# Early Life Vaccination to Prevent HIV acquisition during Adolescence

> **NIH NIH P01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $1,375,878

## Abstract

ABSTRACT – Overall
Nearly 600,000 new HIV infections occur yearly in adolescents/young adults (ages 15-24 years), the only
population in which HIV infections continue to rise. The end of the HIV/AIDS epidemic will be achievable only
when an effective vaccine regimen can elicit long-term protective immunity in preadolescence, prior to sexual
debut. Yet, even the most promising HIV envelope (Env) vaccine platforms have failed to induce highly-
protective immunity in adults in preclinical and clinical studies. Interestingly, recent studies indicate that
durable, polyfunctional, and broad neutralizing antibody (bnAb) responses following HIV infection occur more
frequently and are equal or more potent in infants compared to that of adults. Yet, there remains a gap in our
understanding of the immunologic mechanisms associated with the rapid induction of HIV bnAb and effector
antibody functions within the infant immune landscape.
The overall goal of this HIVRAD renewal is to harness the unique qualities of the early life immune system for
vaccine elicitation of protective HIV immunity. This work builds on our current HIVRAD Program focusing on
the development of HIV Env vaccine regimens for prevention of infant HIV acquisition. We defined the optimal
vaccine intervals, adjuvants, and doses to achieve maximal immunogenicity in the infant immune system, and
determined that concurrent passive bnAb-active HIV Env immunization does not impair vaccine-elicited
immune responses. In this renewal HIVRAD Program, we hypothesize that HIV Env vaccine platforms
administered in early life and boosted in preadolescence will achieve more durable, broad, and polyfunctional
immune responses and be more efficacious at prevention of sexual transmission than initiation of immunization
in preadolescence. We will compare vaccine responses to two of the most promising HIV Env vaccine
candidates, bnAb germline-targeting SOSIP trimers (Project 1) and lipid nanoparticle mRNA vaccines (Project
2) initiated in infancy with boosting throughout childhood to that of initiation of vaccination in preadolescence in
the rhesus model (Nonhuman Primate (NHP) Core), and test their efficacy against intrarectal homologous
and heterologous SHIV challenge in adolescence. We will apply systems immunology to define the
immunologic, transcriptomic, and microbiologic signatures associated with the HIV Env vaccine antibody
function and induction of bnAb precursors (Integrated Systems Immunology Core (ISIC)). The
Administrative Core provides the full range of support for scientific, fiscal, and other programmatic
management and oversight. By leveraging the extended window for maturation of vaccine-induced responses
and defining the mechanistic advantages of early life immunization for effective anti-HIV responses, this
Program will inform the target population and design of an HIV Env vaccine that will provide life-long
protection.

## Key facts

- **NIH application ID:** 10379073
- **Project number:** 5P01AI117915-08
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Kristina De Paris
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,375,878
- **Award type:** 5
- **Project period:** 2015-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10379073

## Citation

> US National Institutes of Health, RePORTER application 10379073, Early Life Vaccination to Prevent HIV acquisition during Adolescence (5P01AI117915-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10379073. Licensed CC0.

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