Positive Contribution of Adjuvanted Influenza Vaccines to the Resolution of Bacterial Superinfections

J Infect Dis. 2016 Jun 15;213(12):1876-85. doi: 10.1093/infdis/jiw048. Epub 2016 Feb 9.

Abstract

Background: Most preclinical studies assess vaccine effectiveness in single-pathogen infection models. This is unrealistic given that humans are continuously exposed to different commensals and pathogens in sequential and mixed infections. Accordingly, complications from secondary bacterial infection are a leading cause of influenza-associated morbidity and mortality. New vaccination strategies are needed to control infections on simultaneous fronts.

Methods: We compared different anti-influenza vaccines for their protective potential in a model of viral infection with bacterial superinfection. Mice were immunized with H1N1/A/California/7/2009 subunit vaccines, formulated with different adjuvants inducing either T-helper type 1 (Th1) (MF59 plus CpG)-, Th1/2 (MF59)-, or Th17 (LTK63)-prone immune responses and were sequentially challenged with mouse-adapted influenza virus H1N1/A/Puerto Rico/8/1934 and Staphylococcus aureus USA300, a clonotype emerging as a leading contributor in postinfluenza pneumonia in humans.

Results: Unadjuvanted vaccine controlled single viral infection, yet mice had considerable morbidity from viral disease and bacterial superinfection. In contrast, all adjuvanted vaccines efficiently protected mice in both conditions. Interestingly, the Th1-inducing formulation was superior to Th1/2 or Th17 inducers.

Conclusions: Our studies should help us better understand how differential immunity to influenza skews immune responses toward coinfecting bacteria and discover novel modes to prevent bacterial superinfections in the lungs of persons with influenza.

Keywords: CpG; LTK63; MF59; Staphylococcus aureus; bacterial superinfection; influenza; vaccine adjuvants.

Publication types

  • Evaluation Study

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Bacterial Toxins / administration & dosage
  • Enterotoxins / administration & dosage
  • Escherichia coli Proteins / administration & dosage
  • Female
  • Humans
  • Immunization
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Influenza, Human / complications
  • Influenza, Human / microbiology
  • Influenza, Human / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Oligodeoxyribonucleotides / administration & dosage
  • Polysorbates / administration & dosage
  • Specific Pathogen-Free Organisms
  • Squalene / administration & dosage
  • Staphylococcal Infections / complications
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / prevention & control*
  • Staphylococcus aureus / immunology*
  • Superinfection / microbiology
  • Superinfection / prevention & control*

Substances

  • Adjuvants, Immunologic
  • Bacterial Toxins
  • Enterotoxins
  • Escherichia coli Proteins
  • Influenza Vaccines
  • MF59 oil emulsion
  • Oligodeoxyribonucleotides
  • Polysorbates
  • Squalene
  • heat-labile enterotoxin, E coli