Functional activity of maternal and cord antibodies elicited by an investigational group B Streptococcus trivalent glycoconjugate vaccine in pregnant women
Monica Fabbrini, Fabio Rigat, Giovanna Tuscano, Emiliano Chiarot, Gilbert Donders, Roland Devlieger, Sara Filippini, Elisabetta Frigimelica, Pietro Forte, Frederick Wittke, Scott A Halperin, Karen Slobod, Guido Grandi, Immaculada Margarit, Monica Fabbrini, Fabio Rigat, Giovanna Tuscano, Emiliano Chiarot, Gilbert Donders, Roland Devlieger, Sara Filippini, Elisabetta Frigimelica, Pietro Forte, Frederick Wittke, Scott A Halperin, Karen Slobod, Guido Grandi, Immaculada Margarit
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.
Keywords: Capsular polysaccharide; GBS; Immune responses; Neonatal infection.
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Source: PubMed