VACCINATION AGAINST CHLAMYDIAL GENITAL-TRACT INFECTION AFTER IMMUNIZATION WITH DENDRITIC CELLS PULSED EX-VIVO WITH NONVIABLE CHLAMYDIAE

Chlamydia trachomatis, an obligate intracellular bacterial pathogen of mucosal surfaces, is a major cause of preventable blindness and sexua lly transmitted diseases for which vaccines are badly needed. Despite considerable effort, antichlamydial vaccines have proven to be elusive using conventional immunization strategies. We report the use of muri ne bone marrow-derived dendritic cells (DC) pulsed ex vivo with killed chlamydiae as a novel approach to vaccination against chlamydial infe ction. Our results show that DC efficiently phagocytose chlamydiae, se crete IL-12 p40, and present chlamydial antigen(s) to infection sensit ized CD4(+) T cells. Mice immunized intravenously with chlamydial-puls ed DC produce protective immunity against chlamydial infection of the female genital tract equal to that obtained after infection with live organisms. Immunized mice shed similar to 3 logs fewer infectious chla mydiae and are protected from genital tract inflammatory and obstructi ve disease. Protective immunity is correlated with a chlamydial-specif ic Th1-biased response that closely mimics the immune response produce d after chlamydial infection. Thus, ex vivo antigen-pulsed DC represen t a powerful tool for the study of protective immunity to chlamydial m ucosal infection and for the identification of chlamydial protective a ntigens through reconstitution experiments. Moreover, these findings m ight impact the design of vaccine strategies against other medically i mportant sexually transmitted diseases for which vaccines are sought b ut which have proven difficult to develop.