Biomaterial vaccines capturing pathogen-associated molecular patterns protect against bacterial infections and septic shock

Nat Biomed Eng. 2022 Jan;6(1):8-18. doi: 10.1038/s41551-021-00756-3. Epub 2021 Jul 8.

Abstract

Most bacterial vaccines work for a subset of bacterial strains or require the modification of the antigen or isolation of the pathogen before vaccine development. Here we report injectable biomaterial vaccines that trigger potent humoral and T-cell responses to bacterial antigens by recruiting, reprogramming and releasing dendritic cells. The vaccines are assembled from regulatorily approved products and consist of a scaffold with absorbed granulocyte-macrophage colony-stimulating factor and CpG-rich oligonucleotides incorporating superparamagnetic microbeads coated with the broad-spectrum opsonin Fc-mannose-binding lectin for the magnetic capture of pathogen-associated molecular patterns from inactivated bacterial-cell-wall lysates. The vaccines protect mice against skin infection with methicillin-resistant Staphylococcus aureus, mice and pigs against septic shock from a lethal Escherichia coli challenge and, when loaded with pathogen-associated molecular patterns isolated from infected animals, uninfected animals against a challenge with different E. coli serotypes. The strong immunogenicity and low incidence of adverse events, a modular manufacturing process, and the use of components compatible with current good manufacturing practice could make this vaccine technology suitable for responding to bacterial pandemics and biothreats.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Infections*
  • Biocompatible Materials
  • Escherichia coli
  • Methicillin-Resistant Staphylococcus aureus*
  • Mice
  • Pathogen-Associated Molecular Pattern Molecules
  • Shock, Septic*
  • Swine
  • Vaccines*

Substances

  • Biocompatible Materials
  • Pathogen-Associated Molecular Pattern Molecules
  • Vaccines