Prophylactic Multi-Subunit Vaccine against Chlamydia trachomatis: In Vivo Evaluation in Mice

Christian Lanfermann,Claudia Rheinheimer,Robert Laudeley,Carlos Alberto Guzmán,Kai Schulze,Martin Kohn,Sebastian Wintgens,Thomas Ebensen,Andreas Klos,Johannes H Hegemann

doi:10.3390/vaccines9060609

Abstract

Chlamydia trachomatis is the most frequent sexually-transmitted disease-causing bacterium. Urogenital serovars of this intracellular pathogen lead to urethritis and cervicitis. Ascending infections result in pelvic inflammatory disease, salpingitis, and oophoritis. One of 200 urogenital infections leads to tubal infertility. Serovars A–C cause trachoma with visual impairment. There is an urgent need for a vaccine. We characterized a new five-component subunit vaccine in a mouse vaccination-lung challenge infection model. Four recombinant Pmp family-members and Ctad1 from C. trachomatis serovar E, all of which participate in adhesion and binding of chlamydial elementary bodies to host cells, were combined with the mucosal adjuvant cyclic-di-adenosine monophosphate. Intranasal application led to a high degree of cross-serovar protection against urogenital and ocular strains of C. trachomatis, which lasted at least five months. Critical evaluated parameters were body weight, clinical score, chlamydial load, a granulocyte marker and the cytokines IFN-γ/TNF-α in lung homogenate. Vaccine antigen-specific antibodies and a mixed Th1/Th2/Th17 T cell response with multi-functional CD4+ and CD8+ T cells correlate with protection. However, serum-transfer did not protect the recipients suggesting that circulating antibodies play only a minor role. In the long run, our new vaccine might help to prevent the feared consequences of human C. trachomatis infections.

Highlights

Chlamydiae are Gram-negative, intracellular bacteria with a unique reproductive cycle: infective elementary bodies (EBs) induce their uptake into mucosal cells where they remain in inclusions [1]
E challenge infection as compared to control mice that had been pretreated with c-di-AMP only, or buffer (Figure 11c)
No significant decrease of MPO, TNF-α, or IFN-γ occurred due to vaccination (Figure 11d–f). These results clearly indicate that i.n. vaccination with c-di-AMP-adjuvanted 5cVAC leads in mice to a certain degree of long-term protection against C.tr

Summary

Introduction

Chlamydiae are Gram-negative, intracellular bacteria with a unique reproductive cycle: infective elementary bodies (EBs) induce their uptake into mucosal cells where they remain in inclusions [1]. In this niche, they transform to metabolically active reticulate bodies and divide until hundreds of new infectious EBs are produced and released. Chlamydiae cause infections of the urogenital, respiratory and gastrointestinal tract, and the eye. Chlamydia trachomatis and Diseases Caused by This Intracellular Bacterium. Chlamydia trachomatis (C.tr.) has 19 serovars based on the major outer membrane protein (MOMP), and over 60 genotypes [2]. Is the most frequently reported bacterium causing a sexually-transmitted disease (STD). According to WHO, there were 124 million new cases in 2016 [3]

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