TBA 225 , a fusion toxoid vaccine for protection and broad neutralization of staphylococcal superantigens

14Citations
Citations of this article
19Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Superantigens (SAgs) play a major role in the pathogenesis of Staphylococcus aureus and are associated with several diseases, including food poisoning, bacterial arthritis, and toxic shock syndrome. Monoclonal antibodies to these SAgs, primarily TSST-1, SEB and SEA have been shown to provide protection in animal studies and to reduce clinical severity in bacteremic patients. Here we quantify the pre-existing antibodies against SAgs in many human plasma and IVIG samples and demonstrate that in a major portion of the population these antibody titers are suboptimal and IVIG therapy only incrementally elevates the anti-SAg titers. Our in vitro neutralization studies show that a combination of antibodies against SEA, SEB,and TSST-1 can provide broad neutralization of staphylococcal SAgs. We report a single fusion protein (TBA 225 ) consisting of the toxoid versions of TSST-1, SEB and SEA and demonstrate its immunogenicity and protective efficacy in a mouse model of toxic shock. Antibodies raised against this fusion vaccine provide broad neutralization of purified SAgs and culture supernatants of multiple clinically relevant S. aureus strains. Our data strongly supports the use of this fusion protein as a component of an anti-virulence based multivalent toxoid vaccine against S. aureus disease.

Cite

CITATION STYLE

APA

Venkatasubramaniam, A., Adhikari, R. P., Kort, T., Liao, G. C., Conley, S., Abaandou, L., … Aman, M. J. (2019). TBA 225 , a fusion toxoid vaccine for protection and broad neutralization of staphylococcal superantigens. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-39890-z

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free