Chlamydia trachomatis: Protective Adaptive Responses and Prospects for a Vaccine

Abstract

Chlamydia trachomatis is the most common cause of sexually transmitted bacterial infection globally. These infections translate to a significant public health burden, particularly women's healthcare costs due to serious disease sequelae such as pelvic inflammatory disease (PID), tubal factor infertility, chronic pelvic pain, and ectopic pregnancy. There is no evidence that natural immunity can provide complete, long-term protection necessary to prevent chronic pathology, making human vaccine development critical. Vaccine design will require careful consideration of protective versus pathological host-response mechanisms in concert with elucidation of optimal antigens and adjuvants. Evidence suggests that a Th1 response, facilitated by IFN-γ-producing CD4 T cells, will be instrumental in generating long-term, sterilizing immunity. Although the role of antibodies is not completely understood, they have exhibited a protective effect by enhancing chlamydial clearance. Future work will require investigation of broadly neutralizing antibodies and antibody-augmented cellular immunity to successfully design a vaccine that potently elicits both arms of the immune response. Sterilizing immunity is the ultimate goal. However, vaccine-induced partial immunity that prevents upper genital tract infection and inflammation would be cost-effective compared to current screening and treatment strategies. In this chapter, we examine evidence from animal and human studies demonstrating protective adaptive immune responses to Chlamydia and discuss future challenges and prospects for vaccine development.

Chlamydia trachomatis Genital Infections

“…Consequently, developing an effective vaccine is a highly desired, ambitious goal (reviewed by 182183). Candidate vaccines against C. trachomatis have languished in preclinical testing but Phase I trials of chlamydial vaccine candidates are anticipated.…”

Protection of outbred mice against a vaginal challenge by a Chlamydia trachomatis serovar E recombinant major outer membrane protein vaccine is dependent on phosphate substitution in the adjuvant

“…[54][55][56][57] Despite the vigorous antibody response to chlamydia infection or in vaccine models across different mammalian species, the role of antibodies is still poorly understood with some studies reporting protection and others a disease-enhancing effect. [58][59][60] This is not surprising due to the huge heterogeneity of the antibody responses and our incomplete understanding of this critical component of the immune system. The results from in vitro experiments performed decades ago demonstrated that following a C. trachomatis infection, mice mounted humoral responses that resulted in the production of antibodies some of which were protective and others which had neutral or disease enhancing effects.…”

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“…Национальный институт аллергии и инфекционных заболеваний (NIAID) в своем докладе «Вакцины против хламидиоза: дальнейшие пути развития» [14] [15]. Хотя конечной целью является стерилизующий иммунитет, но вызываемый вакцинацией частичный иммунитет, предотвращающий инфекцию и воспаление верхних отделов половых путей, может быть экономически более выгодным, чем существующие стратегии скрининга и лечения [16]. В Таблице 2 представлены находящиеся в разработке вакцины-кандидаты против хламидиоза [17].…”