biostudies-literatureYan JNIAID NIH HHSeadf9556https://www.ebi.ac.uk/biostudies/studies/S-EPMC10947341biostudies-literatureUnknown15(716)Traditional vaccines are difficult to deploy against the diverse antimicrobial-resistant, nosocomial pathogens that cause health care-associated infections. We developed a protein-free vaccine composed of aluminum hydroxide, monophosphoryl lipid A, and fungal mannan that improved survival and reduced bacterial burden of mice with invasive blood or lung infections caused by methicillin-resistant <i>Staphylococcus aureus</i>, vancomycin-resistant <i>Enterococcus faecalis</i>, extended-spectrum beta-lactamase-expressing <i>Escherichia coli</i>, and carbapenem-resistant strains of <i>Acinetobacter baumannii</i>, <i>Klebsiella pneumoniae</i>, and <i>Pseudomonas aeruginosa.</i> The vaccine also conferred protection against the fungi <i>Rhizopus delemar</i> and <i>Candida albicans</i>. Efficacy was apparent by 24 hours and lasted for up to 28 days after a single vaccine dose, with a second dose restoring efficacy. The vaccine acted through stimulation of the innate, rather than the adaptive, immune system, as demonstrated by efficacy in the absence of lymphocytes that were abrogated by macrophage depletion. A role for macrophages was further supported by the finding that vaccination induced macrophage epigenetic alterations that modulated phagocytosis and the inflammatory response to infection. Together, these data show that this protein-free vaccine is a promising strategy to prevent deadly antimicrobial-resistant health care-associated infections.Science translational medicineA protein-free vaccine stimulates innate immunity and protects against nosocomial pathogens.PMC10947341R01 AI139052P30 AI028697R41 AI106375R42 AI145759R01 AI130060R42 AI106375Slarve MYan JSpellberg BWarren TKeller AEDiGiandomenico ASellman BRLuna BMTalyansky YReza HNovakovic BNielsen TBLu PNetea MGfalseA protein-free vaccine stimulates innate immunity and protects against nosocomial pathogens.Traditional vaccines are difficult to deploy against the diverse antimicrobial-resistant, nosocomial pathogens that cause health care-associated infections. We developed a protein-free vaccine composed of aluminum hydroxide, monophosphoryl lipid A, and fungal mannan that improved survival and reduced bacterial burden of mice with invasive blood or lung infections caused by methicillin-resistant <i>Staphylococcus aureus</i>, vancomycin-resistant <i>Enterococcus faecalis</i>, extended-spectrum beta-lactamase-expressing <i>Escherichia coli</i>, and carbapenem-resistant strains of <i>Acinetobacter baumannii</i>, <i>Klebsiella pneumoniae</i>, and <i>Pseudomonas aeruginosa.</i> The vaccine also conferred protection against the fungi <i>Rhizopus delemar</i> and <i>Candida albicans</i>. Efficacy was apparent by 24 hours and lasted for up to 28 days after a single vaccine dose, with a second dose restoring efficacy. The vaccine acted through stimulation of the innate, rather than the adaptive, immune system, as demonstrated by efficacy in the absence of lymphocytes that were abrogated by macrophage depletion. A role for macrophages was further supported by the finding that vaccination induced macrophage epigenetic alterations that modulated phagocytosis and the inflammatory response to infection. Together, these data show that this protein-free vaccine is a promising strategy to prevent deadly antimicrobial-resistant health care-associated infections.2023-01-01T00:00:00Z2023 Oct2025-04-26T12:07:52.278Z2025-02-19T03:08:55.739ZS-EPMC109473413779295910.1126/scitranslmed.adf9556