Inactivated and live, attenuated influenza vaccines protect mice against influenza: Streptococcus pyogenes super-infections

Vaccine. 2011 May 12;29(21):3773-81. doi: 10.1016/j.vaccine.2011.03.031. Epub 2011 Apr 8.

Abstract

Mortality associated with influenza virus super-infections is frequently due to secondary bacterial complications. To date, super-infections with Streptococcus pyogenes have been studied less extensively than those associated with Streptococcus pneumoniae. This is significant because a vaccine for S. pyogenes is not clinically available, leaving vaccination against influenza virus as our only means for preventing these super-infections. In this study, we directly compared immunity induced by two types of influenza vaccine, either inactivated influenza virus (IIV) or live, attenuated influenza virus (LAIV), for the ability to prevent super-infections. Our data demonstrate that both IIV and LAIV vaccines induce similar levels of serum antibodies, and that LAIV alone induces IgA expression at mucosal surfaces. Upon super-infection, both vaccines have the ability to limit the induction of pro-inflammatory cytokines within the lung, including IFN-γ which has been shown to contribute to mortality in previous models of super-infection. Limiting expression of these pro-inflammatory cytokines within the lungs subsequently limits recruitment of macrophages and neutrophils to pulmonary surfaces, and ultimately protects both IIV- and LAIV-vaccinated mice from mortality. Despite their overall survival, both IIV- and LAIV-vaccinated mice demonstrated levels of bacteria within the lung tissue that are similar to those seen in unvaccinated mice. Thus, influenza virus:bacteria super-infections can be limited by vaccine-induced immunity against influenza virus, but the ability to prevent morbidity is not complete.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / analysis*
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / analysis
  • Bronchoalveolar Lavage Fluid / microbiology
  • Bronchoalveolar Lavage Fluid / virology
  • Cytokines / analysis
  • Disease Models, Animal
  • Female
  • Immunity, Mucosal / immunology
  • Influenza Vaccines / immunology*
  • Lung / immunology
  • Lung / microbiology
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Microbial Viability
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Streptococcal Infections / prevention & control*
  • Streptococcus pyogenes / immunology
  • Superinfection / prevention & control*
  • Vaccines, Attenuated / immunology
  • Vaccines, Inactivated / immunology

Substances

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