title: Development of a Bacillus subtilis-based rotavirus vaccine.
abstract: Bacillus subtilis vaccine strains engineered to express either group A bovine or murine rotavirus VP6 were tested in adult mice for their ability to induce immune responses and provide protection against rotavirus challenge. Mice were inoculated intranasally with spores or vegetative cells of the recombinant strains of B. subtilis. To enhance mucosal immunity, whole cholera toxin (CT) or a mutant form (R192G) of Escherichia coli heat-labile toxin (mLT) were included as adjuvants. To evaluate vaccine efficacy, the immunized mice were challenged orally with EDIM EW murine rotavirus and monitored daily for 7 days for virus shedding in feces. Mice immunized with either VP6 spore or VP6 vegetative cell vaccines raised serum anti-VP6 IgG enzyme-linked immunosorbent assay (ELISA) titers, whereas only the VP6 spore vaccines generated fecal anti-VP6 IgA ELISA titers. Mice in groups that were immunized with VP6 spore vaccines plus CT or mLT showed significant reductions in virus shedding, whereas the groups of mice immunized with VP6 vegetative cell vaccines showed no difference in virus shedding compared with mice immunized with control spores or cells. These results demonstrate that intranasal inoculation with B. subtilis spore-based rotavirus vaccines is effective in generating protective immunity against rotavirus challenge in mice.
authors.affiliation: Department of Biomedical Sciences, Tufts University, Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA.
authors.forename: Sangun
authors.initials: S
authors.lastname: Lee
authors.forename: Boris R
authors.initials: BR
authors.lastname: Belitsky
authors.forename: James P
authors.initials: JP
authors.lastname: Brinker
authors.forename: Kathryn O
authors.initials: KO
authors.lastname: Kerstein
authors.forename: David W
authors.initials: DW
authors.lastname: Brown
authors.forename: John D
authors.initials: JD
authors.lastname: Clements
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Keusch
authors.forename: Saul
authors.initials: S
authors.lastname: Tzipori
authors.forename: Abraham L
authors.initials: AL
authors.lastname: Sonenshein
authors.forename: John E
authors.initials: JE
authors.lastname: Herrmann
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology*; D001412:Bacillus subtilis / Q000235:genetics*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000235:genetics; D036022:Capsid Proteins / Q000235:genetics* / Q000276:immunology*; D002417:Cattle; D002772:Cholera Toxin / Q000008:administration & dosage / Q000235:genetics; D004337:Drug Carriers; D004768:Enterotoxins / Q000008:administration & dosage / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000235:genetics; D005243:Feces / Q000737:chemistry / Q000821:virology; D005260:Female; D005822:Genetic Vectors; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D012400:Rotavirus Infections / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D017201:Virus Shedding
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D001427:Bacterial Toxins; D036022:Capsid Proteins; D004337:Drug Carriers; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D022243:Rotavirus Vaccines; C061332:VP6 protein, Rotavirus; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli
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