Protection with recombinant Clostridium botulinum C1 and D binding domain subunit (Hc) vaccines against C and D neurotoxins

Abstract 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 ch...

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Veröffentlicht in:	Vaccine 2007-05, Vol.25 (21), p.4273-4282
Hauptverfasser:	Webb, Robert P, Smith, Theresa J, Wright, Patrick M, Montgomery, Vicki A, Meagher, Michael M, Smith, Leonard A
Format:	Artikel
Sprache:	eng
Schlagworte:	Allergy and Immunology Amino Acid Sequence Animals Applied microbiology Bacterial Vaccines - genetics Bacterial Vaccines - immunology Base Sequence Biological and medical sciences Botulinum neurotoxin subtypes Botulinum Toxins - genetics Botulinum Toxins - immunology Botulism - immunology Botulism - prevention & control Clostridium botulinum Clostridium botulinum - genetics Clostridium botulinum - immunology Disease Models, Animal DNA, Bacterial - chemistry DNA, Bacterial - genetics Enzyme-Linked Immunosorbent Assay Female Fundamental and applied biological sciences. Psychology Mice Microbiology Molecular Sequence Data Pichia - genetics Pichia - metabolism Pichia pastoris Receptor-binding domain Recombinant vaccine Sequence Alignment Sequence Analysis, DNA Survival Analysis Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) Vaccines, Subunit - genetics Vaccines, Subunit - immunology Vaccines, Subunit - isolation & purification Vaccines, Synthetic - genetics Vaccines, Synthetic - immunology Vaccines, Synthetic - isolation & purification
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Zusammenfassung:	Abstract 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.
ISSN:	0264-410X 1873-2518
DOI:	10.1016/j.vaccine.2007.02.081