Systemic and Mucosal Antibody Responses Against Neisseria gonorrhoeae (Ng) Outer Membrane Vesicle Antigens following Four-Component Meningococcal Serogroup B (4CMenB) Immunization in Healthy Adults: A Randomized Phase II Trial.

Meningococcal serogroup B (MenB) vaccines containing outer membrane vesicles (OMVs) may provide cross-protection against Neisseria gonorrhoeae infections but vaccine-induced mucosal immune responses remain poorly characterized. This phase 2, double-blind, randomized, placebo-controlled trial evaluates the immunogenicity of four-component MenB vaccine (4CMenB) against OMVs from gonococcal strains 1291 and CNG20. Study outcomes were IgG antibody responses (assessed using ELISA) in rectal mucosal secretions (primary), serum (secondary), vaginal secretions and saliva (exploratory). Healthy adults aged 18-49 years, with no history of gonorrhea and low-risk for infection, were randomized 4:1 to receive 4CMenB (N = 41) or placebo (N = 11) on Days 1 and 29, with follow-up to Day 181. At baseline, serum IgG against both gonococcal OMVs is detectable in all participants, and mucosal IgG is present in many. 4CMenB elicits robust serum IgG responses to gonococcal OMVs, peaking at Day 43 and remaining elevated at Day 181. Mucosal responses are low-magnitude and exhibit different kinetics by site, with the highest responses in vaginal secretions, which peak at Day 43, followed by rectal secretions and saliva, which peak at Day 57. Responses are largely absent in placebo recipients. Two-dose 4CMenB induces systemic and mucosal IgG to N. gonorrhoeae, supporting its potential role in gonorrhea prevention. The trial registration number is NCT04722003.