Monica Fabbrini1, Fabio Rigat1, Giovanna Tuscano1, Emiliano Chiarot1, Gilbert Donders2, Roland Devlieger3, Sara Filippini1, Elisabetta Frigimelica1, Pietro Forte1, Frederick Wittke1, Scott A Halperin4, Karen Slobod5, Guido Grandi1, Immaculada Margarit6. 1. GSK + Novartis Vaccines and Diagnostics, Siena, Italy. 2. Femicare, Clinical Research for Women, Tienen, Belgium; Department of Obstetrics and Gynecology, Regional Hospital Heilig Hart, Tienen, Belgium; University Hospital Antwerpen, Antwerp, Belgium. 3. Department of Obstetrics and Gynaecology, University Hospitals, KULeuven, Leuven, Belgium; Department of Growth and Regeneration, KULeuven, Leuven, Belgium; Department of Obstetrics, Fertility and General Gynaecology, Gasthuiszusters Antwerpen, Campus Wilrijk, Antwerp, Belgium. 4. Canadian Center for Vaccinology, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada; IWK Health Centre, Halifax, Nova Scotia, Canada; Nova Scotia Health Authority, Halifax, Nova Scotia, Canada. 5. GSK, Cambridge, MA, USA + Novartis Vaccines and Diagnostics, Cambridge, MA, USA. 6. GSK + Novartis Vaccines and Diagnostics, Siena, Italy. Electronic address: immaculada.x.margarit-y-ros@gsk.com.
Abstract
OBJECTIVES: The main aim of this exploratory study was to evaluate functional activity of antibodies elicited by a maternal Group B Streptococcus (GBS) investigational vaccine composed of capsular polysaccharides Ia, Ib, and III conjugated to genetically detoxified Diphtheria toxin CRM197. The second objective was to investigate the relationship between serotype-specific IgG concentrations and functional activity in maternal and cord sera. METHODS: Maternal and cord sera collected at baseline and at delivery from vaccine and placebo recipients during a double-blind placebo-controlled Phase II study (www.clinicaltrials.gov, NCT01446289) were tested in an opsono-phagocytic bacterial killing assay. Cord sera from vaccine recipients were also passively transferred to newborn mice to investigate conferred protection against bacterial challenge. RESULTS:Antibody-mediated GBS phagocytic killing was significantly increased in maternal serum at delivery and in cord sera from the investigational vaccine group as compared to the placebo group. Anti-capsular IgG concentrations above 1 µg/mL mediated in vitro killing against GBS strains belonging to all three serotypes and IgG levels correlated with functional titers. Passively administered cord sera elicited a dose-dependent protective response against all GBS serotypes in the in vivo model. CONCLUSIONS: The maternal vaccine elicited functional antibodies that were placentally transferred. Anti-capsular IgG concentrations in maternal and cord sera were predictive of functional activity and in vivo protection in the mouse model.
RCT Entities:
OBJECTIVES: The main aim of this exploratory study was to evaluate functional activity of antibodies elicited by a maternal Group B Streptococcus (GBS) investigational vaccine composed of capsular polysaccharides Ia, Ib, and III conjugated to genetically detoxified Diphtheria toxin CRM197. The second objective was to investigate the relationship between serotype-specific IgG concentrations and functional activity in maternal and cord sera. METHODS: Maternal and cord sera collected at baseline and at delivery from vaccine and placebo recipients during a double-blind placebo-controlled Phase II study (www.clinicaltrials.gov, NCT01446289) were tested in an opsono-phagocytic bacterial killing assay. Cord sera from vaccine recipients were also passively transferred to newborn mice to investigate conferred protection against bacterial challenge. RESULTS: Antibody-mediated GBS phagocytic killing was significantly increased in maternal serum at delivery and in cord sera from the investigational vaccine group as compared to the placebo group. Anti-capsular IgG concentrations above 1 µg/mL mediated in vitro killing against GBS strains belonging to all three serotypes and IgG levels correlated with functional titers. Passively administered cord sera elicited a dose-dependent protective response against all GBS serotypes in the in vivo model. CONCLUSIONS: The maternal vaccine elicited functional antibodies that were placentally transferred. Anti-capsular IgG concentrations in maternal and cord sera were predictive of functional activity and in vivo protection in the mouse model.
Authors: Johan Vekemans; Jonathan Crofts; Carol J Baker; David Goldblatt; Paul T Heath; Shabir A Madhi; Kirsty Le Doare; Nick Andrews; Andrew J Pollard; Samir K Saha; Stephanie J Schrag; Peter G Smith; David C Kaslow Journal: Vaccine Date: 2019-04-25 Impact factor: 3.641
Authors: Bahaa Abu-Raya; Kirsten Maertens; Kathryn M Edwards; Saad B Omer; Janet A Englund; Katie L Flanagan; Matthew D Snape; Gayatri Amirthalingam; Elke Leuridan; Pierre Van Damme; Vana Papaevangelou; Odile Launay; Ron Dagan; Magda Campins; Anna Franca Cavaliere; Tiziana Frusca; Sofia Guidi; Miguel O'Ryan; Ulrich Heininger; Tina Tan; Ahmed R Alsuwaidi; Marco A Safadi; Luz M Vilca; Nasamon Wanlapakorn; Shabir A Madhi; Michelle L Giles; Roman Prymula; Shamez Ladhani; Federico Martinón-Torres; Litjen Tan; Lessandra Michelin; Giovanni Scambia; Nicola Principi; Susanna Esposito Journal: Front Immunol Date: 2020-06-24 Impact factor: 7.561