Induction of transmucosal protection by oral vaccination with an attenuatedChlamydia

Abstract

AbstractChlamydia muridarumhas been used to study chlamydial pathogenesis since it induces mice to develop hydrosalpinx, a pathology observed inC. trachomatis-infected women. We identified aC. muridarummutant that is no longer able to induce hydrosalpinx. In the current study, we evaluated the mutant as an attenuated vaccine. Following an intravaginal immunization with the mutant, mice were protected from hydrosalpinx induced by wild typeC. muridarum. However, the mutant itself productively colonized the mouse genital tract and produced infectious organisms in vaginal swabs. Nevertheless, the mutant failed to produce infectious shedding in the rectal swabs following an oral inoculation. Importantly, mice orally inoculated with the mutant mounted transmucosal immunity against challenge infection of wild typeC. muridarumin the genital tract. The protection was detected as early as day 3 following the challenge infection and the immunized mice were protected from any significant pathology in the upper genital tract. However, the same orally immunized mice failed to prevent the colonization of wild typeC. muridarumin the gastrointestinal tract. The transmucosal immunity induced by the oral mutant was further validated in the airway. The orally vaccinated mice were protected from both lung infection and systemic toxicity caused by intranasally inoculated wild typeC. muridarumalthough the same mice still permitted the gastrointestinal colonization by the wild typeC. muridarum. These observations suggest that the mutantC. muridarummay be developed into anintracellularoralvaccine vector (or IntrOv) for selectively inducing transmucosal immunity in extra-gut tissues.