# Role of local antibodies in control of chronic genital herpes

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2024 · $887,376

## Abstract

PROJECT SUMMARY/ABSTRACT
Infection with Herpes simplex virus 2 (HSV-2) for which there is no vaccine is a significant cause of human
morbidity both in the United States and worldwide. Current understanding of humoral immunity to HSV-2 is based
on bulk metrics of antibodies circulating in bloodstream, however everyday battle between virus and host occurs
in microscopic tissue microenvironment which represent a unique immunological niche. Our premise is that study
of local humoral responses will reveal critical, currently unidentified mediators and mechanisms for immune
control of HSV-2. After primary infection, HSV-2 establishes latency in sensory neurons. Clearance and
subsequent control of constantly reactivating HSV-2 in tissue are believed to depend on T cells, but clinical
observations and mathematical models present evidence consistent with essential role for local humoral
responses required to achieve efficient virus control, Our preliminary data has shown that antibody secreting
cells (ASCs) are actively present in genital skin during HSV-2 reactivation and long after virus outbreak is
contained. Using the power of having sequential samples in individual tissue biopsies over time combined with
recent advancements in single-cell RNA sequencing we demonstrated that these clonally expanded cells commit
to the long-lived plasma cell lineage implying possible tissue residency, Isolation of antibodies from these unique
cells has shown they recognize HSV-2 suggesting they may be directed to as yet unidentified HSV-2 antigens
and/or provide functions important for virus control in the tissue. Therefore, the goal of this project is to thoroughly
define the immunoprotective role of skin antibody-secreting cells (ASCs) against reactivating HSV-2. Underlying
our proposed experiments is the idea that tissue resident ASCs have the ability to contain the virus over long
timeframes via secreting HSV-2 specific antibodies that are essential for virus control due to their specificity
and/or effector functions. Therefore, we focus on critical features of ASCs such as antigenic specificity, gene
expression profile, clonal structure and functional activity of cognate antibodies during symptomatic HSV-2
reactivation and at multiple time points following clearance of a genital skin virus within microscopic sites of
infection. We will also evaluate frequency of essential clones of skin ASCs among circulating B cells that have
direct implication for rational vaccine design allowing targeted vaccination strategies. Ultimately, our goal is to
use the gained insights to develop strategies that will allow for novel approaches to design successful herpes
vaccine and development of immunotherapeutic approaches to treat chronic HSV-2 infection.

## Key facts

- **NIH application ID:** 10883435
- **Project number:** 1R01AI178284-01A1
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Anton M Sholukh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $887,376
- **Award type:** 1
- **Project period:** 2024-02-05 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883435

## Citation

> US National Institutes of Health, RePORTER application 10883435, Role of local antibodies in control of chronic genital herpes (1R01AI178284-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10883435. Licensed CC0.

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