{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T04:01:11Z","timestamp":1763179271252,"version":"build-2065373602"},"reference-count":59,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF2017-83388","BIO2017-82951-R"],"award-info":[{"award-number":["SAF2017-83388","BIO2017-82951-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["MPY 509\/19"],"award-info":[{"award-number":["MPY 509\/19"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Knowledge-based vaccinology can reveal uncharacterized antigen candidates for a new generation of protein-based anti-pneumococcal vaccines. DiiA, encoded by the sp_1992 locus, is a surface protein containing either one or two repeats of a 37mer N-terminal motif that exhibits low interstrain variability. DiiA belongs to the core proteome, contains several conserved B-cell epitopes, and is associated with colonization and pathogenesis. Immunization with DiiA protein via the intraperitoneal route induced a strong IgG response, including different IgG subtypes. Vaccination with DiiA increased bacterial clearance and induced protection against sepsis, conferring 70% increased survival at 48 h post-infection when compared to the adjuvant control. The immunogenic response and survival rates in mice immunized with a truncated DiiA version lacking 119 N-terminal residues were remarkably lower, confirming the relevance of the repeat zone in the immunoprotection by DiiA. Intranasal immunization of mice with the entire recombinant protein elicited mucosal IgG and IgA responses that reduced bacterial colonization of the nasopharynx, confirming that this protein might be a vaccine candidate for reducing the carrier rate. DiiA constitutes an example of how functionally unannotated proteins may still represent promising candidates that can be used in prophylactic strategies against the pneumococcal carrier state and invasive disease.<\/jats:p>","DOI":"10.3390\/vaccines9030187","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T06:47:20Z","timestamp":1614322040000},"page":"187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immunization with SP_1992 (DiiA) Protein of Streptococcus pneumoniae Reduces Nasopharyngeal Colonization and Protects against Invasive Disease in Mice"],"prefix":"10.3390","volume":"9","author":[{"given":"Antonio J.","family":"Mart\u00edn-Galiano","sequence":"first","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda S.","family":"Escolano-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Corsini","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adela G. de la","family":"Campa","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain"},{"name":"Presidencia Consejo Superior de Investigaciones Cient\u00edficas, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7996-0837","authenticated-orcid":false,"given":"Jos\u00e9","family":"Yuste","sequence":"additional","affiliation":[{"name":"Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain"},{"name":"CIBER de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/S0140-6736(14)61698-6","article-title":"Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: An updated systematic analysis","volume":"385","author":"Liu","year":"2015","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/S1473-3099(17)30396-1","article-title":"Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory tract infections in 195 countries: A systematic analysis for the Global Burden of Disease Study 2015","volume":"17","author":"Collaborators","year":"2017","journal-title":"Lancet Infect. 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