Induction of Transmucosal Protection by Oral Vaccination with an Attenuated Chlamydia

Yihui Wang, Rongze He, Halah Winner, Marie-Claire E Gauduin, Nu Zhang, Cheng He, Guangming Zhong

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
JournalInfection and immunity
Volume91
Issue number5
DOIs
StatePublished - May 2023

Keywords

  • CMG28.51.1
  • Chlamydia muridarum
  • TC0237
  • TC0668
  • airway infection
  • attenuated
  • attenuated oral vaccine
  • genital tract infection
  • hydrosalpinx
  • oral vaccines
  • transmucosal immunity

ASJC Scopus subject areas

  • Infectious Diseases
  • Parasitology
  • Microbiology
  • Immunology

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