# Gonococcal peptide vaccine candidate display using HPV virus-like particles

> **NIH NIH R21** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $181,867

## Abstract

ABSTRACT
About 87 million new cases of gonorrhea occur globally, annually. In 2018, 583,405 cases were reported in the
U.S, an 82.6% increase in disease incidence since the historic low in 2009. Human papillomaviruses (HPVs)
are the causative agents of cervical cancer, the 4th most common cancer in women globally, resulting in
~567,000 cases and 311,000 deaths every year. About 80% of these cases occur in resource-poor developing
countries. There are currently three licensed effective prophylactic HPV vaccines. Despite the great success of
these vaccines, the cervical cancer burden remains high, particularly in developing countries, as these
vaccines are expensive and type-specific. Neisseria gonorrhoeae (Ng), the causative agent of gonorrhea, has
become resistant to almost every antibiotic in clinical use and portends an era of untreatable gonorrhea.
Development of a safe and effective vaccine against gonorrhea is a global public health priority.
Lipooligosaccharide (LOS) is the most abundant molecule on the gonococcal surface and plays multifaceted
roles in bacterial virulence. A LOS epitope recognized by mAb 2C7 (therefore called the 2C7 epitope) is
expressed by >95% of Ng in vivo; Ng mutants that do not express the 2C7 epitope are attenuated in mice. This
is because the 2C7 LOS epitope can be modified with sialic acid, which increases resistance of the bacteria to
complement-dependent killing and engages Siglec receptors to down-regulate host inflammation. We have
developed a peptide mimic (mimitope) of the 2C7 epitope, which when configured as a multi-antigen peptide
(MAP) elicits bactericidal Abs and attenuates Ng colonization in mice in a complement-dependent manner.
This project will leverage the HPV virus-like particle (VLP) platform to deliver the 2C7 mimitope. VLPs are an
excellent platform to enhance immunogenicity of peptides. We have already produced HPV VLPs that express
the Ng mimitope peptide (called HPV-Ng) in tobacco plants and in mammalian cells on a small scale.
Production in tobacco plant expression could reduce costs, an important consideration for vaccines against
STIs that disproportionately affect socio-economically underprivileged populations. In Aim 1 we will test the
immunogenicity and in vitro function of antibodies (Abs) elicited by HPV-Ng. We will measure Ab responses in
male and female BALB/c, C57BL/6 and CD1 mice against i) the 2C7 LOS epitope and ii) against HPV16. An
intact complement system is necessary and sufficient for activity in vivo of Ab against the 2C7epitope.
Therefore, we will test complement-dependent bactericidal activity of immune Ab against Ng. The ability of
anti-HPV Ab to neutralize pseudovirions (PsVs) – an in vitro measure of efficacy against HPV – will be
measured. In Aim 2, the efficacy of HPV-Ng against Ng will be tested in a gonococcal vaginal colonization
model in mice that express human complement inhibitors, to better simulate the complement system of
humans and provide a more stringen...

## Key facts

- **NIH application ID:** 10496571
- **Project number:** 5R21AI167283-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** SANJAY RAM
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $181,867
- **Award type:** 5
- **Project period:** 2021-09-27 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10496571

## Citation

> US National Institutes of Health, RePORTER application 10496571, Gonococcal peptide vaccine candidate display using HPV virus-like particles (5R21AI167283-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10496571. Licensed CC0.

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