title: Ns1 is a key protein in the vaccine composition to protect Ifnar(-/-) mice against infection with multiple serotypes of African horse sickness virus.
abstract: African horse sickness virus (AHSV) belongs to the genus Orbivirus. We have now engineered naked DNAs and recombinant modified vaccinia virus Ankara (rMVA) expressing VP2 and NS1 proteins from AHSV-4. IFNAR((-/-)) mice inoculated with DNA/rMVA-VP2,-NS1 from AHSV-4 in an heterologous prime-boost vaccination strategy generated significant levels of neutralizing antibodies specific of AHSV-4. In addition, vaccination stimulated specific T cell responses against the virus. The vaccine elicited partial protection against an homologous AHSV-4 infection and induced cross-protection against the heterologous AHSV-9. Similarly, IFNAR((-/-)) mice vaccinated with an homologous prime-boost strategy with rMVA-VP2-NS1 from AHSV-4 developed neutralizing antibodies and protective immunity against AHSV-4. Furthermore, the levels of immunity were very high since none of vaccinated animals presented viraemia when they were challenged against the homologous AHSV-4 and very low levels when they were challenged against the heterologous virus AHSV-9. These data suggest that the immunization with rMVA/rMVA was more efficient in protection against a virulent challenge with AHSV-4 and both strategies, DNA/rMVA and rMVA/rMVA, protected against the infection with AHSV-9. The inclusion of the protein NS1 in the vaccine formulations targeting AHSV generates promising multiserotype vaccines.
authors.affiliation: Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: de la Poza
authors.forename: Eva
authors.initials: E
authors.lastname: Calvo-Pinilla
authors.forename: Elena
authors.initials: E
authors.lastname: López-Gil
authors.forename: Alejandro
authors.initials: A
authors.lastname: Marín-López
authors.forename: Francisco
authors.initials: F
authors.lastname: Mateos
authors.forename: Javier
authors.initials: J
authors.lastname: Castillo-Olivares
authors.forename: Gema
authors.initials: G
authors.lastname: Lorenzo
authors.forename: Javier
authors.initials: J
authors.lastname: Ortego
mesh_terms: D000355:African Horse Sickness / Q000276:immunology* / Q000517:prevention & control; D000356:African Horse Sickness Virus / Q000145:classification / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D006736:Horses; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: C508032:Ifnar1 protein, mouse; C089209:NS1 protein, African horse sickness virus; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines; D053633:Receptor, Interferon alpha-beta
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