# Targeting CD4 T follicular helper cells for enhancing HIV vaccine induced humoral immunity

> **NIH NIH R56** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $773,942

## Abstract

Project Summary
Anti-retroviral therapy (ART) has dramatically altered the HIV pandemic landscape by rendering the disease
manageable - but still incurable. Significant barriers are associated with the global implementation of ART that
limit its utility for sustainable prevention of HIV. Moreover, the intersection of aging-related conditions and the
consequences of long-term ART will have a substantial impact on the healthcare system as well as on HIV
patients. These challenges underscore the need to pursue strategies that will provide both sustainable HIV
prevention and a functional HIV cure. The results of the RV144 trial indicate that vaccination may prevent HIV
transmission in humans and that durability of anti-envelope (Env) HIV antibodies may be the key to this
protection. Efforts to improve upon the RV144 trial have demonstrated that booster immunizations increase
serum anti-Env antibody titers only transiently. This “anti-Env antibody persistence problem” impedes our
efforts to develop an effective HIV vaccine. This proposal is designed to improve our functional understanding
of the immunological mechanism involved in producing durable HIV Env antibodies in both the systemic
circulation and the rectal and vaginal mucosa. To accomplish this, we will be using a DNA-prime/Protein-boost
vaccine regimen in rhesus macaques. Aim 1 of this research project is focused on establishing how Th1 versus
Th1/Th17 priming impacts innate inflammatory response, Env TFH frequencies, phenotype, transcriptional profile,
and B cell helper capacity, as well as systemic and mucosal anti-Env antibody titers. Aim 2 will determine
whether combining the state-of-the-art soluble Env mimic, an Env SOSIP trimer protein immunogen with a highly
potent and robust adjuvant (to induce Th1/Th17 response, results in increased production of a high-quality, long-
lasting anti-Env antibodies relative to Th1 vaccine regimen. We will further investigate whether vaccine-mediated
induction of the polyfunctional TFH response improves protection when faced with a mucosal simian HIV
challenge. These preclinical studies will establish the mechanistic and experimental foundations to identify how
TFH helper cell profiles impact anti-Env antibody longevity and vaccine efficacy and will lay the necessary,
evidence-based foundation for the design of a successful HIV vaccine.

## Key facts

- **NIH application ID:** 10374194
- **Project number:** 1R56AI150409-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Swaminathan Smita Iyer
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $773,942
- **Award type:** 1
- **Project period:** 2021-05-12 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374194

## Citation

> US National Institutes of Health, RePORTER application 10374194, Targeting CD4 T follicular helper cells for enhancing HIV vaccine induced humoral immunity (1R56AI150409-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10374194. Licensed CC0.

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