# Nanodisc-displayed Protein Vaccines

> **NIH NIH U19** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2020 · $252,429

## Abstract

ABSTRACT
Neisseria gonorrhoeae (Ng) is a human-specific pathogen and the etiological agent of gonorrhea, a sexually
transmitted infection with a significant global health burden of ~78 million new cases annually. While often
asymptomatic, untreated gonorrhea can lead to pelvic inflammatory disease, ectopic pregnancy, infertility, and
increased transmission/acquisition of HIV. Because of the inexorable increase in antibiotic resistance, a
protective gonorrhea vaccine may be the only way to control disease transmission in the future. The recent
successes of the MenZB and 4CMenB outer membrane vesicle vaccines for Group B N. meningitidis (Nm)
provides a strong premise for development of an effective gonorrhea vaccine. Retrospective data suggested that
the MenZB vaccine was 31% effective against gonorrhea in the immunized cohort. In support of this finding, we
have shown that immunization with the similar 4CMenB vaccine markedly increased Ng clearance in the mouse
model of gonorrhea, and sera from 4CMenB-vaccinated mice cross-reacted with MtrE, BamA, and PilQ from Ng
outer membranes. Based on these data and the surface exposure, omnipresence, sequence conservation, and
importance in vital cellular functions of MtrE, BamA, and PilQ, we hypothesize that antibodies directed at the
extracellular regions of these antigens will provide protection against gonorrhea. Accordingly, the overarching
goal of this collaborative translational project is to develop a gonorrhea vaccine(s) by targeting MtrE, BamA, and
PilQ. Subunit antigens are proven candidates for vaccine development due to their safety, cost-effectiveness,
and rapid preparation. To develop effective gonorrhea vaccine(s), we propose an innovative approach of
incorporating the aforementioned antigens into nanoparticle platforms called nanodiscs (NDs) and combining
with different adjuvants in our vaccine formulations. NDs will enable antigen multivalency and native shape that
are important determinants of vaccine potency and efficacy, while adjuvants will be used to amplify robust
antigen-specific responses. For Project 3 of the Gonorrhea Vaccine Cooperative Research Center (GV CRC),
we will: i) purify full-length and/or the β-barrel regions of MtrE, BamA, and PilQ and natively display the proteins
in NDs (Specific Aim 1); ii) protein-NDs will be combined with different adjuvant compositions to induce robust
and balanced Th1/Th2 responses, and the resulting sera will be assessed for immunoglobulin subtypes, serum
bactericidal and opsonophagocytolytic activity, and binding to intact Ng (Specific Aim 2); and iii) test the most
promising antigen-ND/adjuvant combinations in the lower and upper reproductive tract mouse models of Ng
infection, as well as in a mixed Ng/Chlamydia muridarum infection model, for their capacity to decrease the time
of infection (Specific Aim 3). The success of the GV CRC will be greatly enhanced by the Outer Membrane
Vesicles and Proteomics Core (Core B), Host Response Monitorin...

## Key facts

- **NIH application ID:** 9900728
- **Project number:** 5U19AI144180-02
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** Aleksandra Elzbieta Sikora
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $252,429
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900728

## Citation

> US National Institutes of Health, RePORTER application 9900728, Nanodisc-displayed Protein Vaccines (5U19AI144180-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9900728. Licensed CC0.

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