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- Title
A protein subunit vaccine elicits a balanced immune response that protects against Pseudomonas pulmonary infection.
- Authors
Howlader, Debaki R.; Das, Sayan; Lu, Ti; Mandal, Rahul Shubhra; Hu, Gang; Varisco, David J.; Dietz, Zackary K.; Ratnakaram, Siva Sai Kumar; Ernst, Robert K.; Picking, William D.; Picking, Wendy L.
- 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.
- Subjects
PSEUDOMONAS diseases; LUNG infections; IMMUNE response; NOSOCOMIAL infections; KNOCKOUT mice; NEUROENDOCRINE cells; TRANSLOCATOR proteins
- Publication
NPJ Vaccines, 2023, Vol 8, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-023-00618-w