期刊
CLINICAL IMMUNOLOGY
卷 108, 期 1, 页码 51-59出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S1521-6616(03)00066-4
关键词
bacterial superantigens; vaccine; SEB; biomarkers; aerosol
类别
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 per-formed. SEB-naive rhesus monkeys were vaccinated two or three times with 5 or 20 mug 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 (TNFalpha, IL6, or IFNgamma). All rhesus monkeys that developed anti-SEB serum titers greater than or equal to 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. (C) 2003 Elsevier Science (USA). All rights reserved.
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