• Shabir A Madhi, Annaliesa S Anderson, Judith Absalon, David Radley, Raphael Simon, Babalwa Jongihlati, Renate Strehlau, Anika M van Niekerk, Alane Izu, Niree Naidoo, Gaurav Kwatra, Yogandree Ramsamy, Mohamed Said, Stephanie Jones, Lisa Jose, Lee Fairlie, Shaun L Barnabas, Ryan Newton, Samantha Munson, Zahra Jefferies, Danka Pavliakova, Natalie C Silmon de Monerri, Emily Gomme, John L Perez, Daniel A Scott, William C Gruber, and Kathrin U Jansen.
• 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): 215227215-227.

BackgroundNatural 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.MethodsIn 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.ResultsNaturally 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.ConclusionsGBS6 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.).Copyright © 2023 Massachusetts Medical Society.

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