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A protein subunit vaccine elicits a balanced immune response that protects against Pseudomonas pulmonary infection
dc.contributor.author | Howlader, Debaki R. | |
dc.contributor.author | Das, Sayan | |
dc.contributor.author | Lu, Ti | |
dc.contributor.author | Mandal, Rahul Shubhra | |
dc.contributor.author | Hu, Gang | |
dc.contributor.author | Varisco, David J. | |
dc.contributor.author | Dietz, Zackary K. | |
dc.contributor.author | Ratnakaram, Siva Sai Kumar | |
dc.contributor.author | Ernst, Robert K. | |
dc.contributor.author | Picking, William D. | |
dc.contributor.author | Picking, Wendy L. | |
dc.date.accessioned | 2023-04-11T18:57:39Z | |
dc.date.available | 2023-04-11T18:57:39Z | |
dc.date.issued | 2023-03-14 | |
dc.identifier.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 | en_US |
dc.identifier.uri | https://hdl.handle.net/1808/34093 | |
dc.description.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. | en_US |
dc.publisher | Nature Research | en_US |
dc.rights | © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Bacterial infection | en_US |
dc.subject | Protein vaccines | en_US |
dc.title | A protein subunit vaccine elicits a balanced immune response that protects against Pseudomonas pulmonary infection | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Howlader, Debaki R. | |
kusw.kuauthor | Lu, Ti | |
kusw.kuauthor | Hu, Gang | |
kusw.kuauthor | Dietz, Zackary K. | |
kusw.kuauthor | Ratnakaram, Siva Sai Kumar | |
kusw.kuauthor | Picking, William D. | |
kusw.kuauthor | Picking, Wendy L. | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.1038/s41541-023-00618-w | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-3170-9851 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-8939-3362 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-5016-8694 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-7998-0643 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC10012293 | en_US |
dc.rights.accessrights | openAccess | en_US |