4.8 Article

Nanotoxoid vaccination protects against opportunistic bacterial infections arising from immunodeficiency

Journal

SCIENCE ADVANCES
Volume 8, Issue 36, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abq5492

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Funding

  1. Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense [HDTRA1-18-1-0014]
  2. National Institutes of Health [R21AI159492]

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This study investigates the effectiveness of a biomimetic nanotoxoid vaccine in protecting immunodeficient animals from Pseudomonas aeruginosa infection. The nanotoxoids utilize a macrophage membrane coating to sequester and present bacterial virulence factors, providing rapid and long-lasting immunity. The nanovaccine can be administered through multiple routes and effectively protects against lethal infections in pneumonia and septicemia models.
The rise in nosocomial infections caused by multidrug-resistant pathogens is a major public health concern. Patients taking immunosuppressants or chemotherapeutics are naturally more susceptible to infections. Thus, strategies for protecting immunodeficient individuals from infections are of great importance. Here, we investigate the effectiveness of a biomimetic nanotoxoid vaccine in defending animals with immunodeficiency against Pseudomonas aeruginosa. The nanotoxoids use a macrophage membrane coating to sequester and safely present bacterial virulence factors that would otherwise be too toxic to administer. Vaccination with the nanoformulation results in rapid and long-lasting immunity, protecting against lethal infections despite severe immunodeficiency. The nanovaccine can be administered through multiple routes and is effective in both pneumonia and septicemia models of infection. Mechanistically, protection is mediated by neutrophils and pathogen-specific antibodies. Overall, nanotoxoid vaccination is an attractive strategy to protect vulnerable patients and could help to mitigate the threat posed by antibiotic-resistant superbugs.

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