Induction of Transmucosal Protection by Oral Vaccination with an Attenuated Chlamydia
Yihui Wang1,2, Rongze He1,2, Halah Winner2
1Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.
Abstract:
Chlamydia muridarum has been used to study chlamydial pathogenesis because it induces mice to develop hydrosalpinx, a pathology observed in C. trachomatis-infected women. We identified a C. muridarum mutant 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-type C. 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-type C. muridarum in the genital tract. The protection was detected as early as day 3 following the genital challenge infection and the orally 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-type C. muridarum in 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-type C. muridarum although the same mice still permitted the gastrointestinal colonization by the wild-type C. muridarum. These observations suggest that the mutant C. muridarum may be developed into an intracellular oral vaccine vector (or IntrOv) for selectively inducing transmucosal immunity in extra-gut tissues.
Insights
A novel Chlamydia muridarum mutant vaccine protects against genital and airway infections by inducing transmucosal immunity. This intracellular oral vaccine vector (IntrOv) shows potential for selective immunity induction in extra-gut tissues.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Chlamydia muridarum is a model organism for studying chlamydial pathogenesis, particularly hydrosalpinx, a condition also seen in human C. trachomatis infections.
- A C. muridarum mutant lacking hydrosalpinx-inducing capability was identified.
Purpose of the Study:
- To evaluate the potential of the C. muridarum mutant as an attenuated vaccine for inducing transmucosal immunity.
- To assess the efficacy of the mutant in protecting against wild-type C. muridarum challenge infections in various mucosal sites.
Main Methods:
- Intravaginal and oral immunization of mice with the C. muridarum mutant.
- Challenge infection with wild-type C. muridarum via vaginal, oral, and intranasal routes.
- Monitoring for hydrosalpinx, organism shedding, colonization, and immune responses.
Main Results:
- Intravaginal immunization protected against hydrosalpinx but the mutant colonized the genital tract.
- Oral inoculation with the mutant induced protective transmucosal immunity in the genital tract and airways, preventing pathology.
- Oral immunization did not prevent gastrointestinal colonization by wild-type C. muridarum.
Conclusions:
- The C. muridarum mutant shows promise as an intracellular oral vaccine vector (IntrOv) for inducing selective transmucosal immunity in extra-gut tissues.
- The IntrOv strategy could be a valuable approach for developing vaccines against various mucosal infections.
