Generation of protective immunity by inactivated recombinant staphylococcal enterotoxin B vaccine in nonhuman primates and identification of correlates of immunity

At this time there are no vaccines or therapeutics to protect against staphylococcal enterotoxin B (SEB) exposure. Here, we report vaccine efficacy of an attenuated SEB in a nonhuman primate model following lethal aerosol challenge and identify several biomarkers of protective immunity. Initial in v...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 108(2003), 1 vom: 16. Juli, Seite 51-9
1. Verfasser: Boles, James W (VerfasserIn)
Weitere Verfasser: Pitt, M Louise M, LeClaire, Ross D, Gibbs, Paul H, Torres, Edna, Dyas, Beverly, Ulrich, Robert G, Bavari, Sina
Format: Aufsatz
Sprache:English
Veröffentlicht: 2003
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Cytokines Enterotoxins Histocompatibility Antigens Class II Vaccines, Inactivated Vaccines, Synthetic enterotoxin B, staphylococcal 39424-53-8
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100 1 |a Boles, James W  |e verfasserin  |4 aut 
245 1 0 |a Generation of protective immunity by inactivated recombinant staphylococcal enterotoxin B vaccine in nonhuman primates and identification of correlates of immunity 
264 1 |c 2003 
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520 |a At this time there are no vaccines or therapeutics to protect against staphylococcal enterotoxin B (SEB) exposure. Here, we report vaccine efficacy of an attenuated SEB in a nonhuman primate model following lethal aerosol challenge and identify several biomarkers of protective immunity. Initial in vitro results indicated that the mutation of key amino acid residues in the major histocompatibility complex (MHC) class II binding sites of SEB produced a nontoxic form of SEB, which had little to no detectable binding to MHC class II molecules, and lacked T-cell stimulatory activities. When examined in a mouse model, we found that the attenuated SEB retained antigenic structures and elicited protective immune responses against wild-type SEB challenge. Subsequently, a vaccine regimen against SEB in a nonhuman primate model was partially optimized, and investigations of immune biomarkers as indicators of protection were performed. SEB-naïve rhesus monkeys were vaccinated two or three times with 5 or 20 microg of the attenuated SEB and challenged by aerosol with wild-type SEB toxin. Unlike exposure to the native toxin, the vaccine did not trigger the release of inflammatory cytokines (TNF alpha, IL6, or IFN gamma). All rhesus monkeys that developed anti-SEB serum titers > or = 10(4) and elicited high levels of neutralizing antibody survived the aerosol challenge. These findings suggest that the attenuated SEB is fully protective against aerosolized toxin when administered to unprimed subjects. Moreover, experiments presented in this study identified various biomarkers that showed substantial promise as correlates of immunity and surrogate endpoints for assessing in vivo biological responses in primates, and possibly in humans, to vaccines against SEs 
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650 7 |a Enterotoxins  |2 NLM 
650 7 |a Histocompatibility Antigens Class II  |2 NLM 
650 7 |a Vaccines, Inactivated  |2 NLM 
650 7 |a Vaccines, Synthetic  |2 NLM 
650 7 |a enterotoxin B, staphylococcal  |2 NLM 
650 7 |a 39424-53-8  |2 NLM 
700 1 |a Pitt, M Louise M  |e verfasserin  |4 aut 
700 1 |a LeClaire, Ross D  |e verfasserin  |4 aut 
700 1 |a Gibbs, Paul H  |e verfasserin  |4 aut 
700 1 |a Torres, Edna  |e verfasserin  |4 aut 
700 1 |a Dyas, Beverly  |e verfasserin  |4 aut 
700 1 |a Ulrich, Robert G  |e verfasserin  |4 aut 
700 1 |a Bavari, Sina  |e verfasserin  |4 aut 
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