Irradiated whole cell Chlamydia vaccine confers significant protection in a murine genital tract challenge model

Kieran C Broder; Vera Y Matrosova; Rok Tkavc; Elena K Gaidamakova; Lam Thuy Vi Tran Ho; Andrew N Macintyre; Anthony Soc; Aissata Diallo; Stephen C Darnell; Sarah Bash; Michael J Daly; Ann E Jerse; George W Liechti

doi:10.1038/s41541-024-00968-z

Irradiated whole cell Chlamydia vaccine confers significant protection in a murine genital tract challenge model

NPJ Vaccines. 2024 Nov 11;9(1):207. doi: 10.1038/s41541-024-00968-z.

Authors

Kieran C Broder^{1

2

3}, Vera Y Matrosova^{2

4}, Rok Tkavc^{1

2}, Elena K Gaidamakova^{2

4}, Lam Thuy Vi Tran Ho^{1

2}, Andrew N Macintyre⁵, Anthony Soc^{1

2}, Aissata Diallo^{1

2}, Stephen C Darnell^{1

2}, Sarah Bash^{1

2}, Michael J Daly⁶, Ann E Jerse⁷, George W Liechti⁸

Affiliations

¹ Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
² Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
³ Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biological Sciences, Colorado State University, Ft. Collins, CO, USA.
⁴ Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
⁵ Department of Medicine, Duke Human Vaccine Institute, Durham, NC, USA.
⁶ Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. michael.daly@usuhs.edu.
⁷ Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. ann.jerse1@usuhs.edu.
⁸ Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. george.liechti@usuhs.edu.

Abstract

Chlamydia trachomatis infections are the most common bacterial STIs globally and can lead to serious morbidity if untreated. Development of a killed, whole-cell vaccine has been stymied by coincident epitope destruction during inactivation. Here, we present a prototype Chlamydia vaccine composed of elementary bodies (EBs) from the related mouse pathogen, Chlamydia muridarum (Cm). EBs inactivated by gamma rays (Ir-Cm) in the presence of the antioxidant Mn²⁺-Decapeptide (DEHGTAVMLK) Phosphate (MDP) are protected from epitope damage but not DNA damage. Cm EBs gamma-inactivated with MDP retain their structure and provide significant protection in a murine genital tract infection model. Mice vaccinated with Ir-Cm (+MDP) exhibited elevated levels of Cm-specific IgG and IgA antibodies, reduced bacterial burdens, accelerated clearance, and distinctive cytokine responses compared to unvaccinated controls and animals vaccinated with EBs irradiated without MDP. Preserving EB epitopes with MDP during gamma inactivation offers the potential for a polyvalent, whole-cell vaccine against C. trachomatis.

Abstract

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