TBA225, a fusion toxoid vaccine for protection and broad neutralization of staphylococcal superantigens.
Arundhathi VenkatasubramaniamRajan P AdhikariThomas KortGrant C LiaoShawn ConleyLaura AbaandouShweta KailasanYoshikuni OnoderaSubramaniam KrishnanDidier M DjagbareFrederick W HoltsbergHatice KarauzumM Javad AmanPublished in: Scientific reports (2019)
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 (TBA225) 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.
Keyphrases
- staphylococcus aureus
- mouse model
- end stage renal disease
- escherichia coli
- methicillin resistant staphylococcus aureus
- biofilm formation
- ejection fraction
- newly diagnosed
- chronic kidney disease
- rheumatoid arthritis
- case control
- prognostic factors
- pseudomonas aeruginosa
- peritoneal dialysis
- case report
- patient reported outcomes
- cystic fibrosis
- risk assessment
- climate change
- cell therapy