Mucosal immunization with attenuated Shigella flexneri harboring an influenza hemagglutinin DNA vaccine protects mice against a lethal influenza challenge

Virology. 2004 Aug 1;325(2):192-9. doi: 10.1016/j.virol.2004.04.045.

Abstract

Mucosal surfaces are important for the induction of immunity against influenza virus. In a murine intranasal immunization model, we demonstrated that the attenuated Shigella flexneri Deltaasd strain 15D, carrying a DNA construct encoding the influenza virus hemagglutinin (HA), induces protective immunity against a lethal respiratory challenge with influenza A/WSN/33. Influenza virus-specific IFN-gamma T cells were detected among splenocytes, and anti-HA IgG was detected in serum post-immunization, albeit at low levels. Following influenza virus challenge, an accelerated anti-HA IgA antibody response was detected in bronchoalveolar lavage (BAL) washings from mice vaccinated with attenuated shigella containing the HA construct. These results suggest that S. flexneri Deltaasd strain 15D is a promising vector for mucosal DNA vaccine immunization against influenza virus and other mucosal pathogens.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Base Sequence
  • Female
  • Genetic Vectors
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Immunity, Mucosal*
  • Immunization
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / genetics
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Plasmids / genetics
  • Shigella flexneri / genetics*
  • Shigella flexneri / immunology*
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / genetics

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Vaccines, Attenuated
  • Vaccines, DNA