# Supramolecular pediatric HIV vaccine design

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $777,485

## Abstract

Abstract
A pediatric vaccine against HIV would have a significant clinical impact, because more than 150,000 infants
are infected with HIV every year globally, despite the availability of antiretroviral drugs to prevent mother-to-
child transmission. In addition, a pediatric HIV vaccine that offers protection in infancy and durable protective
immunity prior to sexual debut would significantly reduce adolescent HIV infections. Developing a pediatric HIV
vaccine will require to overcome specific immunological challenges dues of limitations of the early life immune
system including 1) a reduced ability to provide T-cell help, which results in poor somatic hypermutation of
antibodies and inadequate antibody affinity, and 2) the need for several vaccine boosts to achieve durable
immunity. Paradoxically, recent studies have demonstrated that children can develop neutralization breadth
earlier than adults, suggesting that the early life immune system could be more amendable for the elicitation of
this highly desirable response through vaccination. A leading strategy for elicitation of broad neutralizing
antibody response is to immunize with native live HIV envelope trimers. Yet, despite advances in stabilization
and production of native-like HIV-1 envelope trimers over the last decade, typical vaccination strategies with
HIV-1 Envelope SOSIP trimer products have been disappointing in their ability to raise broad and potent virus-
neutralizing activity. Novel vaccine platforms may be needed to improve the immunogenicity of Envelope
SOSIP trimer vaccines. In this collaboration, we will develop an innovative nanofiber pediatric HIV vaccine
comprised of a scaffolded CH505 SOSIP Env trimer and a synthetic T-Cell epitope (PADRE) self-assembled
into supramolecular nanofibers. We hypothesize that the PADRE- nanofiber conjugated HIV-1 CH505 SOSIP
trimer vaccine (P-Q11 CH505 trimer) will enhance the magnitude and potency of tier 2 virus neutralization
responses in small animal and infant non-human primate (NHP) models, and will be protective against
homologous SHIV challenge in an infant NHP challenge model. Our specific aims are: 1) Develop and assess
the antigenicity the nanofiber-conjugated CH505 SOSIP trimer subunit vaccine; 2) Define the immunogenicity
of the P-Q11 CH505 trimer vaccine in neonatal rabbits and infant rhesus macaques in comparison to that of
CH505 SOSIP Env trimer alone (Go/No-Go endpoint); and 3) Determine the ability of the P-Q11 CH505 trimer
vaccine to protect against low dose oral SHIV challenge in an infant nonhuman primate model of late postnatal
transmission via breastfeeding. This novel pediatric HIV vaccine strategy could overcome the challenges of
infant vaccination, while taking advantage of the immunologic and practical benefits of early life immunization
for elicitation of protective immunity.

## Key facts

- **NIH application ID:** 9902327
- **Project number:** 5R01AI145016-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Joel H Collier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $777,485
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902327

## Citation

> US National Institutes of Health, RePORTER application 9902327, Supramolecular pediatric HIV vaccine design (5R01AI145016-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9902327. Licensed CC0.

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