Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

Author:

Koroleva Ekaterina A.1ORCID,Kobets Natalie V.1ORCID,Shcherbinin Dmitrii N.1,Zigangirova Naylia A.1,Shmarov Maxim M.1,Tukhvatulin Amir I.1,Logunov Denis Y.1,Naroditsky Boris S.1,Gintsburg Alexander L.1

Affiliation:

1. Gamaleya Institute of Epidemiology and Microbiology, Ministry of Health of Russian Federation, Gamaleya Street 18, Moscow 123098, Russia

Abstract

Chlamydia trachomatisimposes serious health problems and causes infertility. Because of asymptomatic onset, it often escapes antibiotic treatment. Therefore, vaccines offer a better option for the prevention of unwanted inflammatory sequelae. The existence of serologically distinct serovars ofC. trachomatissuggests that a vaccine will need to provide protection against multiple serovars.Chlamydiaspp. use a highly conserved type III secretion system (T3SS) composed of structural and effector proteins which is an essential virulence factor. In this study, we expressed the T3SS needle protein ofChlamydia muridarum,TC_0037, an ortholog ofC. trachomatisCdsF, in a replication-defective adenoviral vector (AdTC_0037) and evaluated its protective efficacy in an intravaginalChlamydia muridarummodel. For better immune responses, we employed a heterologous prime-boost immunization protocol in which mice were intranasally primed with AdTC_0037 and subcutaneously boosted with recombinant TC_0037 and Toll-like receptor 4 agonist monophosphoryl lipid A mixed in a squalene nanoscale emulsion. We found that immunization with TC_0037 antigen induced specific humoral and T cell responses, decreasedChlamydialoads in the genital tract, and abrogated pathology of upper genital organs. Together, our results suggest that TC_0037, a highly conserved chlamydial T3SS protein, is a good candidate for inclusion in aChlamydiavaccine.

Funder

Government Program of the Russian Federation

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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