Shabir A Madhi1,2, Alane Izu1,2, Gaurav Kwatra1,2, Stephanie Jones1,2, Ziyaad Dangor1,2,3, Jeanette Wadula4, Andrew Moultrie1,2, Yasmin Adam5, Wenji Pu6, Ouzama Henry6, Carmen Briner1,2, Clare L Cutland1,2. 1. South African Medical Research Council: Vaccines and Infectious Diseases Analytical Research Unit (VIDA), University of the Witwatersrand, Faculty of Health Science Johannesburg, South Africa. 2. Department of Science/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Faculty of Health Science, Johannesburg, South Africa. 3. Department of Paediatrics, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. 4. National Health Laboratory Services, Department of Anatomical Pathology, School of Pathology, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa. 5. Department of Obstetrics and Gynecology, Chris Hani-Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. 6. GSK, Rockville, MD, USA.
Abstract
BACKGROUND: Licensure of a Group B streptococcus (GBS) polysaccharide-protein conjugate vaccine for protecting infants against invasive GBS disease (IGbsD) will likely need to be based on demonstrating vaccine safety in pregnant women, and benchmarking immunogenicity against a serological threshold associated with risk reduction of IGbsD. We investigated the association between naturally-derived GBS serotype-Ia and III IgG and risk reduction of IGbsD in infants' ≤90 days of age. METHODS: In a matched case-control study (ClinicalTrials.gov NCT02215226), IGbsD cases were identified from a cohort of 38,233 mother-newborn dyads. Mothers colonized vaginally with serotype-Ia or III at birth, and their healthy infants were eligible as matched controls. GBS serotype-specific anti-capsular IgG was measured on maternal and cord blood/infant sera by multiplex Luminex assay; and the IgG threshold associated with 90% risk reduction of IGbsD derived by estimating absolute disease risk. RESULTS: In infants born ≥34 weeks gestational age, cord-blood IgG geometric mean concentrations (GMC) were lower in cases than controls for serotype-Ia (0.05 vs. 0.50µg/ml; p=0.004) and III (0.20 vs. 0.38µg/ml; p=0.078). Cord-blood IgG concentration ≥1.04 and ≥1.53µg/ml were associated with 90% risk reduction of serotype-Ia and III IGbsD, respectively. The maternal sera IgG threshold associated with 90% risk reduction was ≥2.31 and ≥3.41µg/ml for serotype-Ia and III, respectively. CONCLUSIONS: The threshold associated with a reduced risk for serotype-Ia and III IGbsD identified on infant sera supports the case for licensure of a GBS polysaccharide-protein conjugate vaccine based on immunogenicity evaluation benchmarked against the defined thresholds.
BACKGROUND: Licensure of a Group B streptococcus (GBS) polysaccharide-protein conjugate vaccine for protecting infants against invasive GBS disease (IGbsD) will likely need to be based on demonstrating vaccine safety in pregnant women, and benchmarking immunogenicity against a serological threshold associated with risk reduction of IGbsD. We investigated the association between naturally-derived GBS serotype-Ia and III IgG and risk reduction of IGbsD in infants' ≤90 days of age. METHODS: In a matched case-control study (ClinicalTrials.gov NCT02215226), IGbsD cases were identified from a cohort of 38,233 mother-newborn dyads. Mothers colonized vaginally with serotype-Ia or III at birth, and their healthy infants were eligible as matched controls. GBS serotype-specific anti-capsular IgG was measured on maternal and cord blood/infant sera by multiplex Luminex assay; and the IgG threshold associated with 90% risk reduction of IGbsD derived by estimating absolute disease risk. RESULTS: In infants born ≥34 weeks gestational age, cord-blood IgG geometric mean concentrations (GMC) were lower in cases than controls for serotype-Ia (0.05 vs. 0.50µg/ml; p=0.004) and III (0.20 vs. 0.38µg/ml; p=0.078). Cord-blood IgG concentration ≥1.04 and ≥1.53µg/ml were associated with 90% risk reduction of serotype-Ia and III IGbsD, respectively. The maternal sera IgG threshold associated with 90% risk reduction was ≥2.31 and ≥3.41µg/ml for serotype-Ia and III, respectively. CONCLUSIONS: The threshold associated with a reduced risk for serotype-Ia and III IGbsD identified on infant sera supports the case for licensure of a GBS polysaccharide-protein conjugate vaccine based on immunogenicity evaluation benchmarked against the defined thresholds.
Authors: Judith Absalon; Raphael Simon; David Radley; Peter C Giardina; Kenneth Koury; Kathrin U Jansen; Annaliesa S Anderson Journal: Hum Vaccin Immunother Date: 2022-03-03 Impact factor: 4.526
Authors: I L Haeusler; O Daniel; C Isitt; R Watts; L Cantrell; S Feng; M Cochet; M Salloum; S Ikram; E Hayter; S Lim; T Hall; S Athaide; C A Cosgrove; J S Tregoning; K Le Doare Journal: Clin Exp Immunol Date: 2022-08-19 Impact factor: 5.732