# Novel vaccine antigens against N. gonorrhoeae

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 2022 · $580,195

## Abstract

Neisseria gonorrhoeae is the causative agent of the sexually transmitted infection (STI) gonorrhea, a disease
with high morbidity worldwide, estimated at 87 million cases annually, and severe reproductive tract
complications in women. Current treatment approaches against gonorrhea are compromised by recent onset of
antibiotic resistance. There is a pressing need for an effective vaccine against N. gonorrhoeae, but protective
antigens have been limited, so far. Our previous work on the gonococcal transcriptome during human natural
infection has described differences in mRNA expression of gonococcal genes in urethral and vaginal lavage
samples fromnaturally-infected subjects as compared to mRNA expression when the correspondinggonococcal
strains were cultured in vitro. We termed those genes “in vivo-expressed factors” (IVEFs). We also reported that
~30% of the gonococcal genes expressed during infection are hypothetical proteins. We hypothesized that
gonococcal hypothetical proteins expressed and regulated during infection include new candidate antigens for a
vaccine against N. gonorrhoeae. Through a bioinformatics-based candidate antigen selection strategy (CASS)
that examined predicted immunogenicity, cellular localization, conservation in N. gonorrhoeae and structure
features of the gonococcal hypothetical proteins, we identified 36 new potential targets (ongoing R21AI131004).
We investigated an initial group of 6 antigens, confirming 3 as surface-exposed proteins (NGO0690, NGO0948
and NGO1701) that induced cross-reactive antibodies with complement-mediated serum bactericidal activity
(SBA) against diverse N. gonorrhoeae strains. In preliminary studies, a combination of these antigens showed
promise as protective vaccine candidates in a mouse model of gonococcal infection. Correlates of protection
against gonorrhea in humans are not known but SBA and reduced vaginal colonization in mice are stepping-
stones in preclinical gonococcal vaccine evaluation. An example is the (currently most advanced) N.
gonorrhoeae vaccine candidate, the 2C7 LOS epitope (and its mimotope TCMP2). Other cited mechanisms of
protection include antibody-dependent inhibition of bacterial adhesion or invasion of host cells at the colonization
site, but these have yet to be confirmed in human studies. The goal of this project is to validate and improve
the efficacy of our three candidates as gonococcal vaccine antigens. In Aim 1, we propose antigen dosing
and adjuvant studies to achieve optimal immune responses to our candidates and SBA; in Aim 2 we will validate
protection in the available female mouse model of gonococcal vaginal colonization, broaden strain coverage by
including TMCP2, and correlate immune effector mechanisms and protection; in Aim 3, we will define the
function of the hypothetical protein candidates and their impact on N. gonorrhoeae virulence, fitness and
Immunity, a necessary complement for their selection as vaccine candidates. Our studies will provide...

## Key facts

- **NIH application ID:** 10344080
- **Project number:** 1R01AI166537-01
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Paola Massari
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $580,195
- **Award type:** 1
- **Project period:** 2022-09-08 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10344080

## Citation

> US National Institutes of Health, RePORTER application 10344080, Novel vaccine antigens against N. gonorrhoeae (1R01AI166537-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10344080. Licensed CC0.

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