# Role of female genital mucosa associated CD4 T cells in vaccine-induced HIV susceptibility

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $196,250

## Abstract

Project Summary
Vaccine-triggered CD4 T cell help is essential for establishing long-lived humoral and cellular immunity and is
central to HIV vaccine efficacy. But, CD4 is also the major receptor for HIV which raises concerns as to
whether vaccine induced CD4 T cells could subvert vaccine efficacy; a premise supported by the STEP trial
and several HIV vaccine studies in non-human primates, including our own. The cellular mechanisms
underlying the paradox of vaccine-induced susceptibility to HIV remain poorly articulated, and yet
identifying the mechanism involved is the first step to effective vaccine design. This proposal is focused
on understanding CD4 T cells in the female genital tract (FGT), the major portal of HIV entry by heterosexual
transmission. In Aim 1 of this research project, we will investigate functional characteristics of highly
vulnerable HIV target CD4 T cells within the genital tract of HIV uninfected humans and rhesus macaques. In
Aim 2 of this proposal, we will investigate how a DNA-prime/protein boost vaccination regimen, a widely used
HIV vaccine platform, impacts the phenotype of FGT associated HIV target CD4 T cells. We will determine
whether vaccine-specific CD4 T cells in the FGT express key markers of HIV vulnerability and whether this is
driven by vaccine induced changes in the cytokine milieu. We will also determine how preventing migration of
vaccine-induced cells to the FGT impacts the vaginal inflammatory environment. Finally, we will elucidate
dynamics of vaccine-induced CD4 T cells in the FGT after simian (S)IV exposure and explore cells
disseminated to the rectal mucosa and lymphoid tissue. The chances of ameliorating the virus is greatest in the
earliest stages of infection, at the mucosal point of entry; thus, our findings could lay the foundation for
determining whether inhibiting the migration of HIV target cells to the FGT during the post-vaccination effector
phase is a strategy to decrease vaccine-induced susceptibility to HIV.

## Key facts

- **NIH application ID:** 9831610
- **Project number:** 5R21AI143454-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Swaminathan Smita Iyer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,250
- **Award type:** 5
- **Project period:** 2018-12-05 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9831610

## Citation

> US National Institutes of Health, RePORTER application 9831610, Role of female genital mucosa associated CD4 T cells in vaccine-induced HIV susceptibility (5R21AI143454-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9831610. Licensed CC0.

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