# Pre-Clinical Development of a Intranasal Bivalent gD2/gB2 HSV-2 Mucosal Vaccine

> **NIH NIH R44** · BLUEWILLOW BIOLOGICS, INC. · 2021 · $994,743

## Abstract

ABSTRACT
Genital herpes simplex virus-2 (HSV-2) infections are a major public health problem affecting >40 million people
in the United States and >500 million globally. HSV-2 infection is characterized by painful recurring, genital
sores and this can coincide with considerable psychological distress. Transmission can occur during sexual
contact and from mother to child during birth with fatal consequences. Although several vaccines have been
shown to elicit strong neutralizing activity against the virus, there is currently no effective vaccine to prevent
HSV-2. Recent research has shown that while systemic, humoral immunity is beneficial, co-induction of mucosal
immunity is prerequisite for full protection. BlueWillow Biologics has established NanoVax®, a proprietary oil-in-
water nanoemulsion (NE01) adjuvant technology, that is designed for intranasal immunization. We've
demonstrated the ability of NE01 to augment the targeting of antigens to the immune system while safely eliciting
potent humoral, mucosal and cellular immune responses, including balanced induction of Th1, Th2 and Th17
cells. This feature facilitates the development of efficacious vaccines that induce mucosal and cell mediated
immunity for full protection against various respiratory and sexually transmitted pathogens, including HSV-2.
To address this unmet medical need, BlueWillow Biologics is developing a novel, intranasal bivalent vaccine
comprised of two HSV-2 glycoproteins (gB2 and gD2) formulated in NE01. Our preclinical studies have shown
that the resulting intranasal vaccine (IN) gB2/gD2-NE01 is an effective and commercially viable prophylactic
strategy to prevent HSV-2 infections. We have optimized the processes for scale-up manufacturing of the
antigens to achieve reproducible production of highly pure gB2 and gD2 drug substances at a scale sufficient to
meet clinical demand. Importantly, we've demonstrated the prophylactic equivalency of the drug substances
prepared from the established scale-up manufacturing processes to those we previously prepared at lab scale.
This demonstrates our ability to manufacture high quantity of pure material while preserving the integrity and
activities of the key vaccine components.
In this Phase IIB SBIR program, BlueWillow Biologics will execute the remaining development work on the IN
gB2/gD2-NE01 HSV-2 vaccine necessary to submit an investigational new drug (IND) application. Using the
established scale-up processes established under Phase II, we will refine the gB2 expression process to improve
yield, manufacture two batches of each antigen, along with the NE01 adjuvant, and dedicate the material
towards completing an IND-enabling GLP toxicology study and formulating clinical material for stability
assessment. The preparation of this material will enable a pre-IND meeting with the FDA to request feedback
and approval of our GLP toxicology study design. Upon completion of the GLP toxicology study, BlueWillow will
be ready to file an...

## Key facts

- **NIH application ID:** 10228074
- **Project number:** 5R44AI126964-04
- **Recipient organization:** BLUEWILLOW BIOLOGICS, INC.
- **Principal Investigator:** Vira Bitko
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $994,743
- **Award type:** 5
- **Project period:** 2017-03-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228074

## Citation

> US National Institutes of Health, RePORTER application 10228074, Pre-Clinical Development of a Intranasal Bivalent gD2/gB2 HSV-2 Mucosal Vaccine (5R44AI126964-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10228074. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*