Immunity against heterosubtypic influenza virus induced by adenovirus and MVA expressing nucleoprotein and matrix protein-1

Sci Rep. 2013:3:1443. doi: 10.1038/srep01443.

Abstract

Alternate prime/boost vaccination regimens employing recombinant replication-deficient adenovirus or MVA, expressing Influenza A virus nucleoprotein and matrix protein 1, induced antigen-specific T cell responses in intradermally (ID) vaccinated mice; with the strongest responses resulting from Ad/MVA immunization. In BALB/C mice the immunodominant response was shifted from the previously identified immunodominant epitope to a novel epitope when the antigen was derived from A/Panama/2007/1999 rather than A/PR/8. Alternate immunization routes did not affect the magnitude of antigen-specific systemic IFN-γ response, but higher CD8(+) T-cell IFN-γ immune responses were seen in the bronchoalveolar lavage following intransal (IN) boosting after intramuscular (IM) priming, whilst higher splenic antigen-specific CD8(+) T cell IFN-γ was seen following IM boosting. Partial protection against heterologous influenza virus challenge was achieved following either IM/IM or IM/IN but not ID/ID immunization. These data may be of relevance for the design of optimal immunization regimens for human influenza vaccines, especially for influenza-naïve infants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology*
  • Administration, Intranasal
  • Alphainfluenzavirus / immunology*
  • Alphainfluenzavirus / metabolism
  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cytokines / metabolism
  • Female
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Immunization, Secondary
  • Influenza Vaccines / biosynthesis
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology
  • Injections, Intradermal
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nucleocapsid Proteins
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Spleen / cytology
  • Spleen / metabolism
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology*
  • Viral Core Proteins / genetics
  • Viral Core Proteins / metabolism
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism

Substances

  • Cytokines
  • Influenza Vaccines
  • M1 protein, Influenza A virus
  • NP protein, Influenza A virus
  • Nucleocapsid Proteins
  • RNA-Binding Proteins
  • Viral Core Proteins
  • Viral Matrix Proteins
  • Interferon-gamma