Characterization of the Antibody Response to the Receptor Binding Domain of Botulinum Neurotoxin Serotypes A and E

• Published in: Infection and Immunity
• Main Authors: Baldwin, Michael R., Tepp, William H., Pier, Christina L., Bradshaw, Marite, Ho, Mengfei, Wilson, Brenda A., Fritz, Robert B., Johnson, Eric A., Barbieri, Joseph T.
• Format: Article in Journal/Newspaper
• Language: English
• Published: American Society for Microbiology 2005
• Subjects: Infectious Diseases; Immunology; Microbiology; Parasitology; Beluga; Beluga*; Alaska
• Online Access: http://dx.doi.org/10.1128/iai.73.10.6998-7005.2005; https://journals.asm.org/doi/pdf/10.1128/IAI.73.10.6998-7005.2005

ABSTRACT Clostridium botulinum neurotoxins (BoNTs) are the most toxic proteins for humans. The current clostridial-derived vaccines against BoNT intoxication have limitations including production and accessibility. Conditions were established to express the soluble receptor binding domain (heavy-chain receptor [HCR]) of BoNT serotypes A and E in Escherichia coli . Sera isolated from mice and rabbits immunized with recombinant HCR/A1 (rHCR/A1) from the classical type A-Hall strain (ATCC 3502) (BoNT/A1) and rHCR/E from BoNT serotype E Beluga (BoNT/E B ) neutralized the homologous serotype of BoNT but displayed differences in cross-recognition and cross-protection. Enzyme-linked immunosorbent assay and Western blotting showed that α-rHCR/A1 recognized epitopes within the C terminus of the HCR/A and HCR/E, while α-rHCR/E recognized epitopes within the N terminus or interface between the N and C termini of the HCR proteins. α-rHCR/E B sera possessed detectable neutralizing capacity for BoNT/A1, while α-rHCR/A1 did not neutralize BoNT/E. rHCR/A was an effective immunogen against BoNT/A1 and the Kyoto F infant strain (BoNT/A2), but not BoNT serotype E Alaska (BoNT/E A ), while rHCR/E B neutralized BoNT/E A , and under hyperimmunization conditions protected against BoNT/A1 and BoNT/A2. The protection elicited by rHCR/A1 to BoNT/A1 and BoNT/A2 and by rHCR/E B to BoNT/E A indicate that immunization with receptor binding domains elicit protection within sub-serotypes of BoNT. The protection elicited by hyperimmunization with rHCR/E against BoNT/A suggests the presence of common neutralizing epitopes between the serotypes E and A. These results show that a receptor binding domain subunit vaccine protects against serotype variants of BoNTs.