# Outer membrane vesicle vaccine against gonococcal and meningcoccal disease

> **NIH NIH R21** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $209,375

## Abstract

Gonorrhea is the second most common bacterial sexually transmitted infection – the most common is
chlamydia, which often coinfects with gonorrhea. About 80 million new cases of gonorrhea occur worldwide
annually. Over 555,000 cases were reported in the U.S. in 2017. Serious sequelae of gonorrhea in women
include infertility, ectopic pregnancy and chronic pelvic pain. Neisseria gonorrhoeae (Ng), the causative agent
of gonorrhea, has become resistant to almost every antibiotic in clinical use. Resistance to ceftriaxone and
azithromycin – the recommended first-line of treatment – portends an era of untreatable gonorrhea. The CDC
has listed Ng as a microorganism with a threat level of “Urgent.” Development of a safe and effective vaccine
against gonorrhea is a public health priority. Our group has shown that a monoclonal antibody (mAb) called
2C7 that targets a widely-expressed Ng lipooligosaccharide (LOS) epitope (the 2C7 epitope) is bactericidal. A
peptide mimic (mimitope) of the 2C7 epitope, when configured as a polymer (a ‘multiantigen peptide’) elicits
bactericidal Abs and attenuates Ng vaginal colonization in mice. Encouraged by the recent retrospective
observation that a group B meningococcal vaccine composed of detergent-extracted outer membrane vesicles
(MeNZB) designed to curtail a meningococcal epidemic in New Zealand also reduced incident gonococcal
disease by 31%, we will incorporate the gonococcal 2C7 epitope into meningococcal outer membrane vesicles
to target both meningococci and gonococci. This innovative approach is advantageous because both diseases
are highly prevalent in adolescents and young adults. In addition to the economic advantages, a ‘pan-
Neisseria’ vaccine would help address an already crowded vaccination schedule and may mitigate the stigma
associated with vaccines against STIs. In Aim 1, we will develop meningococcal native outer membrane
vesicles (NOMVs) containing LOS that displays the 2C7 epitope. Meningococcal FH-binding protein (FHbp) will
be mutated to abrogate binding of human FH and thereby elicit higher bactericidal Ab against Nm than wild-
type FHbp. We will also delete Rmp and H.8, which may elicit blocking Ab against Ng and Nm, respectively.
Elicited Abs will be tested for complement-dependent bactericidal activity against homologous and
heterologous Ng strains and tested for efficacy versus Ng in transgenic mice we have developed that express
the human complement inhibitors, FH and C4BP, to better simulate the complement environment in humans.
We will use mice deficient in C9 (the last step in formation of the bacteriolytic pore) or mice depleted of PMNs
to elucidate the mechanism of action of the candidate vaccine, which will also define correlates of protection. In
Aim 2, we will develop detergent-extracted outer membrane vesicle vaccines (dOMVs) that display the 2C7
mimitope peptide in the framework of the major outer membrane protein, PorA. Immunogenicity and efficacy of
this vaccine will be evaluate...

## Key facts

- **NIH application ID:** 10115599
- **Project number:** 5R21AI146621-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Lisa Ann Lewis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $209,375
- **Award type:** 5
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115599

## Citation

> US National Institutes of Health, RePORTER application 10115599, Outer membrane vesicle vaccine against gonococcal and meningcoccal disease (5R21AI146621-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10115599. Licensed CC0.

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