Development of a vaccine against gonorrhoea is a global priority, driven by the rise in antibiotic resistance and the need to protect against infection and reproductive health consequences. Although Neisseria gonorrhoeae (Ng) infection does not induce substantial protective immunity, there is evidence that highly exposed individuals may develop immunity against re-infection with the same strain. In contrast, retrospective epidemiological studies have shown that immunisation with vaccines containing Neisseria meningitidis (Nm) outer membrane vesicles (OMVs) provides a degree of cross-protection against Ng infection. To examine this phenomenon, we conducted a clinical trial of 4CMenB (Bexsero®, GSK), a licensed vaccine against Nm that contains OMVs and recombinant antigens, with 50 adults in coastal Kenya who have high exposure to Ng. The study comprised a single arm open label study of two doses of Bexsero; humoral and cellular immune responses were measured at three time points over six months. Using a dedicated microarray of Ng antigens, we show that serum IgG and IgA reactivities against the gonococcal homologs of the recombinant antigens in the vaccine peaked at 10 weeks but had declined by 24 weeks. The reverse was the case for most antigens originating from the OMV component. A cohort of similar individuals with laboratory-confirmed gonococcal infection were compared before, during, and after infection: their reactivities were weaker and differed from the vaccinated cohort. We conclude that the cross-protection of the 4CMenB vaccine against gonorrhoea could be explained by cross-reaction against a diverse selection of antigens derived from the OMV component.
Overall design
A panel of recombinant gonococcal proteins were printed in 5 replicates on a non-commercial protein microarray. Selected proteins from the proteome of the gonococcal strain FA1090 included transmembrane beta-barrel outer membrane proteins and proteins of non-cytoplasmic origin containing a signal peptide at their N-termini. FA1090 gonococcal strain lacks the expression of outer membrane lactoferrin-binding proteins A and B, so these antigens were included in the final selection based on the amino acid sequence of gonococcal strains NG104 and NG102, respectively. Additionally, major outer membrane porin proteins (PorB) from seven different alleles were also included in the final antigen selection. All proteins were expressed in E. coli as His-tagged proteins. Proteins with transmembrane sections were purified from inclusion bodies and the rest were purified from cytoplasmic fraction as soluble forms. Human IgG (at 11 different concentration points) was distributed in each array copy as control. Sera were profiled for anti-human IgG and anti-human IgA-specific analysis of reactivity to the spotted proteins.
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