title: Single-dose vaccination of a recombinant parainfluenza virus 5 expressing NP from H5N1 virus provides broad immunity against influenza A viruses.
abstract: Influenza viruses often evade host immunity via antigenic drift and shift despite previous influenza virus infection and/or vaccination. Vaccines that match circulating virus strains are needed for optimal protection. Development of a universal influenza virus vaccine providing broadly cross-protective immunity will be of great importance. The nucleoprotein (NP) of influenza A virus is highly conserved among all strains of influenza A viruses and has been explored as an antigen for developing a universal influenza virus vaccine. In this work, we generated a recombinant parainfluenza virus 5 (PIV5) containing NP from H5N1 (A/Vietnam/1203/2004), a highly pathogenic avian influenza (HPAI) virus, between HN and L (PIV5-NP-HN/L) and tested its efficacy. PIV5-NP-HN/L induced humoral and T cell responses in mice. A single inoculation of PIV5-NP-HN/L provided complete protection against lethal heterosubtypic H1N1 challenge and 50% protection against lethal H5N1 HPAI virus challenge. To improve efficacy, NP was inserted into different locations within the PIV5 genome. Recombinant PIV5 containing NP between F and SH (PIV5-NP-F/SH) or between SH and HN (PIV5-NP-SH/HN) provided better protection against H5N1 HPAI virus challenge than did PIV5-NP-HN/L. These results suggest that PIV5 expressing NP from H5N1 has the potential to be utilized as a universal influenza virus vaccine.
authors.affiliation: Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.forename: Jon D
authors.initials: JD
authors.lastname: Gabbard
authors.forename: Alaina
authors.initials: A
authors.lastname: Mooney
authors.forename: Xiudan
authors.initials: X
authors.lastname: Gao
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Chen
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Place
authors.forename: S Mark
authors.initials: SM
authors.lastname: Tompkins
authors.forename: Biao
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D056738:Cross Protection; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000517:prevention & control* / Q000821:virology; D010252:Paramyxoviridae / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins