Bacterial lysates improve the protective antibody response against respiratory viruses through Toll-like receptor 4

Hum Vaccin Immunother. 2014;10(10):2896-902. doi: 10.4161/hv.29784. Epub 2014 Nov 19.

Abstract

Respiratory viruses cause significant morbidity and mortality in infants and young children worldwide. Current strategies to modulate the immune system and prevent or treat respiratory viral infections in this age group have shown limited success. Here, we demonstrate that a lysate derived from Gram-positive and Gram-negative organisms positively modulates protective antibody responses against both respiratory syncytial virus (RSV) and influenza virus in murine models of infection. Interestingly, despite the complex mixture of Toll-like receptor (TLR) agonists present in the bacterial lysate, the modulatory effects were mostly dependent on TLR4 signaling. Our results indicate that the use of simple formulations of TLR-agonists can significantly improve the immune response against critical pediatric respiratory pathogens.

Keywords: RSV; adjuvants; bacterial; extracts; immunomodulators; influenza; lysates; respiratory; virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Cell Extracts / therapeutic use*
  • Cell Line
  • Gram-Negative Bacteria / immunology
  • Gram-Negative Bacteria / metabolism
  • Gram-Positive Bacteria / immunology
  • Gram-Positive Bacteria / metabolism
  • HEK293 Cells
  • Humans
  • Interleukin-1beta / biosynthesis
  • Interleukin-6 / biosynthesis
  • Leukocytes, Mononuclear / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae / immunology
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / prevention & control*
  • Respiratory Syncytial Viruses / immunology
  • Signal Transduction / immunology
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / immunology*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Broncho-Vaxom
  • Cell Extracts
  • IL1B protein, mouse
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • TLR2 protein, human
  • TLR4 protein, human
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha