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Evaluation of recombinant SEA-TSST fusion toxoid for protection against superantigen induced toxicity in mouse model

Reddy, Prakash Narayana, Paul, Soumya, Sripathy, Murali H., Batra, Harsh Vardhan
Toxicon 2015 v.103 pp. 106-113
Staphylococcus aureus, animal models, antibiotic resistance, antigens, antiserum, blood serum, cell free system, enterotoxins, immune response, immunologic memory, inflammation, lethal dose, mice, neutralization, neutralizing antibodies, resistance mechanisms, septic shock, splenocytes, toxoids, vaccines, virulence
Treatment of Staphylococcus aureus infections has become complicated owing to growing antibiotic resistance mechanisms and due to the multitude of virulence factors secreted by this organism. Failures with traditional monovalent vaccines or toxoids have brought a shift towards the use of multivalent formulas and neutralizing antibodies to combat and prevent range of staphylococcal infections. In this study, we evaluated the efficacy of a fusion protein (r-ET) comprising truncated regions of staphylococcal enterotoxin A (SEA) and toxic shock syndrome toxin (TSST-1) in generating neutralizing antibodies against superantigen induced toxicity in murine model. Serum antibodies showed specific reactivity to both SEA and TSST-1 native toxins. Hyperimmune serum from immunized animals protected cultured splenocytes from non-specific superantigen induced proliferation completely. Passive antibody administration prevented tissue damage from acute inflammation associated with superantigen challenge from S. aureus cell free culture supernatants. Approximately 80% and 50% of actively and passively immunized mice respectively were protected from lethal dose against S. aureus toxin challenge. This study revealed that r-ET protein is non-toxic and a strong immunogen which generated neutralizing antibodies and memory immune response against superantigen induced toxic effects in mice model.