Early-life serological profiles and the development of natural protective humoral immunity to Streptococcus pyogenes in a high-burden setting
Streptococcus pyogenes leads to 500,000 deaths annually, many due to rheumatic heart disease in low-income settings. Limited understanding of natural protective immunity to S. pyogenes 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 S. pyogenes events, the highest IgG increases occurred in children younger than 2 years 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.
Authors
- Bunja Samateh
- Luca Rovetini
- Pierre R. Smeesters (ORCID: https://orcid.org/0000-0002-2642-9919)
- Isatou Ceesay
- Elina Senghore
- Gabrielle de Crombrugghe (ORCID: https://orcid.org/0000-0003-4700-8600)
- Haddy Ceesay
- Omar Rossi (ORCID: https://orcid.org/0000-0002-0170-1285)
- Ed Clarke (ORCID: https://orcid.org/0000-0002-7785-0340)
- Lady Chilel Sanyang
- Claire E. Turner
- M. Fofana (ORCID: https://orcid.org/0000-0002-8196-7402)
- Alexander J. Keeley (ORCID: https://orcid.org/0000-0001-9386-1157)
- Michael Marks (ORCID: https://orcid.org/0000-0002-7585-4743)
- Alana L. Whitcombe (ORCID: https://orcid.org/0000-0002-1951-3469)
- Amat Bittaye
- Luisa Massai (ORCID: https://orcid.org/0009-0009-0663-2918)
- Thushan I. de Silva (ORCID: https://orcid.org/0000-0002-6498-9212)
- Edwin P. Armitage (ORCID: https://orcid.org/0000-0003-1125-4260)
- Adam J. Kucharski (ORCID: https://orcid.org/0000-0001-8814-9421)
- Nicole J. Moreland (ORCID: https://orcid.org/0000-0001-6548-637X)
- Ya Jankey Jagne (ORCID: https://orcid.org/0000-0001-5235-8475)
- Beate Kampmann (ORCID: https://orcid.org/0000-0002-6546-4709)
- Anne Botteaux (ORCID: https://orcid.org/0000-0001-9208-515X)
- Miren Iturriza‐Gómara
- Muhammed Manneh
- Danilo Gomes Moriel (ORCID: https://orcid.org/0000-0002-1421-8129)
- Martina Carducci
- Elena Boero (ORCID: https://orcid.org/0000-0001-7199-6456)
- Henrik Salje (ORCID: https://orcid.org/0000-0003-3626-4254)
- Oumar Camara (ORCID: https://orcid.org/0000-0001-9009-4773)
- Musukoi Jammeh
- Fatoumata E. Camara (ORCID: https://orcid.org/0009-0005-5003-836X)
- Jainaba Sillah
- Ebrima E. Cessay
- Victoria Rollinson
Institutions
- Université Libre de Bruxelles (BE)
- University of Auckland (NZ)
- University of Cambridge (GB)
- Royal London Hospital (GB)
- University of Bristol (GB)
- London School of Hygiene & Tropical Medicine (GB)
- Hospital for Tropical Diseases (GB)
- Queen Fabiola Children's University Hospital (BE)
- MRC Unit the Gambia (GM)
- Toscana Life Sciences (IT)
- University College London (GB)
- Charité - Universitätsmedizin Berlin (DE)
- University of Sheffield (GB)
Publication Details
- Journal
- Nature Medicine
- Published
- 2025-08-08
- DOI
- https://doi.org/10.1038/s41591-025-03868-4
- Citations
- 1
- Primary Topic
- Streptococcal Infections and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.88
Funders
- Wellcome