Vaccination with the recombinant major outer membrane protein elicits long-term protection in mice against vaginal shedding and infertility following a Chlamydia muridarum genital challenge

Abstract

Implementation of a vaccine is likely the best approach to curtail Chlamydia trachomatis infections. The aim of this study was to determine the ability of a vaccine formulated with the recombinant major outer membrane protein (MOMP) and Th1 and Th2 adjuvants, delivered by combinations of systemic and mucosal routes, to elicit long-term protection in mice against a genital challenge with Chlamydia muridarum. As a negative control, mice were vaccinated with the recombinant Neisseria gonorrhoeae porinB, and the positive control group was immunized with C. muridarum live elementary bodies (EB). The four vaccines formulated with MOMP, as determined by the titers of IgG and neutralizing antibodies in serum, proliferative responses of T-cells stimulated with EB and levels of IFN-γ in the supernatants, elicited robust humoral and cellular immune responses over a 6-month period. Groups of mice were challenged genitally at 60, 120, or 180 days postimmunization. Based on the number of mice with positive vaginal cultures, number of positive cultures, length of time of shedding, and number of inclusion forming units recovered, MOMP vaccinated groups were significantly protected. To assess fertility, when the vaginal cultures became negative, female mice were caged with male mice and the outcome of the pregnancy evaluated. As determined by the number of pregnant mice and the number of embryos, two of the vaccine formulations protected mice up to 180 days postimmunization. To our knowledge this is the first subunit of Chlamydia vaccine that has elicited in mice significant long-term protection against a genital challenge.

Th1/Th17 T cell Tissue-Resident Immunity Increases Protection, But Is Not Required in a Vaccine Strategy Against Genital Infection With Chlamydia trachomatis

“…It should be noted that bacterial levels were measured as bacterial shedding, which during an active and ongoing infection most probably is an adequate readout to reflect vaccine-induced protection, even though it may underestimate the total number of bacteria in the tissue. Our result is in agreement with previous studies, in which mucosal immunity, generated by intranasal or intrauterine immunization, was found to increase protection ( 8 , 16 , 31 , 32 ). As mentioned above, the increased protection in the SIM group correlated with a faster, and increased, CMI and innate response in the genital tract, as well as with increased IgA levels in the vagina.…”

“…As mentioned above, the increased protection in the SIM group correlated with a faster, and increased, CMI and innate response in the genital tract, as well as with increased IgA levels in the vagina. Given the evidence that mucosal immunity can add to the protection [Figure 4, and (8,16,(31)(32)(33)], the question is whether it should be induced by a future Chlamydia vaccine. The question is important since a parenteral administration will facilitate delivery of a C. trachomatis subunit vaccine, especially when combined with other STI vaccines, and because a parenteral administration is considered more safe and practical than a mucosal vaccine (34).…”

“…The question is important since a parenteral administration will facilitate delivery of a C. trachomatis subunit vaccine, especially when combined with other STI vaccines, and because a parenteral administration is considered more safe and practical than a mucosal vaccine ( 34 ). Importantly, several studies have shown sufficient protection with a parenteral immunity ( 15 , 31 , 35 , 36 ). Furthermore, the present study showed that although SIM animals had an advantage against the first infection compared to SC animals, no advantage in the immune response could be observed against a second infection ( Figures 5 , 6 ).…”

DnaJ, A Promising Vaccine Candidate Against Ureaplasma Urealyticum Infection

“…Some scholars have pointed out that recombinant protein subunit vaccines have limited intrinsic adjuvanticity and require immunogen formulation with adjuvants [27][28][29]. Previous reports indicated a key role of Th1 cells and neutralising antibodies in protection against pathogen challenge [30][31][32].…”

Induction of Protection in Mice against a Chlamydia muridarum Respiratory Challenge by a Vaccine Formulated with the Major Outer Membrane Protein in Nanolipoprotein Particles

“…In the genital model some of these antigens decreased vaginal shedding and inflammatory responses in the upper genital tract [ 21 , 22 , 23 ]. However, only recombinant and native MOMP have elicited protection against long-term sequelae, specifically, infertility [ 24 , 25 , 26 , 27 , 28 , 29 ].…”