title: A live attenuated equine H3N8 influenza vaccine is highly immunogenic and efficacious in mice and ferrets.
abstract: Equine influenza viruses (EIV) are responsible for rapidly spreading outbreaks of respiratory disease in horses. Although natural infections of humans with EIV have not been reported, experimental inoculation of humans with these viruses can lead to a productive infection and elicit a neutralizing antibody response. Moreover, EIV have crossed the species barrier to infect dogs, pigs, and camels and therefore may also pose a threat to humans. Based on serologic cross-reactivity of H3N8 EIV from different lineages and sublineages, A/equine/Georgia/1/1981 (eq/GA/81) was selected to produce a live attenuated candidate vaccine by reverse genetics with the hemagglutinin and neuraminidase genes of the eq/GA/81 wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 (H2N2) vaccine donor virus, which is the backbone of the licensed seasonal live attenuated influenza vaccine. In both mice and ferrets, intranasal administration of a single dose of the eq/GA/81 ca vaccine virus induced neutralizing antibodies and conferred complete protection from homologous wt virus challenge in the upper respiratory tract. One dose of the eq/GA/81 ca vaccine also induced neutralizing antibodies and conferred complete protection in mice and nearly complete protection in ferrets upon heterologous challenge with the H3N8 (eq/Newmarket/03) wt virus. These data support further evaluation of the eq/GA/81 ca vaccine in humans for use in the event of transmission of an equine H3N8 influenza virus to humans.
  
  
  OBJECTIVE
  Equine influenza viruses have crossed the species barrier to infect other mammals such as dogs, pigs, and camels and therefore may also pose a threat to humans. We believe that it is important to develop vaccines against equine influenza viruses in the event that an EIV evolves, adapts, and spreads in humans, causing disease. We generated a live attenuated H3N8 vaccine candidate and demonstrated that the vaccine was immunogenic and protected mice and ferrets against homologous and heterologous EIV.
authors.affiliation: Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Baz
authors.affiliation: Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: Myeisha
authors.initials: M
authors.lastname: Paskel
authors.affiliation: Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Matsuoka
authors.affiliation: MedImmune LLC, Mountain View, California, USA.
authors.forename: James
authors.initials: J
authors.lastname: Zengel
authors.affiliation: MedImmune LLC, Mountain View, California, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Treanor
authors.affiliation: MedImmune LLC, Mountain View, California, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.affiliation: Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA ksubbarao@niaid.nih.gov.
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D056738:Cross Protection; D003429:Cross Reactions; D004195:Disease Models, Animal; D005289:Ferrets; D053123:Influenza A Virus, H3N8 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated