Two Potential Syphilis Vaccine Candidates Inhibit Dissemination of Treponema pallidum.

Man Xu,Yimou Wu,Feijun Zhao,Haodang Luo,Yafeng Xie,Tiebing Zeng,Manyi Tan,Kang Zheng

doi:10.3389/fimmu.2021.759474

Abstract

Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a major public health problem worldwide. Recent increases in the number of syphilis cases, in addition to the lack of an efficient vaccine against T. pallidum for humans, highlights an urgent need for the design and development of an efficacious syphilis vaccine. Here, we assess the vaccine potential of the adhesion protein Tp0136 and the outer membrane protein Tp0663. Rabbits were subcutaneously immunized with recombinant proteins Tp0136, Tp0663, or control PBS. Immunization with Tp0136 or Tp0663 generated a strong humoral immune response with high titers of IgG, as assessed by ELISA. Moreover, animals immunized with Tp0136 or Tp0663 exhibited attenuated lesion development, increased cellular infiltration at the lesion sites, and inhibition of treponemal dissemination to distant organs compared to the unimmunized animals. These findings indicate that Tp0136 and Tp0663 are promising syphilis vaccine candidates. Furthermore, these results provide novel and important information for not only understanding the pathogenic mechanisms of spirochetes, but also the development of spirochete-specific subunit vaccines.

Highlights

Syphilis, caused by the spirochetal bacterium Treponema pallidum subsp. pallidum (T. pallidum), continues to be a globally prevalent disease, with an estimated burden of 36 million cases worldwide [1]
We investigated if immunization with the putative outer membrane protein Tp0663 and adhesion protein Tp0136 were able to induce a sufficiently strong and specific immune response in rabbits, thereby offering protection against T. pallidum infection
The histological analysis of primary lesion sites in our study revealed an increase in the cellular infiltration in Tp0663-immunized and Tp0136-immunized animals at day 21 post-challenge

Summary

Introduction

Syphilis, caused by the spirochetal bacterium Treponema pallidum subsp. pallidum (T. pallidum), continues to be a globally prevalent disease, with an estimated burden of 36 million cases worldwide [1]. Pallidum (T. pallidum), continues to be a globally prevalent disease, with an estimated burden of 36 million cases worldwide [1]. The incidence of congenital syphilis infections is on the rise, with an estimated 1.36 million pregnant women infected worldwide each year, and approximately 520,000 of these pregnancies result in adverse outcomes [8]. New Potential Syphilis Vaccine Candidates complement the traditional screening and treatment approaches for the global elimination of syphilis, especially considering the increasing prevalence of syphilis worldwide. Tp0663, a putative outer membrane protein that has surface-exposed epitopes [14], reacts strongly with serum antibodies from syphilis patients and T. pallidum-infected rabbits [15, 16], implying that it may have the potential to be a candidate vaccine

Methods

Results

Conclusion