Evaluation of Neisseria Gonorrhoeae Opacity (Opa) Protein Loops as Targets for Passive Vaccination and Investigation of the Role of Opa Proteins During Infection of a Female Host

Neisseria gonorrhoeae opacity (Opa) proteins mediate adherence and invasion of host cells, resistance to complement, and immunosuppression. Presented here are studies on the potential of conserved Opa protein loops as targets for passive vaccination and investigations into the role of Opa proteins during infection of the female genital tract. We demonstrated antibodies that target conserved Opa loops, the semi-variable (SV) and fourth loop (4L), recognized antigenically distinct Opa proteins. Antibodies to cyclic peptides that correspond to the SV loop (AbSV cyclic) recognized more Opa variants than antibodies generated against linear SV-loop peptides (AbSV linear). AbSV linear and AbSV cyclic, but not Ab4L linear, bound intact gonococci. AbSV cyclic, but not AbSV linear agglutinated bacteria and antibodies to a hypervariable loop 2 cyclic peptide (AbHV2BD cyclic) agglutinated and blocked interactions with cervical cells. AbHV2BD linear and AbHV2I linear were bactericidal, and this bactericidal activity was increased 8-fold when a nonhuman source of complement was used. Preincubation of Opa loop-specific antibodies with homologous variants did not protect mice from colonization; however protection studies were technically limited as 50% of the antibody was shed within one hour postadministration.