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 MooneyPublished 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.
Keyphrases
- septic shock
- escherichia coli
- dendritic cells
- methicillin resistant staphylococcus aureus
- immune response
- candida albicans
- healthcare
- primary care
- drug delivery
- type diabetes
- adipose tissue
- tissue engineering
- dna methylation
- risk factors
- metabolic syndrome
- wound healing
- pseudomonas aeruginosa
- single molecule
- skeletal muscle
- gene expression
- cystic fibrosis
- peripheral blood
- high fat diet induced
- cancer therapy
- regulatory t cells
- high resolution
- simultaneous determination
- low density lipoprotein