Vaccination againstChlamydiaGenital Infection Utilizing the MurineC. muridarumModel

Abstract

2Chlamydia trachomatis genital infection is a worldwide public health problem, and considerable effort has been expended on developing an efficacious vaccine. The murine model of C. muridarum genital infection has been extremely useful for identification of protective immune responses and in vaccine development. Although a number of immunogenic antigens have been assessed for their ability to induce protection, the majority of studies have utilized the whole organism, the major outer membrane protein (MOMP), or the chlamydial protease-like activity factor (CPAF). These antigens, alone and in combination with a variety of immunostimulatory adjuvants, have induced various levels of protection against infectious challenge, ranging from minimal to nearly sterilizing immunity. Understanding of the mechanisms of natural infection-based immunity and advances in adjuvant biology have resulted in studies that are increasingly successful, but a vaccine licensed for use in humans has not yet been brought to fruition. Here we review immunity to chlamydial genital infection and vaccine development using the C. muridarum model.Chlamydia trachomatis, a Gram-negative obligate intracellular bacterium with a tropism for mucosal epithelial cells, is the most common cause of bacterial sexually transmitted disease in both developed and developing countries, with more than 90 million new cases occurring each year (113-115). More than 4 million new cases of C. trachomatis infection occur each year in the United States, where costs associated with treating those infections and associated complications are in excess of $2 billion annually (107). In the genital tract, infection with C. trachomatis is propagated within the single-cell columnar layer of the epithelium in the urethra of men and the endocervix of women. Within the epithelial cells, C. trachomatis undergoes a unique biphasic developmental cycle consisting of an infectious, but metabolically inert elementary body (EB) and a noninfectious, but metabolically active reticulate body (RB). After completion of the developmental cycle, the EBs are released and infect neighboring epithelial cells, thereby spreading the infection.Infection can result in acute inflammation characterized by redness, edema, and mucosal discharge and is diagnosed clinically as mucopurulent cervicitis in women and nongonococcal urethritis in men (10, 85). In women, infection can manifest as abnormal vaginal discharge and/or postcoital bleeding, while the infection is limited to the lower genital tract, and irregular uterine bleeding and/or pelvic discomfort once the infection ascends to the upper genital tract (85). Symptoms in males are generally limited to dysuria and moderate clear-to-whitish discharge (85). While these symptoms signify an infection, the absence of such symptoms does not necessarily indicate the absence of infection. It is estimated that Ͼ70% of women and 50% of men experience asymptomatic infections (15,113). Without symptoms providing the impetus, asymptomatic individuals may not seek ...

Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis

“…Major outer membrane protein (MOMP) is the most abundant chlamydial protein constituting up to 60% of the EB dry weight. As well as being an immunodominant antigen, 7 it has been shown to induce protective immunity similar to that of live bacteria. 8 In recent years, aluminum salt adjuvants have been used as carriers for TLR agonists and immunomodulatory molecules.…”

Evolution to a Chronic Disease Niche Correlates with Increased Sensitivity to Tryptophan Availability for the Obligate Intracellular Bacterium Chlamydia pneumoniae

“…An adaptive immune response is then initiated via antigen-processing cells presenting chlamydial antigens to T cells in local lymph nodes. Animal studies (73)(74)(75)(76) and, to a certain degree, human studies (73)(74)(75)(76)(77)(78) have found that IFN-␥-producing T cells are essential for resolution of chlamydial infections (72,79,80).…”

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

“…Moreover, it can cause hydrosalpinx, fibrosis, infertility, and abortion in mice (118)(119)(120)(121). C. muridarum genital infection is usually resolved in 3 to 4 weeks, and the mice are partially protected against subsequent reinfections (122,123). C. trachomatis is also used, but the infection in mice is less severe and is resolved more quickly than C. muridarum infection.…”