Evaluation of adenovirus 19a as a novel vector for mucosal vaccination against influenza A viruses

Vaccine. 2018 May 3;36(19):2712-2720. doi: 10.1016/j.vaccine.2018.02.075. Epub 2018 Apr 5.

Abstract

Since preexisting immunity and enhanced infection rates in a clinical trial of an HIV vaccine have raised some concerns on adenovirus (Ad) serotype 5-based vaccines, we evaluated the subgroup D adenovirus serotype Ad19a for its suitability as novel viral vector vaccine against mucosal infections. In BALB/c mice, we compared the immunogenicity and efficacy of E1/E3-deleted Ad19a vectors encoding the influenza A virus (IAV)-derived antigens hemagglutinin (HA) and nucleoprotein (NP) to the most commonly used Ad5 vectors. The adenoviral vectors were applied intranasally and induced detectable antigen-specific T cell responses in the lung and in the spleen as well as robust antibody responses. A prior DNA immunization significantly improved the immunogenicity of both vectors and resulted in full protection against a lethal infection with a heterologous H3N2 virus. Nevertheless, the Ad5-based vectors were slightly superior in reducing viral replication in the lung which corresponded to higher NP-specific T cell responses measured in the lungs.

Keywords: Ad19a; Ad5; Adenoviral vectors; Influenza A virus; Mucosal vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adenoviruses, Human / genetics*
  • Animals
  • Female
  • Gene Expression
  • Genetic Vectors / immunology*
  • Humans
  • Immunity, Humoral
  • Immunity, Mucosal
  • Influenza A Virus, H3N2 Subtype / pathogenicity
  • Influenza A virus / pathogenicity
  • Influenza Vaccines / immunology
  • Influenza Vaccines / pharmacology*
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / prevention & control*
  • T-Lymphocytes / immunology
  • Vaccines, DNA / immunology
  • Vaccines, DNA / pharmacology*

Substances

  • Influenza Vaccines
  • Vaccines, DNA