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Limited understanding of natural protective immunity to\n                    <jats:italic>S. pyogenes<\/jats:italic>\n                    hinders vaccine development. Here we describe the evolution of serological profiles to conserved vaccine antigens and serotype-specific M proteins from birth and throughout the life course in The Gambia. As placentally transferred IgG waned after birth, serological evidence of new exposure was seen in 23% of infants during the first year of life. After culture-confirmed\n                    <jats:italic>S. pyogenes<\/jats:italic>\n                    events, the highest IgG increases occurred in children younger than 2\u2009years of age after both pharyngeal and skin disease and asymptomatic carriage at both sites. Higher IgG levels against conserved vaccine antigens correlated with functional activity and were associated with protection from culture-confirmed events after adjustment for age and anti-M protein IgG levels. To our knowledge, our data provide the first evidence of protection associated with humoral immunity to conserved vaccine candidate antigens in humans.\n                  <\/jats:p>","DOI":"10.1038\/s41591-025-03868-4","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T09:04:37Z","timestamp":1754643877000},"page":"3360-3371","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Early-life serological profiles and the development of natural protective humoral immunity to Streptococcus pyogenes in a high-burden setting"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9386-1157","authenticated-orcid":false,"given":"Alexander J.","family":"Keeley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatoumata 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