PMID- 25210171 OWN - NLM STAT- MEDLINE DCOM- 20150210 LR - 20211021 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 88 IP - 22 DP - 2014 Nov TI - A bivalent vaccine based on a replication-incompetent influenza virus protects against Streptococcus pneumoniae and influenza virus infection. PG - 13410-7 LID - 10.1128/JVI.01205-14 [doi] AB - Streptococcus pneumoniae is a major causative pathogen in community-acquired pneumonia; together with influenza virus, it represents an important public health burden. Although vaccination is the most effective prophylaxis against these infectious agents, no single vaccine simultaneously provides protective immunity against both S. pneumoniae and influenza virus. Previously, we demonstrated that several replication-incompetent influenza viruses efficiently elicit IgG in serum and IgA in the upper and lower respiratory tracts. Here, we generated a replication-incompetent hemagglutinin knockout (HA-KO) influenza virus possessing the sequence for the antigenic region of pneumococcal surface protein A (PspA). Although this virus (HA-KO/PspA virus) could replicate only in an HA-expressing cell line, it infected wild-type cells and expressed both viral proteins and PspA. PspA- and influenza virus-specific antibodies were detected in nasal wash and bronchoalveolar lavage fluids and in sera from mice intranasally inoculated with HA-KO/PspA virus, and mice inoculated with HA-KO/PspA virus were completely protected from lethal challenge with either S. pneumoniae or influenza virus. Further, bacterial colonization of the nasopharynx was prevented in mice immunized with HA-KO/PspA virus. These results indicate that HA-KO/PspA virus is a promising bivalent vaccine candidate that simultaneously confers protective immunity against both S. pneumoniae and influenza virus. We believe that this strategy offers a platform for the development of bivalent vaccines, based on replication-incompetent influenza virus, against pathogens that cause respiratory infectious diseases. IMPORTANCE: Streptococcus pneumoniae and influenza viruses cause contagious diseases, but no single vaccine can simultaneously provide protective immunity against both pathogens. Here, we used reverse genetics to generate a replication-incompetent influenza virus carrying the sequence for the antigenic region of pneumococcal surface protein A and demonstrated that mice immunized with this virus were completely protected from lethal doses of infection with either influenza virus or Streptococcus pneumoniae. We believe that this strategy, which is based on a replication-incompetent influenza virus possessing the antigenic region of other respiratory pathogens, offers a platform for the development of bivalent vaccines. CI - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved. FAU - Katsura, Hiroaki AU - Katsura H AD - Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. FAU - Piao, Zhenyu AU - Piao Z AD - Laboratory of Clinical Research on Infectious Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. FAU - Iwatsuki-Horimoto, Kiyoko AU - Iwatsuki-Horimoto K AD - Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. FAU - Akeda, Yukihiro AU - Akeda Y AD - Laboratory of Clinical Research on Infectious Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. FAU - Watanabe, Shinji AU - Watanabe S AD - ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan Laboratory of Veterinary Microbiology, Department of Veterinary Sciences, University of Miyazaki, Miyazaki, Japan. FAU - Horimoto, Taisuke AU - Horimoto T AD - Department of Veterinary Microbiology, Graduate School of Agriculture and Life Science, University of Tokyo, Tokyo, Japan. FAU - Oishi, Kazunori AU - Oishi K AD - Laboratory of Clinical Research on Infectious Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan oishik@nih.go.jp kawaoka@ims.u-tokyo.ac.jp. FAU - Kawaoka, Yoshihiro AU - Kawaoka Y AD - Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan oishik@nih.go.jp kawaoka@ims.u-tokyo.ac.jp. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140910 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Bacterial Proteins) RN - 0 (Hemagglutinin Glycoproteins, Influenza Virus) RN - 0 (Influenza Vaccines) RN - 0 (Streptococcal Vaccines) RN - 0 (Vaccines, Synthetic) RN - 0 (pneumococcal surface protein A) SB - IM MH - Animals MH - Bacterial Proteins/genetics/immunology MH - Carrier State/prevention & control MH - Disease Models, Animal MH - Female MH - Gene Knockout Techniques MH - Hemagglutinin Glycoproteins, Influenza Virus/genetics MH - Humans MH - Influenza A virus/genetics/*immunology MH - Influenza Vaccines/administration & dosage/genetics/*immunology MH - Nasopharynx/microbiology MH - Orthomyxoviridae Infections/immunology/*prevention & control MH - Pneumococcal Infections/immunology/*prevention & control MH - Streptococcal Vaccines/administration & dosage/genetics/*immunology MH - Streptococcus pneumoniae/genetics/*immunology MH - Survival Analysis MH - Vaccines, Synthetic/administration & dosage/genetics/immunology PMC - PMC4249093 EDAT- 2014/09/12 06:00 MHDA- 2015/02/11 06:00 PMCR- 2015/05/01 CRDT- 2014/09/12 06:00 PHST- 2014/09/12 06:00 [entrez] PHST- 2014/09/12 06:00 [pubmed] PHST- 2015/02/11 06:00 [medline] PHST- 2015/05/01 00:00 [pmc-release] AID - JVI.01205-14 [pii] AID - 01205-14 [pii] AID - 10.1128/JVI.01205-14 [doi] PST - ppublish SO - J Virol. 2014 Nov;88(22):13410-7. doi: 10.1128/JVI.01205-14. Epub 2014 Sep 10.