Chlamydia Deficient in Plasmid-Encoded Glycoprotein 3 (pGP3) as an Attenuated Live Oral Vaccine

Despite the extensive efforts, there is still a lack of a licensed vaccine against Chlamydia trachomatis in humans. The mouse genital tract infection with Chlamydia muridarum has been used to both investigate chlamydial pathogenic mechanisms and evaluate vaccine candidates due to the C. muridarum's ability to induce mouse hydrosalpinx. C. muridarum mutants lacking the entire plasmid or deficient in only the plasmid-encoded pGP3 are highly attenuated in inducing hydrosalpinx. We now report that intravaginal immunization with these mutants as live attenuated vaccines protected mice from hydrosalpinx induced by wild type C. muridarum. However, these mutants still productively infected the mouse genital tract. Further, the mutant-infected mice were only partially protected against the subsequent infection with wild type C. muridarum. Thus, these mutants as vaccines are neither safe nor effective when they are delivered via the genital tract. Interestingly, these mutants were highly deficient in colonizing the gastrointestinal tract. Particularly, the pGP3-deficient mutant failed to shed live organisms from mice following an oral inoculation, suggesting that the pGP3-deficient mutant may be developed into a safe oral vaccine. Indeed, oral inoculation with the pGP3-deficient mutant induced robust transmucosal immunity against both the infection and pathogenicity of wild type C. muridarum in the genital tract. Thus, we have demonstrated that the plasmid-encoded virulence factor pGP3 may be targeted for developing an attenuated live oral vaccine.