Development of a Chlamydia trachomatis T cell Vaccine

Abstract

The immune correlates of protection for most of the currently used vaccines are based on long-lived humoral immunity. Vaccines based on humoral immunity alone are unlikely to protect against infections caused by intracellular pathogens and today's most pressing infectious diseases of public health importance are caused by intracellular infections that not only include Chlamydia trachomatis but also tuberculosis, malaria, and HIV/AIDS. For these infections, vaccines that induce cellular immune responses are essential. Major impediments in developing such vaccines include difficulty in identifying relevant T cell antigens and delivering them in ways that elicit protective cellular immunity. In turn this is compounded by the complexity and plasticity of T cell developmental pathways that often correlate with specific aspects of protective immunity. Genomics and proteomics now provide tools to allow unbiased selection of candidate T cell antigens. This review mainly focuses on an immunoproteomic approach used in our laboratory to identify Chlamydia T cell antigens and how these T cell antigens can be developed into a future human Chlamydia vaccine.

Chlamydia trachomatis-Infected Epithelial Cells and Fibroblasts Retain the Ability To Express Surface-Presented Major Histocompatibility Complex Class I Molecules

“…The development of a C. trachomatis T cell vaccine is the current focus of many research groups (57)(58)(59). Although effective antimicrobial therapies exist, vaccination is considered to be the best approach by which to reduce the prevalence of chlamydial infections (57,60). However, currently, no vaccines against C. trachomatis infection are available, despite the many efforts that have been made throughout the years.…”

“…As chlamydial infection causes host cell DNA fragmentation and aberrant chromosomal segregation in dividing cells (39,(54)(55)(56), it is more likely that the contribution to carcinogenesis is based on DNA damage mechanisms rather than on MHC I subversion. The development of a C. trachomatis T cell vaccine is the current focus of many research groups (57)(58)(59). Although effective antimicrobial therapies exist, vaccination is considered to be the best approach by which to reduce the prevalence of chlamydial infections (57,60).…”

Profile of Anti-Chlamydia Immune Responses in Complicated (Infertile) and Non-complicated (Fertile) Genital Infections

“…In this respect, although the measured immune effectors do not necessarily implicate them in protective immunity or immunopathology, the identity of chlamydial antigens recognized by the cytokine-secreting T cells may be important for inducing protective immune responses or immunopathogenic responses, as previously suggested [8,32,33]. Besides, chlamydial immunity is T cell mediated, involving cytokine-induced anti-microbial processes that include tryptophan and essential nutrient deprivation, production of reactive nitrogen and oxygen intermediates and clearance of infected cells; while antibodies have supplementary role in protective immunity [4].…”

Formulation, characterization, and expression of a recombinant MOMP Chlamydia trachomatis DNA vaccine encapsulated in chitosan nanoparticles

“…Attempts at vaccine formulation have been underway, predating the 1970s where whole organisms were tested against different serovars. 6 However, protection gained from the whole organism vaccine was short-lived and strain specific. 6 Thus, as yet there is still no approved vaccine against C. trachomatis.…”

“…6 However, protection gained from the whole organism vaccine was short-lived and strain specific. 6 Thus, as yet there is still no approved vaccine against C. trachomatis.…”