Evaluation of Immunization Route in Induction of Vaccine-Mediated Anti-Gonococcal Immune Responses in a Murine Model of Ascending Infection

Abstract

Background: Identification of immune correlates in murine gonorrhea models has been hampered by study-dependent differences in vaccine antigens and administration routes. We previously showed that detergent-detoxified outer membrane vesicles (dOMVs) isolated from a PorA-, PorB-, and RmpM-deficient meningococcal strain (ΔABR) elicit antibodies that cross-react with Neisseria gonorrhoeae and enhance gonococcal clearance in a mouse model of lower reproductive tract infection. In this study, we investigated whether (1) ΔABR dOMVs can protect mice from ascending gonococcal infection and (2) vaccination route influences immune responses.

Methods: Mice were vaccinated subcutaneously (SC) or intraperitoneally (IP) and then vaginally inoculated with gonococci. Bioburden of mice was measured and assessed relative to ΔABR dOMV-induced cellular and humoral immune responses.

Results: Subcutaneous and intraperitoneal vaccination accelerated gonococcal clearance from the lower and upper reproductive tract at similar rates. Probing of gonococcal protein microarrays with immune sera from the 2 groups identified multiple vaccine targets that were commonly immunogenic. Despite comparable clearance patterns in vaccinated mice, differences in immune induction were observed that were dependent on administration route. SC immunized mice demonstrated a neutrophil influx that correlated with decreased vaginal bioburden; higher serum bactericidal activity against nonsialylated gonococci was also noted. In contrast, IP immunization induced higher serum and vaginal IgA levels, serum bactericidal activity against sialylated gonococci, and antigonococcal opsonophagocytic killing activity of neutrophils.

Conclusions: This work demonstrates that ΔABR dOMVs protect against ascending gonococcal infection and that cellular and functional antibody responses to the same candidate vaccine may vary depending on immunization route.

Keywords: Neisseria gonorrhoeae; ascending infection; gonorrhea; outer membrane vesicles (OMVs); vaccine.