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Review

Chlamydia trachomatis vaccine development – a view on the current challenges and how to move forward

, &
Pages 1555-1567 | Received 02 Jun 2022, Accepted 19 Aug 2022, Published online: 05 Sep 2022
 

ABSTRACT

Introduction

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the world. A licensed vaccine is not yet available, but the first vaccines have entered clinical trials.

Areas covered

We describe the progress that has been made in our understanding of the type of immunity that a protective vaccine should induce, and the challenges that vaccine developers face. We also focus on the clinical development of a chlamydia vaccine. The first chlamydia vaccine candidate has now been tested in a clinical phase I trial, and another phase I trial is currently running. We discuss what it will take to continue this development and what future trial setups could look like.

Expert opinion

The chlamydia field is coming of age and the first phase I clinical trial of a C. trachomatis vaccine has been successfully completed. We expect and hope that this will motivate various stakeholders to support further development of chlamydia vaccines in humans.

Article highlights

  • C. trachomatis is associated with a variety of clinical syndromes in humans. While the global burden of trachoma is decreasing due to major improvements in sanitation and mass drug administration, the burden of urogenital C. trachomatis infections remains significant.

  • Comprehensive national control programs based on mass screening and treatment have had very little impact on the incidence of urogenital C. trachomatis infection over time.

  • An episode of urogenital C. trachomatis infection is independently associated with future risk of pelvic inflammatory disease, ectopic pregnancy, and infertility. The use of incident C. trachomatis infections or re-infections as a study endpoint thus seems appropriate for early-phase efficacy trials testing C. trachomatis vaccine candidates.

  • The occurrence of rectal C. trachomatis infections, irrespective of sexual practices, and C. trachomatis persistence in the gastrointestinal tract have important implications for vaccine development and control program. The clinical relevance of C. trachomatis infections in the gastrointestinal tract of women is poorly understood and the extent to which this should be assessed in clinical trials is debatable.

  • It is likely that similar immunologic processes lead to either the resolution of primary infection and/or development of fibrotic sequelae. Disentangling specific immune responses that lead to spontaneous resolution of infection from those responses that promote tissue damage has therefore been a major goal in chlamydia immunology and vaccinology.

  • The clinical development of vaccines against urogenital C. trachomatis infection and disease is complicated for several reasons. The first difficulty relates to the choice of an ideal study population for late-stage efficacy trials. Another difficulty relates to the lack of reliable and well-validated biomarkers for ascension of infection and disease in the female upper genital tract.

  • The most advanced vaccine against infection with C. trachomatis is the CTH522 vaccine. The vaccine antigen CTH522 is a recombinant, engineered version of the C. trachomatis major outer membrane protein (MOMP), comprising heterologous immunorepeats from four genital C. trachomatis serovars (D, E, F, and G).

  • Preclinical research on the CTH522 vaccine led to selection of the liposome-based cationic adjuvant formulation CAF®01, which has been designed for the induction of a strong cell-mediated immune response combined with antibody induction.

Declaration of interest

F Follmann is a co-inventor on a patent on vaccines against chlamydia [US10925954, EP2976355]. All rights have been assigned to Statens Serum Institut, a Danish not-for-profit institute under the Ministry of Health. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the EU Horizon Program TRACVAC [Grant agreement ID: 733373].

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