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The continuous emergence of multidrug resistant strains is narrowing the treatment options for these infections. The development of an effective S. aureus vaccine is, therefore, a global priority. We have previously developed a vaccine candidate, 132 \u0394murI \u0394dat, which is auxotrophic for D-glutamate, and protects against sepsis caused by S. aureus. In the present study, we explored the potential of this vaccine candidate to prevent staphylococcal pneumonia, by using an acute lung infection model in BALB\/c mice. Intranasal inoculation of the vaccine strain yielded transitory colonization of the lung tissue, stimulated production of relevant serum IgG and secretory IgA antibodies in the lung and distal vaginal mucosa and conferred cross-protection to acute pneumonia caused by clinically important S. aureus strains. Although these findings are promising, additional research is needed to minimize dose-dependent toxicity for safer intranasal immunization with this vaccine candidate.<\/jats:p>","DOI":"10.3390\/vaccines11020210","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T01:57:57Z","timestamp":1674007077000},"page":"210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cross-Protection against Acute Staphylococcus aureus Lung Infection in Mice by a D-Glutamate Auxotrophic Vaccine Candidate"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0418-296X","authenticated-orcid":false,"given":"Patricia","family":"Garc\u00eda","sequence":"first","affiliation":[{"name":"Department of Microbiology, University Hospital A Coru\u00f1a (CHUAC), Biomedical Research Institute A Coru\u00f1a (INIBIC), 15006 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7119-440X","authenticated-orcid":false,"given":"Maria P.","family":"Cabral","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University Hospital A Coru\u00f1a (CHUAC), Biomedical Research Institute A Coru\u00f1a (INIBIC), 15006 A Coru\u00f1a, Spain"},{"name":"Technical Services Department, CZ Vaccines S.A.U., 36400 O Porri\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Beceiro","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University Hospital A Coru\u00f1a (CHUAC), Biomedical Research Institute A Coru\u00f1a (INIBIC), 15006 A Coru\u00f1a, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8977-3269","authenticated-orcid":false,"given":"Miriam","family":"Moscoso","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University Hospital A Coru\u00f1a (CHUAC), Biomedical Research Institute A Coru\u00f1a (INIBIC), 15006 A Coru\u00f1a, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8837-0062","authenticated-orcid":false,"given":"Germ\u00e1n","family":"Bou","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University Hospital A Coru\u00f1a (CHUAC), Biomedical Research Institute A Coru\u00f1a (INIBIC), 15006 A Coru\u00f1a, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJM199808203390806","article-title":"Staphylococcus aureus infections","volume":"339","author":"Lowy","year":"1998","journal-title":"N. 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