Live attenuated influenza A virus vaccine protects against A(H1N1)pdm09 heterologous challenge without vaccine associated enhanced respiratory disease

Virology. 2014 Dec:471-473:93-104. doi: 10.1016/j.virol.2014.10.003. Epub 2014 Oct 28.

Abstract

Live-attenuated influenza virus (LAIV) vaccines may provide cross-protection against contemporary influenza A virus (IAV) in swine. Conversely, whole inactivated virus (WIV) vaccines have the potential risk of vaccine-associated enhanced respiratory disease (VAERD) when challenged with IAV of substantial antigenic drift. A temperature sensitive, intranasal H1N2 LAIV was compared to wild type exposure (WT) and an intramuscular WIV vaccine in a model shown to induce VAERD. WIV vaccinated swine challenged with pandemic A/H1N1 (H1N1pdm09) were not protected from infection and demonstrated severe respiratory disease consistent with VAERD. Lung lesions were mild and challenge virus was not detected in the respiratory tract of LAIV vaccinates. High levels of post-vaccination IgG serum antibodies targeting the H1N1pdm09 HA2 stalk domain were exclusively detected in the WIV group and associated with increased H1N1pdm09 virus infectivity in MDCK cells. In contrast, infection-enhancing antibodies were not detected in the serum of LAIV vaccinates and VAERD was not observed.

Keywords: Enhanced pneumonia; Influenza A; Live attenuated influenza virus; Pandemic H1N1; Swine; Whole inactivated virus.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Viral / analysis
  • Antibodies, Viral / blood
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / analysis
  • Dogs
  • Female
  • Immunity, Mucosal
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A Virus, H1N2 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Lung / pathology
  • Madin Darby Canine Kidney Cells
  • Male
  • Orthomyxoviridae Infections / prevention & control
  • Orthomyxoviridae Infections / veterinary*
  • Orthomyxoviridae Infections / virology
  • Swine
  • Swine Diseases / immunology
  • Swine Diseases / prevention & control*
  • Swine Diseases / virology
  • Trachea / immunology
  • Trachea / pathology
  • Vaccines, Attenuated / immunology
  • Vaccines, Inactivated / immunology

Substances

  • Antibodies, Viral
  • Cytokines
  • Influenza Vaccines
  • Vaccines, Attenuated
  • Vaccines, Inactivated