Modified clostridial neurotoxins as vaccine and conjugate vaccine platforms
AssigneesThe Medical College of Wisconsin, Inc., Wisconsin Alumni Research Foundation
InventorsJoseph T. Barbieri, Eric A. Johnson, Sabine Pellett, William H. Tepp, Amanda Przedpelski
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Abstract
Provided herein are engineered non-catalytic, non-toxic tetanus toxin variants and methods of using such engineered tetanus toxin variants as low dose, protective vaccines that are non-toxic and more potent than their respective chemically inactivated toxoids. In addition, provided herein are conjugate vaccine carriers comprising engineered tetanus toxin variants and methods of using such conjugate vaccines to elicit T-cell dependent immune memory responses which can target a broad spectrum of microbial pathogens as a single vaccine.
Claims16
A modified tetanus toxin polypeptide comprising a sequence having mutations R372A, Y375F, R1226L, and W1289A, and further comprising a mutation at least at one position selected from D767A, K768A and E769A, wherein each position is numbered relative to SEQ ID NO:1, the polypeptide having reduced toxicity and receptor binding compared with the toxicity and receptor binding of SEQ ID NO:1.
Dependencies are inferred from the claim text.