nanoparticles
(LNPs) that exert potent adjuvant activity for TFH and allow for sustained antigen release; both criteria have
been associated with neutralization breadth. Our preliminary data confirm that a nucleoside-modified HIV Env
gp160 mRNA-LNPs can induce potent TFH and GC responses and promote the induction of tier 1 and tier 2
nAbs in adult rhesus macaques (RMs). Based on this premise, we hypothesize that an HIV Env gp160
mRNA-LNP vaccine administered in early life allows for the time to mature vaccine-induced antibody
responses with broadly neutralizing and/or Fc-mediated effector functions that can be boosted in childhood,
and that protection against HIV acquisition in adolescence is superior to that achieved by vaccination in
preadolescence. We will test this hypothesis by comparing the immunogenicity of the same HIV vaccine given
either to infant or to preadolescent RMs and determine the protective efficacy against intrarectal SHIV
acquisition in adolescence (Aim 1). By applying several systems biology approaches and bioinformatic
pipelines, we will identify the developmental pathways resulting in bnAb responses. We will use system
immunology approaches to characterize the molecular and microbial signatures that accompany effective
vaccination within each of the age groups, further refining the vaccine strategies, including adjuvant design
(Aims 2 and 3). To enhance the translational potential of our NHP studies, we will perform an analysis of
Hepatitis B vaccine-induced B cell responses in rhesus and human infants in parallel. These data are expected
to inform the optimal age, intervals, number of boosts, and immune cell and micro...

## Key facts

- **NIH application ID:** 10147857
- **Project number:** 7P01AI117915-07
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Genevieve Giny Fouda Amou ou
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $714,185
- **Award type:** 7
- **Project period:** 2015-04-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147857

## Citation

> US National Institutes of Health, RePORTER application 10147857, Project 2: RNA vaccination in early life to induce potent and broad HIV Env-specific antibody responses (7P01AI117915-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10147857. Licensed CC0.

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