Protective Immunity to Chlamydia trachomatis Genital Infection: Evidence from Human Studies

Abstract

Background: Some screening and treatment programs implemented to control genital Chlamydia trachomatis infections and their complications have shown initial reductions in infection prevalence followed by rises to pre-program levels or higher. One hypothesis is that treatment shortens duration of infection, attenuates development of protective immunity and thereby increases risk of re-infection. Methods: A literature review was undertaken to assess evidence supporting the concept of protective immunity, its characteristics and its laboratory correlates in human chlamydial infection. The discussion is organized around key questions formulated in preparation for the Chlamydia Immunology and Control Expert Advisory Meeting held by the Centers for Disease Control and Prevention in April, 2008. Results: Definitive human studies are not available, but cross-sectional studies show chlamydia prevalence, organism load and concordance rates in couples decrease with age, and organism load is lower in those with repeat infections, supporting the concept of protective immunity. The protection appears partial and can be overcome upon re-exposure, similar to what is found in rodent models of genital infection. No data are available to define the duration of infection required to confer a degree of immunity or the time course of immunity following resolution of untreated infection. In longitudinal studies of African sex workers, a group presumed to have frequent and ongoing exposure to chlamydial infection, interferon gamma production by peripheral blood mononuclear cells in response to chlamydial heat shock protein 60 was associated with low risk of incident infection. In cross-sectional studies, relevant Th1 type responses are found in infected persons, paralleling the studies in animal models. Conclusions: The data support the concept that some degree of protective immunity against re-infection develops following human genital infection, although it appears at best partial. It is likely that factors besides population levels of immunity contribute to trends in prevalence observed in screening and treatment programs. Future studies of protective immunity in humans will require longitudinal follow-up of individuals and populations, frequent biological and behavioral sampling and special cohorts to help control for exposure.