Abstract
Neisseria gonorrhoeae imposes a substantial global health burden due to its high incidence and escalating multidrug resistance. This study investigated the immunogenicity and efficacy of a peptide-based vaccine and a monoclonal antibody (mAb) targeting the conserved Loop2 epitope of the outer membrane protein MtrE. Two multiple antigenic peptide (MAP) vaccines, displaying four copies of MtrE Loop2 with or without a Cathepsin S cleavage site, were formulated with CpG1826 adjuvant. Immunization of mice elicited robust Loop2-specific IgM-dominant antibody responses with complement-dependent anti-gonococcal serum bactericidal activity. In a murine vaginal tract infection model, both vaccines demonstrated significant prophylactic and single-dose therapeutic efficacy. Furthermore, a human-mouse chimeric mAb (M01), consisting of mouse variable domains and human IgG1 constant domains, was generated from a dominant B-cell clonotype obtained from MAP vaccine-immunized mice. M01 exhibited high-affinity binding to MtrE and potent complement-dependent bactericidal activity. In a murine infection model, intravaginal administration of M01 significantly enhanced gonococcal clearance. Furthermore, Fc-engineered M01 variants confirmed that this efficacy was critically dependent on complement activity. These findings identify MtrE Loop2 as a promising target for both active and passive immunization strategies against N. gonorrhoeae, and underscore the critical role of complement-mediated activity as a mechanistic correlate of protection.
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Data availability
All data generated or analysed during this study are included in this published article. The original datasets generated and analysed during this study are available from the Zenodo repository at https://doi.org/10.5281/zenodo.18129123.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China [grant numbers 82572622, 82272382, 82150610507, 82072320]; and the Zhejiang Province Natural Science Foundation [grant number LZ24H190001]. The funder had no role in study design, data collection and interpretation, writing of the manuscript, or the decision to submit the manuscript for publication. We thank Lin Zhaoxiaonan and Xiao Guifeng from the Core Facilities of Zhejiang University School of Medicine for assistance.
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S.S. and H.G. are joined-first author. S.V. conceived the project. S.S. and S.V. designed the experiments. S.S., H.G., D.Y., X.G., W.L., C.D., Y.Q., and S.G. performed the experiments. S.S., X.L., H.C,. and S.V. analyzed the data. S.S. and S.V. wrote the manuscript. X.L. and H.C. edited the manuscript. All authors approved the final manuscript.
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S.V., S.S., H.G., D.Y., W.L., C.D., and Y.Q. are named inventors on a pending Chinese patent application (Application number: 2025115678059) covering intellectual property for mAb M01. X.G., S.G., X.L., and H.C. declare no competing interests.
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Song, S., Ge, H., Yuan, D. et al. MtrE Loop2-specific multiple antigenic peptide vaccine and monoclonal antibody confer complement-dependent protection against Neisseria gonorrhoeae. npj Vaccines (2026). https://doi.org/10.1038/s41541-026-01412-0
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DOI: https://doi.org/10.1038/s41541-026-01412-0
