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A protein subunit vaccine elicits a balanced immune response that protects against Pseudomonas pulmonary infection
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.
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.
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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.
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Date
2023-03-14
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Publisher
Nature Research
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Keywords
Bacterial infection, Protein vaccines
Citation
Howlader, D.R., Das, S., Lu, T. et al. A protein subunit vaccine elicits a balanced immune response that protects against Pseudomonas pulmonary infection. npj Vaccines 8, 37 (2023). https://doi.org/10.1038/s41541-023-00618-w