Ulrich R G, Olson M A, Bavari S
Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
Vaccine. 1998 Nov;16(19):1857-64. doi: 10.1016/s0264-410x(98)00176-5.
Staphylococcal and streptococcal superantigens are exotoxins that may be linked to many human pathologies involving impaired immune functions. Despite considerable sequence divergence, bacterial superantigens share extensive secondary and tertiary structure and use similar structural strategies to bind major histocompatibility complex class II receptors. We produced by site-directed mutagenesis of the conserved receptor-binding surfaces of the superantigens staphylococcal enterotoxins A and B. These vaccines protected immunized mice and rhesus monkeys from lethal toxic shock. In addition, antibodies produced against each superantigen recognized and neutralized distantly related superantigens. This antibody cross-reactivity was additive in that mixtures of superantigens used in immunization were more effective than single-component vaccines in protecting mice from challenges with individual or mixed superantigens. We conclude that an optimal combination of these genetically attenuated superantigen vaccines may protect against all structurally related superantigens.
葡萄球菌和链球菌超抗原是外毒素，可能与许多涉及免疫功能受损的人类疾病有关。尽管序列差异很大，但细菌超抗原具有广泛的二级和三级结构，并使用相似的结构策略来结合主要组织相容性复合体II类受体。我们通过对超抗原葡萄球菌肠毒素A和B的保守受体结合表面进行定点诱变来制备疫苗。这些疫苗保护免疫的小鼠和恒河猴免受致命的中毒性休克。此外，针对每种超抗原产生的抗体能够识别并中和远缘相关的超抗原。这种抗体交叉反应具有累加性，即免疫中使用的超抗原混合物在保护小鼠免受单个或混合超抗原攻击方面比单组分疫苗更有效。我们得出结论，这些基因减毒超抗原疫苗的最佳组合可能对所有结构相关的超抗原具有保护作用。
