DEVELOPMENT OF ENGINEERED VACCINES EFFECTIVE AGAINST STRUCTURALLY RELATED BACTERIAL SUPERANTIGENS

Staphylococcal and streptococcal superantigens ar-e exotoxins that may be linked to many human pathologies involving impaired immune functio ns. Despite considerable sequence divergence, bacterial superantigens share extensive secondary and tertiary structure and use similar struc tural strategies to bind major histocompatibility complex class II rec eptors, We produced by site-directed mutagenesis of the conserved rece ptor-binding surfaces of the superantigens staphylococcal enterotoxins A and B, These vaccines protected immunized mice and rhesus monkeys f rom lethal toxic shock. In addition, antibodies produced against each superantigen recognized and neutralized distantly related superantigen s. This antibody cross-reactivity was additive in that mixtures of sup erantigens used in immunization were more effective than single-compon ent vaccines in protecting mice from challenges with individual or mix ed superantigens. We conclude that an optimal combination of these gen etically attenuated superantigen vaccines may protect against all stru cturally related superantigens. Published by Elsevier Science Ltd. All rights reserved.