Prospects for a vaccine against Chlamydia genital disease II. — Immunity and vaccine development

Abstract

Based on available data, both published and unpublished, we propose the following model for the acquired immune response to chlamydial genital infection (fig. 1). Chlamydial EBs or chlamydial antigen through a yet undefined interaction with resident macrophages elicit the production of IL12 and TNFα which in turn recruit and activate NK cells to release IFNγ within the first few days of infection. The effect of IFNγ is two-fold: (1) it may serve to control the chlamydial infection until the acquired immune response is activated and (2) in conjunction with IL12, it effects the shift of the CD4 population to a Th1 dominant response which is required for the resolution of the infection. Since antibody to chlamydiae is produced, it would seem likely that some Th2 cells are also present which can provide help for the production of antibody, although because of the Oh1-dominant response, the main antibody produced is IgG_2a. Both antibody and CMI are required for resolution of the infection. It is hypothesized that antibody neutralizes chlamydial EBs, preventing infection or differentiation into reticulate bodies. Since some EBs most likely escape antibody and attain the intracellular environment, CMI acting via IFNγ produced by CD4 and CD8 cells would then be necessary to eliminate the organism or at least prevent replication of the organism. When individuals become reinfected, it is likely that antibody (both IgG and sIgA) in genital secretions is able to reduce the number of organisms by neutralization. The chlamydiae which avoid neutralization can go on to infect cells and may go through one or more cycles until O cells can be recruited to the area to elaborate their appropriate cytokines including IFNγ and once again control the infection. In the absence of reinfection, it is possible that when chlamydial antigen ceases to be produced by organisms in the persistent state, the immune cells will no longer be maintained in the local area. When they are gone, it is possible that the lack of IFNγ will cause the organisms to again begin replication and possibly elicit another inflammatory event. The level of the infection may be held in check by the presence of antibody in secretion.

Dans les infections génitales, la question de la défense immunitaire anti-Chlamydia peut se poser devant la fréquente persistance du microorganisme, de même que peut se poser la question de l'initiation des réponses immunitaires, humorales et cellulaires, en vue de la justification d'un vaccin. Les facteurs intervenant dans ces mécanismes sont analysés: l'immunopathologie, l'immunité de courte durée, la persistance, les influences hormonales, les facteurs génétiques, la variabilité antigénique, les infections multiples (sexuellement transmises). Les vaccins envisagés peuvent être à base de microorganismes entiers ou de composants: MOMP, Omp2, LPS, Hsp70 etc. La voie d'administration du vaccin peut également jouer un rôle. Enfin sont abordées les stratégies vaccinales dirigées contre l'infection et contre les états pathologiques.