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A protein subunit vaccine elicits a balanced immune response that protects against Pseudomonas pulmonary infection.
- Source :
- NPJ Vaccines; 3/14/2023, Vol. 8 Issue 1, p1-11, 11p
- Publication Year :
- 2023
-
Abstract
- The opportunistic pathogen Pseudomonas aeruginosa (Pa) causes severe nosocomial infections, especially in immunocompromised individuals and the elderly. Increasing drug resistance, the absence of a licensed vaccine and increased hospitalizations due to SARS-CoV-2 have made Pa a major healthcare risk. To address this, we formulated a candidate subunit vaccine against Pa (L-PaF), by fusing the type III secretion system tip and translocator proteins with LTA1 in an oil-in-water emulsion (ME). This was mixed with the TLR4 agonist (BECC438b). Lung mRNA sequencing showed that the formulation activates genes from multiple immunological pathways eliciting a protective Th1-Th17 response following IN immunization. Following infection, however, the immunized mice showed an adaptive response while the PBS-vaccinated mice experienced rapid onset of an inflammatory response. The latter displayed a hypoxic lung environment with high bacterial burden. Finally, the importance of IL-17 and immunoglobulins were demonstrated using knockout mice. These findings suggest a need for a balanced humoral and cellular response to prevent the onset of Pa infection and that our formulation could elicit such a response. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20590105
- Volume :
- 8
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- NPJ Vaccines
- Publication Type :
- Academic Journal
- Accession number :
- 162435679
- Full Text :
- https://doi.org/10.1038/s41541-023-00618-w