Investigation of correlates of protection against gonococcal infection by comparative immunoprofiling of responses in experimental and clinical studies.
basic_science · Level V
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- Record sourced from PubMed, PMID 42053374.
- Also identified by DOI 10.1093/infdis/jiag216.
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Abstract
Neisseria gonorrhoeae is an important cause of sexually transmitted infection with rising antimicrobial resistance. Epidemiological studies suggest that vaccines containing meningococcal outer membrane vesicles (OMVs), for example 4CMenB (Bexsero), offer partial cross-protection, but immune correlates of protection are unknown. We used a murine genital tract infection model to compare systemic and mucosal responses after immunization with Bexsero, gonococcal OMVs (Ng OMVs) with alum, or alum alone. Vaccinated mice were challenged intravaginally with N. gonorrhoeae. Serum bactericidal activity (SBA) was measured, and antigen-specific IgG responses were profiled using custom gonococcal protein microarrays. Murine responses were compared with those in high-risk humans immunized with Bexsero and patients with gonococcal infection. Bexsero vaccination significantly accelerated bacterial clearance compared with Ng OMV or alum controls. Serum and vaginal IgG profiles were highly correlated, revealing distinct antigenic signatures between vaccine groups. Bexsero elicited responses to some gonococcal orthologs of its recombinant antigens (GNA1030, GNA2091, NHBA), whereas Ng OMVs induced responses to Opa, PilQ, and MtrE. While SBA did not correlate with accelerated clearance, there was an association between PMN influx to the genital tract and reduced bacterial load. Comparative analyses demonstrated concordance between antigen-specific IgG patterns in sera and vaginal washes, and between Bexsero-immunized mice and human vaccinees. Protein microarrays combined with multivariate analysis identified antibody signatures associated with protection against gonococcal infection. Concordant patterns of murine and human IgG responses highlight the translational value of the mouse model for defining correlates of protection and guiding rational gonococcal vaccine development.