Superantigen vaccines: A comparative study of genetically attenuated receptor-binding mutants of staphylococcal enterotoxin A
Superantigen vaccines: A comparative study of genetically attenuated receptor-binding mutants of staphylococcal enterotoxin A
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DOI：
10.1093/infdis/174.2.338
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发表时间：
1996-08-01
影响因子：
6.4
通讯作者：
Ulrich, RG
中科院分区：
文献类型：
--
作者：
Bavari, S;Dyas, B;Ulrich, RG
超抗原通过直接结合主要组织相容性复合体（MHC）II类分子和T细胞抗原受体（TCR）发挥其病理作用，从而绕过正常的抗原特异性免疫应答。疾病和毒素之间的直接联系表明了疫苗干预的绝佳机会。开发了葡萄球菌肠毒素A（SEA）的定点突变体，其与TCR或MHC II类分子的结合减弱。两种SEA突变体作为疫苗均能诱导产生高水平的抗SEA抗体，且免疫动物在野生型毒素攻击下均能获得完全保护。然而，残余致死率与减毒TCR结合突变体相关。这些结果，结合超抗原和受体相互作用的分子性质的理解，表明通过定点诱变靶向MHC II类结合将产生最有效的疫苗。
Superantigens exert their pathologic effects by direct binding to major histocompatibility complex (MHC) class II molecules and T cell antigen receptors (TCR), thus circumventing the normal, antigen-specific immune response. A direct link between disease and toxin suggests an excellent opportunity for vaccine intervention. Site-directed mutants of staphylococcal enterotoxin A (SEA) that have attenuated binding to either the TCR or the MHC class II molecule were developed. Both kinds of SEA mutants induced high levels of antibody against SEA when used as vaccines, and the immunized animals were fully protected when challenged with wild type toxin. However, a residual lethality was associated with the attenuated TCR-binding mutant. These results, combined with an understanding of the molecular nature of superantigen and receptor interactions, indicate that targeting MHC class II binding by site-directed mutagenesis will produce the most effective vaccine.