Immunity, immunopathology, and human vaccine development against sexually transmitted Chlamydia trachomatis

Abstract

This review examines the immunity, immunopathology, and contemporary problems of vaccine development against sexually transmitted Chlamydia trachomatis. Despite improved surveillance and treatment initiatives, the incidence of C. trachomatis infection has increased dramatically over the past 30 years in both the developed and developing world. Studies in animal models have shown that protective immunity to C. trachomatis is largely mediated by Th1 T cells producing IFN-γ which is needed to prevent dissemination of infection. Similar protection appears to develop in humans but in contrast to mice, immunity in humans may take years to develop. Animal studies and evidence from human infection indicate that immunity to C. trachomatis is accompanied by significant pathology in the upper genital tract. Although no credible evidence is currently available to indicate that autoimmunity plays a role, nevertheless, this underscores the necessity to design vaccines strictly based on chlamydial-specific antigens and to avoid those displaying even minimal sequence homologies with host molecules. Current advances in C. trachomatis vaccine development as well as alternatives for designing new vaccines for this disease are discussed. A novel approach for chlamydia vaccine development, based on targeting endogenous dendritic cells, is described.

Keywords: Chlamydia trachomatis; dendritic cells; immunity; pathology; vaccine.

Figure 1.

Model of C. trachomatis immunity and pathology. Following cervical infection, an early acute inflammatory response occurs, characterized by secretion of pro-inflammatory cytokines and recruitment of immune cells. Cytokine production by immune cells synergizes with ongoing immune responses that ultimately controls infection but also may cause pathology. C. trachomatis can ascend via the endometrium to the upper genital tract. As a consequence, local pro-inflammatory mediators and cytokines are produced. In an attempt to control the infection, Chlamydia-specific T cells and corresponding cytokines infiltrate the oviduct. These inflammatory responses, if persistent, may lead to fibrosis, scarring, and reproductive sequelae. Abbreviations: MMP, matrix metalloproteinases; SIgA, secretary immunoglobulin A; EBS, Chlamydia elementary bodies; MIP2, macrophage inflammatory protein-2.