Determining the role of inhibitory antibodies on complement-mediated killing of \(\textit{Neisseria gonorrhoeae}\) during acute gonorrhoea infection

McKeand, Samantha Anastasia ORCID: 0000-0001-5579-7422 (2023). Determining the role of inhibitory antibodies on complement-mediated killing of \(\textit{Neisseria gonorrhoeae}\) during acute gonorrhoea infection. University of Birmingham. Ph.D.

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Abstract

The mechanism of inhibitory antibodies produced by patients during acute gonorrhoea infection is largely unknown, and thus far there has been a lack of large-scale studies of the human immune response to the gonococcus to elucidate this mechanism. During this study, 336 clinical \(\textit{Neisseria gonorrhoeae}\) isolates were screened for resistance against their autologous participant serum. Serum bactericidal assays revealed serum samples from nine participants which contained inhibitory antibodies. These isolates were sensitive to healthy serum, but resistant when incubated with the autologous participant serum. Antibody isotypes IgG, IgM and IgA were purified from inhibitory serum. After serum bactericidal assays with the autologous purified antibodies, it was observed that all isolates tested were protected from killing by healthy serum by purified inhibitory IgG and IgM at the highest concentrations trialled. IgA was able to inhibit killing in half of the isolates trialled. Closer analysis of the IgG subclasses involved in inhibition, showed a correlation between increased binding of IgG2 and a decreased binding of IgG3 to isolates demonstrating the inhibitory phenotype. This mechanism is distinct from previous literature on inhibitory antibodies against other Gram-negative organisms. Further analysis of the mechanism would be invaluable for informing gonococcal vaccine development.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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