title: Mucosal immunization with a candidate universal influenza vaccine reduces virus transmission in a mouse model.
abstract: Pandemic influenza is a major public health concern, but conventional strain-matched vaccines are unavailable early in a pandemic. Candidate "universal" vaccines targeting the viral antigens nucleoprotein (NP) and matrix 2 (M2), which are conserved among all influenza A virus strains and subtypes, could be manufactured in advance for use at the onset of a pandemic. These vaccines do not prevent infection but can reduce disease severity, deaths, and virus titers in the respiratory tract. We hypothesized that such immunization may reduce virus transmission from vaccinated, infected animals. To investigate this hypothesis, we studied mouse models for direct-contact and airborne transmission of H1N1 and H3N2 influenza viruses. We established conditions under which virus transmission occurs and showed that transmission efficiency is determined in part at the level of host susceptibility to infection. Our findings indicate that virus transmission between mice has both airborne and direct-contact components. Finally, we demonstrated that immunization with recombinant adenovirus vectors expressing NP and M2 significantly reduced the transmission of virus to cohoused, unimmunized mice in comparison to controls. These findings have broad implications for the impact of conserved-antigen vaccines, not only in protecting the vaccinated individual but also in protecting others by limiting influenza virus transmission and potentially reducing the size of epidemics.
  
  
  OBJECTIVE
  Using a mouse model of influenza A virus transmission, we demonstrate that a candidate "universal" influenza vaccine both protects vaccinated animals from lethal infection and reduces the transmission of virus from vaccinated to nonvaccinated mice. This vaccine induces immunity against proteins conserved among all known influenza A virus strains and subtypes, so it could be used early in a pandemic before conventional strain-matched vaccines are available and could potentially reduce the spread of infection in the community.
authors.affiliation: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA.
authors.forename: Graeme E
authors.initials: GE
authors.lastname: Price
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Lo
authors.forename: Julia A
authors.initials: JA
authors.lastname: Misplon
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Epstein
mesh_terms: D000256:Adenoviridae; D000818:Animals; D018893:Bronchoalveolar Lavage; D016022:Case-Control Studies; D004198:Disease Susceptibility / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D006385:Hemagglutination Inhibition Tests; D018928:Immunity, Mucosal; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D009500:Neutralization Tests; D009698:Nucleoproteins / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000517:prevention & control* / Q000635:transmission*; D014763:Viral Matrix Proteins / Q000378:metabolism; D000086082:Viroporin Proteins
chemical_list: D007252:Influenza Vaccines; D009698:Nucleoproteins; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins