title: Rotavirus 2/6 viruslike particles administered intranasally with cholera toxin, Escherichia coli heat-labile toxin (LT), and LT-R192G induce protection from rotavirus challenge.
abstract: We have shown that rotavirus 2/6 viruslike particles composed of proteins VP2 and VP6 (2/6-VLPs) administered to mice intranasally with cholera toxin (CT) induced protection from rotavirus challenge, as measured by virus shedding. Since it is unclear if CT will be approved for human use, we evaluated the adjuvanticity of Escherichia coli heat-labile toxin (LT) and LT-R192G. Mice were inoculated intranasally with 10 microg of 2/6-VLPs combined with CT, LT, or LT-R192G. All three adjuvants induced equivalent geometric mean titers of rotavirus-specific serum antibody and intestinal immunoglobulin G (IgG). Mice inoculated with 2/6-VLPs with LT produced significantly higher titers of intestinal IgA than mice given CT as the adjuvant. All mice inoculated with 2/6-VLPs mixed with LT and LT-R192G were totally protected (100%) from rotavirus challenge, while mice inoculated with 2/6-VLPs mixed with CT showed a mean 91% protection from challenge. The availability of a safe, effective mucosal adjuvant such as LT-R192G will increase the practicality of administering recombinant vaccines mucosally.
authors.affiliation: Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: O'Neal
authors.forename: J D
authors.initials: JD
authors.lastname: Clements
authors.forename: M K
authors.initials: MK
authors.lastname: Estes
authors.forename: M E
authors.initials: ME
authors.lastname: Conner
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000956:Antigens, Viral; D001427:Bacterial Toxins / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins; D002772:Cholera Toxin / Q000276:immunology*; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000276:immunology*; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D005260:Female; D006801:Humans; D051379:Mice; D009297:Nasal Mucosa; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014771:Virion
chemical_list: D000956:Antigens, Viral; D001427:Bacterial Toxins; D036022:Capsid Proteins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C442545:VP2 protein, Rotavirus; C061332:VP6 protein, Rotavirus; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli