title: Intranasal adenovirus-vectored vaccine for induction of long-lasting humoral immunity-mediated broad protection against influenza in mice.
abstract: Influenza vaccines aimed at inducing antibody (Ab) responses against viral surface hemagglutinin (HA) and neuraminidase (NA) provide sterile immunity to infection with the same subtypes. Vaccines targeting viral conserved determinants shared by the influenza A viruses (IAV) offer heterosubtypic immunity (HSI), a broad protection against different subtypes. We proposed that vaccines targeting both HA and the conserved ectodomain of matrix protein 2 (M2e) would provide protection against infection with the same subtype and also HSI against other subtypes. We report here that single intranasal immunization with a recombinant adenovirus (rAd) vector encoding both HA of H5 virus and M2e (rAdH5/M2e) induced significant HA- and M2e-specific Ab responses, along with protection against heterosubtypic challenge in mice. The protection is superior compared to that induced by rAd vector encoding either HA (rAdH5), or M2e (rAdM2e). While protection against homotypic H5 virus is primarily mediated by virus-neutralizing Abs, the cross-protection is associated with Abs directed to conserved stalk HA and M2e that seem to have an additive effect. Consistently, adoptive transfer of antisera induced by rAdH5/M2e provided the best protection against heterosubtypic challenge compared to that provided by antisera derived from mice immunized with rAdH5 or rAdM2e. These results support the development of rAd-vectored vaccines encoding both H5 and M2e as universal vaccines against different IAV subtypes.
  
  
  OBJECTIVE
  Current licensed influenza vaccines provide protection limited to the infection with same virus strains; therefore, the composition of influenza vaccines has to be revised every year. We have developed a new universal influenza vaccine that is highly efficient in induction of long-lasting cross-protection against different influenza virus strains. The cross-protection is associated with a high level of vaccine-induced antibodies against the conserved stalk domain of influenza virus hemagglutinin and the ectodomain of matrix protein. The vaccine could be used to stimulate cross-protective antibodies for the prevention and treatment of influenza with immediate effect for individuals who fail to respond to or receive the vaccine in due time. The vaccine offers a new tool to control influenza outbreaks, including pandemics.
authors.affiliation: Viral Immunology Laboratory, International Vaccine Institute, Seoul, South Korea.
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Viral Immunology Laboratory, International Vaccine Institute, Seoul, South Korea.
authors.forename: Hae-Jung
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Viral Immunology Laboratory, International Vaccine Institute, Seoul, South Korea.
authors.forename: Gye-Yeong
authors.initials: GY
authors.lastname: Han
authors.affiliation: Viral Immunology Laboratory, International Vaccine Institute, Seoul, South Korea.
authors.forename: Man-Ki
authors.initials: MK
authors.lastname: Song
authors.affiliation: Gene Therapy Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pereboev
authors.affiliation: Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Jeong S
authors.initials: JS
authors.lastname: Hong
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Biotechnology and Vaccine Translational Research Center, Yonsei University, Seoul, South Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Byun
authors.affiliation: Department of Biotechnology and Vaccine Translational Research Center, Yonsei University, Seoul, South Korea.
authors.forename: Baik Lin
authors.initials: BL
authors.lastname: Seong
authors.affiliation: Viral Immunology Laboratory, International Vaccine Institute, Seoul, South Korea hhnguyen@ivi.int.
authors.forename: Huan H
authors.initials: HH
authors.lastname: Nguyen
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D056738:Cross Protection; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000235:genetics*; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000821:virology; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D004337:Drug Carriers; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C488936:M1 protein, Influenza A virus; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; C109963:hemagglutinin, avian influenza A virus