A Recombinant Chlamydia trachomatis MOMP Vaccine Elicits Cross-serogroup Protection in Mice Against Vaginal Shedding and Infertility

Abstract

Background: Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen worldwide. Here, we determined the ability of a C. trachomatis recombinant major outer membrane protein (rMOMP) vaccine to elicit cross-serogroup protection.

Methods: Female C3H/HeN mice were vaccinated by mucosal and systemic routes with C. trachomatis serovar D (UW-3/Cx) rMOMP and challenged in the ovarian bursa with serovars D (UW-3/Cx), D (UCI-96/Cx), E (IOL-43), or F (N.I.1). CpG-1826 and Montanide ISA 720 were used as adjuvants.

Results: Immune responses following vaccination were more robust against the most closely related serovars. Following a genital challenge (as determined by number of mice with positive vaginal cultures, number of positive cultures, number of inclusion forming units recovered, and number of days with positive cultures) mice challenged with C. trachomatis serovars of the same complex were protected but not those challenged with serovar F (N.I.1) from a different subcomplex. Females were caged with male mice. Based on fertility rates, number of embryos, and hydrosalpinx formation, vaccinated mice were protected against challenges with serovars D (UW-3/Cx), D (UCI-96/Cx), and E (IOL-43) but not F (N.I.1).

Conclusions: This is the first subunit vaccine shown to protect mice against infection, pathology, and infertility caused by different C. trachomatis serovars.

Keywords: Chlamydia trachomatis; MOMP; cross-serogroup; mice; protection; vaccine.

Figure 1.

In vitro Chlamydia trachomatis neutralization titers. Serum samples collected the day before the genital challenge from mice immunized with D (UW-3/Cx) MOMP or EB were tested for their ability to neutralize in vitro EB from the 4 C. trachomatis isolates used to challenge the mice. Abbreviations: EB, elementary body; GMT, geometric mean titer; MOMP, major outer membrane protein. * P < .05.

Figure 2.

Chlamydia trachomatis vaginal cultures over the 6 weeks of testing. A, Percentage of mice with positive vaginal cultures. B, Percentage of positive vaginal cultures in the 6 weeks of testing. ^aP < .05 by Fisher exact test compared to own PBS control. ^bP < .1 by Fisher exact test compared to own PBS control. Abbreviations: EB, elementary body; IFU, inclusion forming unit; MEM, minimum essential medium eagle; PBS, phosphate-buffered saline; rMOMP, recombinant major outer membrane protein.

Figure 3.

Chlamydia trachomatis vaginal cultures over the 6 weeks of testing. A, Total C. trachomatis IFU shed/mouse. The horizontal lines correspond to the median IFU shed/mouse. B, Time to clearance. The horizontal lines correspond to the mean number of days to clearance. ^aP < .05 by Mann-Whitney test compared to own PBS control. ^b P < .05 by Student t test compared to own PBS control. ^cP < .1 by Student t test compared to own PBS control. Abbreviations: EB, elementary body; IFU, inclusion forming unit; MEM, minimum essential medium eagle; PBS, phosphate-buffered saline; rMOMP, recombinant major outer membrane protein.