# Role of Vaccine-Induced Tissue-Resident Memory CD8+ T Cells in Protection Against Vaginal HSV-2 Infection

> **NIH NIH F31** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $41,008

## Abstract

PROJECT SUMMARY
Herpes simplex virus 2 (HSV-2) is a mucosally-transmitted infection for which there is no effective vaccine.
Human studies of latent HSV-2 infection strongly suggest that resident-memory CD8+ T cells (CD8 TRM) may
protect against viral reactivation, but it remains unclear whether CD8 TRM have the capacity to provide
sterilizing mucosal immunity against primary infection. Here, I propose to use a novel mouse model of vaccine-
induced vaginal CD8 TRM to investigate whether a solely CD8+ T cell-based response can protect against
vaginal HSV-2 challenge. In this model, mice are immunized with Listeria monocytogenes engineered to
express an immunodominant HSV-derived T cell epitope (LM-gB). Preliminary investigations revealed that
mice immunized with LM-gB generated a population of HSV-specific CD8 TRM that remained detectable in the
vagina for at least five months after vaccination. However, while circulating memory cells remained stable in
this model, vaginal CD8 TRM underwent a tenfold decay in the months following immunization. Mice with fewer
vaginal CD8 TRM responded poorly to HSV-2 challenge, exhibiting delayed T cell expansion and failure to
achieve protective immunity. By contrast, mice challenged earlier after immunization, when baseline numbers
of vaginal CD8 TRM were substantially higher, responded rapidly to infection and exhibited superior protection
against severe disease. Therefore, I propose to use this model of waning vaginal-resident immunity to
elucidate the relationship between CD8 TRM number and response kinetics after HSV-2 challenge, and
establish whether CD8 TRM induced by parenteral vaccination can mediate protective immunity. Finally, I will
determine whether mucosal LM-gB immunization enhances CD8 TRM lodgement and protective function.
Together, the aims of this proposal will clarify the role of mucosal CD8 TRM in genital HSV-2 infection, and shed
light on how to leverage the protective function of this memory population against HSV-2 and other sexually-
transmitted viral pathogens.

## Key facts

- **NIH application ID:** 9843433
- **Project number:** 5F31AI140514-02
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Veronica Anjali Dave
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $41,008
- **Award type:** 5
- **Project period:** 2018-12-11 → 2020-12-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843433

## Citation

> US National Institutes of Health, RePORTER application 9843433, Role of Vaccine-Induced Tissue-Resident Memory CD8+ T Cells in Protection Against Vaginal HSV-2 Infection (5F31AI140514-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9843433. Licensed CC0.

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