title: Recombinant rotavirus inner core proteins produced in the milk of transgenic rabbits confer a high level of protection after intrarectal delivery.
abstract: Development of a safe, cheap and efficient vaccine against rotavirus is important to reduce the morbidity and mortality associated with gastroenteritis in infants worldwide. High quantities of two inner core rotavirus-derived proteins (VP2 and a nonglycosylated mutant VP6 (VP6(NG)) from the RF81 bovine strain) were produced in the milk of transgenic rabbits. We show here that rectal administration of partially purified milk-derived VP2 and VP6(NG) proteins with the detoxified LT(R192G) adjuvant almost completely prevented fecal shedding induced by a highly infectious challenge in mice with the murine ECw strain. The vaccine generated rotavirus-specific fecal secretory IgA, systemic IgG and IgA and a rotavirus-specific Th1 response. We thus demonstrate in clinically feasible settings that mass production of viral protein in transgenic milk is a promising way to generate subunit vaccine against rotavirus.
authors.affiliation: Biologie du Développement et de la Reproduction, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Soler
authors.forename: Nathalie
authors.initials: N
authors.lastname: Parez
authors.forename: Bruno
authors.initials: B
authors.lastname: Passet
authors.forename: Catherine
authors.initials: C
authors.lastname: Dubuquoy
authors.forename: Sabine
authors.initials: S
authors.lastname: Riffault
authors.forename: Matthieu
authors.initials: M
authors.lastname: Pillot
authors.forename: Louis-Marie
authors.initials: LM
authors.lastname: Houdebine
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schwartz-Cornil
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008892:Milk / Q000378:metabolism; D011817:Rabbits; D012007:Rectum; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D022243:Rotavirus Vaccines; C442545:VP2 protein, Rotavirus; C061332:VP6 protein, Rotavirus; D014614:Vaccines, Synthetic