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. Anticapsular 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. Anticapsular IgG concentrations in maternal and cord sera were predictive of functional activity and in vivo protection in the mouse model.

Functional activity of maternal and cord antibodies elicited by an investigational group B Streptococcus trivalent glycoconjugate vaccine in pregnant women / Fabbrini, Monica; Rigat, Fabio; Tuscano, Giovanna; Chiarot, Emiliano; Donders, Gilbert; Devlieger, Roralnd; Filippini, Sara; Frigimelica, Elisabetta; Forte, Pietro; Wittke, Frederick; Halperin, Scott A; Slobod, Karen; Grandi, Guido; Margarit, Immaculada. - In: JOURNAL OF INFECTION. - ISSN 0163-4453. - 2018/76:5(2018), pp. 449-456. [10.1016/j.jinf.2018.01.006]

Functional activity of maternal and cord antibodies elicited by an investigational group B Streptococcus trivalent glycoconjugate vaccine in pregnant women.

Grandi, Guido;
2018-01-01

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. Anticapsular 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. Anticapsular IgG concentrations in maternal and cord sera were predictive of functional activity and in vivo protection in the mouse model.
2018
5
Fabbrini, Monica; Rigat, Fabio; Tuscano, Giovanna; Chiarot, Emiliano; Donders, Gilbert; Devlieger, Roralnd; Filippini, Sara; Frigimelica, Elisabetta; ...espandi
Functional activity of maternal and cord antibodies elicited by an investigational group B Streptococcus trivalent glycoconjugate vaccine in pregnant women / Fabbrini, Monica; Rigat, Fabio; Tuscano, Giovanna; Chiarot, Emiliano; Donders, Gilbert; Devlieger, Roralnd; Filippini, Sara; Frigimelica, Elisabetta; Forte, Pietro; Wittke, Frederick; Halperin, Scott A; Slobod, Karen; Grandi, Guido; Margarit, Immaculada. - In: JOURNAL OF INFECTION. - ISSN 0163-4453. - 2018/76:5(2018), pp. 449-456. [10.1016/j.jinf.2018.01.006]
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