{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:16:53Z","timestamp":1785525413948,"version":"3.56.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013826","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000}}],"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["2T32AI007051"],"award-info":[{"award-number":["2T32AI007051"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1F31AI186511"],"award-info":[{"award-number":["1F31AI186511"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5R01AI156898"],"award-info":[{"award-number":["5R01AI156898"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["221803\/Z\/20\/Z"],"award-info":[{"award-number":["221803\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wellcome Investigator Award","award":["221803\/Z\/20\/Z"],"award-info":[{"award-number":["221803\/Z\/20\/Z"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["APP11997"],"award-info":[{"award-number":["APP11997"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5R01AI114800"],"award-info":[{"award-number":["5R01AI114800"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010628","name":"Universidad de La Sabana","doi-asserted-by":"crossref","award":["285 2020"],"award-info":[{"award-number":["285 2020"]}],"id":[{"id":"10.13039\/501100010628","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    (\n                    <jats:italic>Spn<\/jats:italic>\n                    ) colonization of the nasopharynx is a prerequisite for transmission and invasive disease. To investigate how repeated asymptomatic colonization shapes immunity and influences bacterial traits, we developed the Repeated Asymptomatic Murine Pneumococcal Colonization (RAMPC\n                    <jats:sub>3<\/jats:sub>\n                    ) model using strains belonging to serotypes: 2 (D39), 3 (WU2), and 4 (TIGR4). Sequential colonization revealed strain- and exposure-order-dependent effects on bacterial burden, with initial colonization yielding robust carriage and subsequent exposures resulting in diminished burden and rapid clearance. Humoral profiling demonstrated antigenic imprinting: the first colonizing strain largely determined IgG and IgA specificity against bacterial proteins, with minimal diversification or expansion after repeated exposures. Reactivity was strongest for biofilm-associated antigens correlating with each strain\u2019s biofilm-forming capacity. Notably, experiments using human sera from naturally colonized adults mirrored these findings, with reactivity favoring biofilm antigens independent from capsule. Partial protection as result of colonization was demonstrated as triple-colonized mice had reduced mortality following pneumococcal pneumonia challenge. Likewise, mice colonized with biofilm deficient versions of TIGR4 and then challenged intratracheally with a serotype 6A (6A-10) strain were more likely to develop bacteremia, underscoring the contribution of the biofilm-associated host response to immunity. Finally, IgA responses in nasal-associated lymphoid tissue paralleled serum IgA patterns, validating systemic measurements as a proxy for mucosal immunity. These results reveal that biofilm formation during colonization is a key determinant of humoral immunity and contributes to systemic protection, providing insight into pneumococcal biology and informing strategies to design next-generation interventions.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013826","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T17:36:59Z","timestamp":1785260219000},"page":"e1013826","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biofilm formation during pneumococcal carriage imprints naturally acquired humoral immunity"],"prefix":"10.1371","volume":"22","author":[{"given":"Jessica R.","family":"Lane","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Mauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia E.","family":"Santana-Krimskaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahini S.","family":"Konda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"DePass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Ercoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico 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