title: A replication-incompetent influenza virus bearing the HN glycoprotein of human parainfluenza virus as a bivalent vaccine.
abstract: Influenza virus and human parainfluenza virus (HPIV) are major etiologic agents of acute respiratory illness in young children. Inactivated and live attenuated influenza vaccines are approved in several countries, yet no vaccine is licensed for HPIV. We previously showed that a replication-incompetent PB2-knockout (PB2-KO) virus that possesses a reporter gene in the coding region of the PB2 segment can serve as a platform for a bivalent vaccine. To develop a bivalent vaccine against influenza and parainfluenza virus, here, we generated a PB2-KO virus possessing the hemagglutinin-neuraminidase (HN) glycoprotein of HPIV type 3 (HPIV3), a major surface antigen of HPIV, in its PB2 segment. We confirmed that this virus replicated only in PB2-expressing cells and expressed HN. We then examined the efficacy of this virus as a bivalent vaccine in a hamster model. High levels of virus-specific IgG antibodies in sera and IgA, IgG, and IgM antibodies in bronchoalveolar lavage fluids against both influenza virus and HPIV3 were detected from hamsters immunized with this virus. The neutralizing capability of these serum antibodies was also confirmed. Moreover, the immunized hamsters were completely protected from virus challenge with influenza virus or HPIV3. These results indicate that PB2-KO virus expressing the HN of HPIV3 has the potential to be a novel bivalent vaccine against influenza and human parainfluenza viruses.
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. Electronic address: liamiiliil@gmail.com.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Iwatsuki-Horimoto
authors.forename: Maki
authors.initials: M
authors.lastname: Kiso
authors.forename: Ryuta
authors.initials: R
authors.lastname: Uraki
authors.forename: Yurie
authors.initials: Y
authors.lastname: Ichiko
authors.forename: Toru
authors.initials: T
authors.lastname: Takimoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000032:analysis / Q000097:blood; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D006224:Cricetinae; D005260:Female; D015707:HN Protein / Q000235:genetics / Q000276:immunology*; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D007075:Immunoglobulin M / Q000032:analysis / Q000097:blood; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008647:Mesocricetus; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology*; D022241:Parainfluenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000276:immunology*; D044967:Serum / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015707:HN Protein; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007252:Influenza Vaccines; D022241:Parainfluenza Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic
keywords: Antibody; Hamster; Influenza virus; Mucosal immunity; Vaccine