title: Live bivalent vaccine for parainfluenza and influenza virus infections.
abstract: Influenza and human parainfluenza virus infections are of both medical and economical importance. Currently, inactivated vaccines provide suboptimal protection against influenza, and vaccines for human parainfluenza virus infection are not available, underscoring the need for new vaccines against these respiratory diseases. Furthermore, to reduce the burden of vaccination, the development of multivalent vaccines is highly desirable. Thus, to devise a single vaccine that would elicit immune responses against both influenza and parainfluenza viruses, we used reverse genetics to generate an influenza A virus that possesses the coding region for the hemagglutinin/neuraminidase ectodomain of parainfluenza virus instead of the influenza virus neuraminidase. The recombinant virus grew efficiently in eggs but was attenuated in mice. When intranasally immunized with the recombinant vaccine, all mice developed antibodies against both influenza and parainfluenza viruses and survived an otherwise lethal challenge with either of these viruses. This live bivalent vaccine has obvious advantages over combination vaccines, and its method of generation could, in principle, be applied in the development of a "cocktail" vaccine with efficacy against several different infectious diseases.
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Maeda
authors.forename: Masato
authors.initials: M
authors.lastname: Hatta
authors.forename: Ayato
authors.initials: A
authors.lastname: Takada
authors.forename: Tokiko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hideo
authors.initials: H
authors.lastname: Goto
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neumann
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D004285:Dogs; D005260:Female; D005818:Genetic Engineering; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology; D022241:Parainfluenza Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000302:isolation & purification; D029082:Sendai virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000302:isolation & purification; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000235:genetics / Q000302:isolation & purification; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000302:isolation & purification; D014774:Virulence / Q000235:genetics / Q000276:immunology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007252:Influenza Vaccines; D022241:Parainfluenza Vaccines; D014613:Vaccines, Attenuated; D017778:Vaccines, Combined; D014614:Vaccines, Synthetic; C483468:hemagglutinin, human influenza A virus; D009439:Neuraminidase