Subunit vaccine efficacy against Botulinum neurotoxin subtypes

► High dose vaccination with HCR/A protected mice from challenge by heterologous BoNT/A subtypes. ► Low dose HCR/A vaccination yielded partial protection to heterologous BoNT/A subtype challenge. ► Vaccination with HCR/A1 elicited an A1 subtype-specific IgG response. ► Survival to heterologous BoNT/A2 challenge with HCR/A1 vaccination correlated with IgG to the denatured HCRc/A1. ► Survival to heterologous BoNT/A1 challenge with HCR/A2 vaccination correlated with IgG titers to native HCRc/A1.