Keeley Alexander J, Camara Fatoumata E, Armitage Edwin P, de Crombrugghe Gabrielle, Sillah Jainaba, Fofana Modou Lamin, Rollinson Victoria, Senghore Elina, Jammeh Musukoi, Whitcombe Alana L, Bittaye Amat, Ceesay Haddy, Ceesay Isatou, Samateh Bunja, Manneh Muhammed, Carducci Martina, Rovetini Luca, Boero Elena, Massai Luisa, Sanyang Lady Chilel, Camara Ousman, Cessay Ebrima E, Iturriza Miren, Moriel Danilo Gomes, Kucharski Adam, Smeesters Pierre R, Botteaux Anne, Jagne Ya Jankey, Moreland Nicole J, Clarke Ed, Kampmann Beate, Marks Michael, Rossi Omar, Salje Henrik, Turner Claire E, de Silva Thushan I
Vaccines and Immunity Theme, MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia.
Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK.
Nat Med. 2025 Aug 8. doi: 10.1038/s41591-025-03868-4.
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.
化脓性链球菌每年导致50万人死亡，在低收入地区，许多死亡是由风湿性心脏病引起的。对化脓性链球菌天然保护性免疫的了解有限，这阻碍了疫苗的研发。在此，我们描述了冈比亚从出生到整个生命过程中针对保守疫苗抗原和血清型特异性M蛋白的血清学特征的演变。随着出生后胎盘转移的IgG逐渐减少，23%的婴儿在出生后的第一年出现了新接触的血清学证据。在经培养确诊的化脓性链球菌感染事件后，2岁以下儿童在咽部和皮肤疾病以及两个部位的无症状携带后，IgG升高最为明显。针对保守疫苗抗原的较高IgG水平与功能活性相关，并且在调整年龄和抗M蛋白IgG水平后，与预防经培养确诊的事件相关。据我们所知，我们的数据首次提供了人类针对保守疫苗候选抗原的体液免疫相关保护的证据。
