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

Michael SuperEdward J DohertyMark J CartwrightBenjamin T SeilerFernanda LangellottoNikolaos DimitrakakisDes A WhiteAlexander G StaffordMohan KarkadaAmanda R GravelineCaitlin L HorganKayla R LightbownFrank R UrenaChyenne D YeagerSami A RifaiMaxence O DellacherieAileen W LiCollin Leese-ThompsonHamza IjazAmanda R JiangVasanth ChandrasekharJustin M ScottShanda L LightbownDonald E IngberDavid J Mooney
Published in: Nature biomedical engineering (2021)
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.
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