# Targeting Evasion Factors: Discovery of novel antibodies for durable suppression of HSV reactivation

> **NIH AI R21** · DARTMOUTH COLLEGE · 2026 · $215,758

## Abstract

ABSTRACT
 Chronically-reactivating HSV is an underserved disease. Beyond lesions suffered by affected
individuals, reactivation results in risk of transmission to others, especially as subclinical reactivation occurs
with high frequency. Further, the isolation of ACV resistant strains, the inability of long-term ACV treatment to
fully control reactivation, and the emerging evidence for HSV infection as a risk factor for neurodegeneration
provide strong rationale for development of novel therapies to reduce rates of reactivation.
 Promisingly, epidemiological and preclinical evidence supports the ability of antibodies to modify rates
of reactivation. However, because reactivation takes place in individuals with endogenous antibodies, there is
reason to believe that monoclonal antibodies (mAbs) with attributes distinct from those commonly induced by
natural infection will be needed to provide optimal benefit in this challenging clinical setting.
 To this end, diverse viral glycoproteins function to evade host defenses, and targeting these activities
could both interfere with viral pathogenesis and drive immune-mediated clearance. Glycoproteins E and I form
a complex (gE/gI) thought to function by binding to the IgG Fc domain and sweeping virus-specific Ab off the
surface of virions and infected cells for degradation. Glycoprotein C (gC) inhibits complement activation by
binding C3b. Both glycoproteins facilitate cell-to-cell spread. Blocking these host evasion and viral spreading
mechanisms through binding of mAb Fab domains at the same time as driving innate immune clearance
mechanisms through the effector functions of the Fc domain has the potential to turn these evasion
mechanisms from assets into vulnerabilities.
We hypothesize that mAbs targeting viral evasion factors gE/gI and gC will exhibit both direct and
indirect antiviral effects. They will inhibit the functions of these evasion factors and contribute to viral and
infected cell clearance through Fc-domain d

## Key facts

- **NIH application ID:** 11267570
- **Project number:** 1R21AI195395-01
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Margaret E Ackerman; David A Leib
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $215,758
- **Award type:** 1
- **Project period:** 2026-04-10T00:00:00 → 2028-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11267570

## Citation

> US National Institutes of Health, RePORTER application 11267570, Targeting Evasion Factors: Discovery of novel antibodies for durable suppression of HSV reactivation (1R21AI195395-01). Retrieved via AI Analytics 2026-07-13 from https://api.ai-analytics.org/grant/nih/11267570. Licensed CC0.

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