From the South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit (S.A.M., R. Strehlau, A.I., G.K., S.J., L.J.), the Department of Paediatrics and Child Health, Faculty of Health Sciences, Rahima Moosa Mother and Child Hospital (R. Strehlau), and Wits RHI, Faculty of Health Sciences, University of the Witwatersrand (L.F.), Johannesburg, the Division of Neonatal Medicine, School of Child and Adolescent Health, Faculty of Health Sciences, University of Cape Town, and Mowbray Maternity Hospital, Cape Town (A.M.N.), the Clinical Neonatology Unit, Prince Mshiyeni Memorial Hospital (N.N.), and the Department of Medical Microbiology, National Health Laboratory Services, Prince Mshiyeni Memorial Hospital and College of Health Sciences, University of KwaZulu-Natal (Y.R.), Durban, the University of Pretoria and the Tshwane Academic Division, National Health Laboratory Services, Pretoria (M.S.), and the Family Center for Research with Ubuntu, Department of Paediatrics and Child Health, Stellenbosch University, Stellenbosch (S.L.B.) - all in South Africa; and Vaccine Research and Development, Pfizer, Pearl River, NY (A.S.A., J.A., D.R., R. Simon, B.J., R.N., S.M., Z.J., D.P., N.C.S.M., E.G., J.L.P., D.A.S., W.C.G., K.U.J.).
N Engl J Med. 2023 Jul 20;389(3):215-227. doi: 10.1056/NEJMoa2116045.
BACKGROUND: Natural history studies have correlated serotype-specific anti-capsular polysaccharide (CPS) IgG in newborns with a reduced risk of group B streptococcal disease. A hexavalent CPS-cross-reactive material 197 glycoconjugate vaccine (GBS6) is being developed as a maternal vaccine to prevent invasive group B streptococcus in young infants. METHODS: In an ongoing phase 2, placebo-controlled trial involving pregnant women, we assessed the safety and immunogenicity of a single dose of various GBS6 formulations and analyzed maternally transferred anti-CPS antibodies. In a parallel seroepidemiologic study that was conducted in the same population, we assessed serotype-specific anti-CPS IgG concentrations that were associated with a reduced risk of invasive disease among newborns through 89 days of age to define putative protective thresholds. RESULTS: Naturally acquired anti-CPS IgG concentrations were associated with a reduced risk of disease among infants in the seroepidemiologic study. IgG thresholds that were determined to be associated with 75 to 95% reductions in the risk of disease were 0.184 to 0.827 μg per milliliter. No GBS6-associated safety signals were observed among the mothers or infants. The incidence of adverse events and of serious adverse events were similar across the trial groups for both mothers and infants; more local reactions were observed in the groups that received GBS6 containing aluminum phosphate. Among the infants, the most common serious adverse events were minor congenital anomalies (umbilical hernia and congenital dermal melanocytosis). GBS6 induced maternal antibody responses to all serotypes, with maternal-to-infant antibody ratios of approximately 0.4 to 1.3, depending on the dose. The percentage of infants with anti-CPS IgG concentrations above 0.184 μg per milliliter varied according to serotype and formulation, with 57 to 97% of the infants having a seroresponse to the most immunogenic formulation. CONCLUSIONS: GBS6 elicited anti-CPS antibodies against group B streptococcus in pregnant women that were transferred to infants at levels associated with a reduced risk of invasive group B streptococcal disease. (Funded by Pfizer and the Bill and Melinda Gates Foundation; C1091002 ClinicalTrials.gov number, NCT03765073.).
背景：自然病史研究表明，新生儿血清型特异性荚膜多糖（CPS）IgG 与降低 B 群链球菌疾病风险相关。一种六价 CPS 交叉反应性 197 糖缀合物疫苗（GBS6）正被开发为一种母体疫苗，以预防婴幼儿侵袭性 B 群链球菌。
方法：在一项正在进行的、涉及孕妇的 2 期、安慰剂对照试验中，我们评估了单剂不同 GBS6 制剂的安全性和免疫原性，并分析了母体转移的抗 CPS 抗体。在同一人群中进行的平行血清流行病学研究中，我们评估了与新生儿至 89 日龄侵袭性疾病风险降低相关的血清型特异性抗 CPS IgG 浓度，以确定潜在的保护阈值。
结果：血清流行病学研究中，自然获得的抗 CPS IgG 浓度与婴儿疾病风险降低相关。确定与疾病风险降低 75%至 95%相关的 IgG 阈值为 0.184 至 0.827μg/ml。母亲或婴儿均未观察到与 GBS6 相关的安全性信号。各组母亲和婴儿的不良事件和严重不良事件发生率相似；接受含磷酸铝 GBS6 的组中观察到更多的局部反应。在婴儿中，最常见的严重不良事件为轻微先天性畸形（脐疝和先天性皮肤黑色素细胞增多症）。GBS6 诱导母体针对所有血清型的抗体反应，母体-婴儿抗体比值约为 0.4 至 1.3，取决于剂量。根据血清型和制剂的不同，血清 CPS IgG 浓度高于 0.184μg/ml 的婴儿比例为 57%至 97%，其中最具免疫原性的制剂有 57%至 97%的婴儿产生血清反应。
结论：GBS6 在孕妇中诱导针对 B 群链球菌的抗 CPS 抗体，并以与降低侵袭性 B 群链球菌疾病风险相关的水平转移给婴儿。（由辉瑞和比尔及梅琳达·盖茨基金会资助；C1091002 ClinicalTrials.gov 编号，NCT03765073）。
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