Protective effect of recombinant staphylococcal enterotoxin A entrapped in polylactic-co-glycolic acid microspheres against Staphylococcus aureus infection

Staphylococcus aureus (S. aureus) is an important cause of nosocomial and community-acquired infections in humans and animals, and economic loss in animal husbandry, such as mastitis in dairy cattle [1]. S. aureus can provoke clinical mastitis but more frequently causes subclinical infections that tend to become chronic and difficult to eradicate by conventional antimicrobial therapies [2,3].The frequent incapacity of both the antibiotics and immune response to prevent infection and destroy the pathogen in the intramammary environment explains why S. aureus bovine mastitis constitutes a major challenge to dairy producers [4]. Multidrug-resistant S. aureus infections continue to increase, and some strains respond to few, if any, conventional antibiotic therapies. Hence, interest in immunotherapeutic strategies, either passive or active, has seen resurgence in recent years. The pathogenicity of S. aureus results from structures that allow it to avoid phagocytosis, the production of enzymes and toxins, including exotoxins such as staphylococcal enterotoxins (SE), toxic shock syndrome toxins (TSST), exoenzymes, adhesins, and numerous cell-associated components that either directly cause disease or facilitate tissue penetration and immune cell recruitment [5,6]. Therefore, application of efficacious vaccine is one of the most important prophylactic measures against bovine mastitis.Several studies have recently focused on S. aureus toxins as vaccine targets [7-9]. SE, which are bacterial superantigens (sAg) produced by S. aureus, play an important role in establishing and maintaining infection [5]. Immunization with recombinant or mutant staphylococcal enterotoxin A (SEA) [10], staphylococcal enterotoxin B (SEB) [11-13], and TSST-1 [12,14] can elicit neutralizing antibodies against wild-type SE, and has been shown to protect mice, rabbits, and monkeys against lethal shock induced by wild-type superantigenic toxins. Hu et al. have investigated a double-mutant staphylococca