Protection with recombinant Clostridium botulinum C1 and D binding domain subunit (Hc) vaccines against C and D neurotoxins.
Recombinant botulinum Hc (rBoNT Hc) vaccines for serotypes C1 and D were produced in the yeast Pichia pastoris and used to determine protection against four distinct BoNT C and D toxin subtypes. Mice were vaccinated with rBoNT/C1 Hc, rBoNT/D Hc, or with a combination of both vaccines and challenged with BoNT C1, D, C/D, or D/C toxin. Mice receiving monovalent vaccinations were partially or completely protected against homologous toxin and not protected against heterologous toxin. Bivalent vaccine candidates completely survived challenges from all toxins except D/C toxin. These results indicate the recombinant C1 and D Hc vaccines are not only effective in a monovalent formula but offer complete protection against both parental and C/D mosaic toxin and partial protection against D/C mosaic toxin when delivered as a bivalent vaccine.
Webb
Robert P
RP
Integrated Toxicology Division, United States Army Medical Research Institute for Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, United States.
Smith
Theresa J
TJ
Wright
Patrick M
PM
Montgomery
Vicki A
VA
Meagher
Michael M
MM
Smith
Leonard A
LA
D000595:Amino Acid Sequence; D000818:Animals; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D001905:Botulinum Toxins / Q000235:genetics / Q000276:immunology*; D001906:Botulism / Q000276:immunology / Q000517:prevention & control*; D003014:Clostridium botulinum / Q000235:genetics / Q000276:immunology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D008969:Molecular Sequence Data; D010843:Pichia / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification
D001428:Bacterial Vaccines; D004269:DNA, Bacterial; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C096325:botulinum toxin type D; D001905:Botulinum Toxins; C096324:botulinum toxin type C