Functional activity of maternal and cord antibodies elicited by an investigational group B Streptococcus trivalent glycoconjugate vaccine in pregnant women - 19/04/18

Doi : 10.1016/j.jinf.2018.01.006

Monica Fabbrini ^a,^{^{1
Monica Fabbrini and Fabio Rigat contributed equally to this manuscript.}}, Fabio Rigat ^a,^{^{1
Monica Fabbrini and Fabio Rigat contributed equally to this manuscript.},}^{^{2
Present address: GSK, Stevenage, UK.}}, Giovanna Tuscano ^a, Emiliano Chiarot ^a, Gilbert Donders ^b,^c,^d, Roland Devlieger ^e,^f,^g, Sara Filippini ^a, Elisabetta Frigimelica ^a, Pietro Forte ^a, Frederick Wittke ^a, Scott A. Halperin ^h,^i,^j,^k,^l, Karen Slobod ^m,^{^{3
Present address: Cambridge ID & Immunology Consulting, LLC, Cambridge, MA, USA.}}, Guido Grandi ^a,^{^{4
Present address: Centre for Integrative Biology, University of Trento, Trento, Italy.}}, Immaculada Margarit ^a,^*
^a GSK + Novartis Vaccines and Diagnostics, Siena, Italy
^b Femicare, Clinical Research for Women, Tienen, Belgium
^c Department of Obstetrics and Gynecology, Regional Hospital Heilig Hart, Tienen, Belgium
^d University Hospital Antwerpen, Antwerp, Belgium
^e Department of Obstetrics and Gynaecology, University Hospitals, KULeuven, Leuven, Belgium
^f Department of Growth and Regeneration, KULeuven, Leuven, Belgium
^g Department of Obstetrics, Fertility and General Gynaecology, Gasthuiszusters Antwerpen, Campus Wilrijk, Antwerp, Belgium
^h Canadian Center for Vaccinology, Dalhousie University, Halifax, Nova Scotia, Canada
ⁱ Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
^j Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
^k IWK Health Centre, Halifax, Nova Scotia, Canada
^l Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
^m GSK, Cambridge, MA, USA + Novartis Vaccines and Diagnostics, Cambridge, MA, USA

^*Corresponding author. GSK, Via Fiorentina 1, Siena, Italy.GSKVia Fiorentina 1SienaItaly

Highlights

•	A single dose of a GBS trivalent glycoconjugate vaccine elicited maternal and cord serum antibodies
•	Maternal and cord serum vaccine induced antibodies mediated phagocytic killing against GBS serotype Ia, Ib, and III isolates
•	IgG concentrations in maternal and cord sera correlated with their functional titers
•	IgG levels above 1 µg/mL were predictive of OPKA activity for all three serotypes
•	Passive administration of cord antibodies conferred dose-dependent protection against GBS infection to neonate mice

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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.

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Keywords : GBS, Neonatal infection, Capsular polysaccharide, Immune responses

Plan

Introduction

Materials and methods

Study design and participants

Determination of IgG concentrations against CPS Ia, Ib and III

OPKA for determination of antibody functional activity

In vivo passive protection model

Statistical analysis

Results

Antibody-mediated GBS opsono-phagocytic killing in maternal and cord sera

Association between OPKA functional activity and anti-capsular IgG

Prediction of mouse neonatal protection by anti-capsular IgG concentrations

Discussion

Funding

Authors contributions

Conflicts of interest

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Vol 76 - N° 5

P. 449-456 - mai 2018 Retour au numéro

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Functional activity of maternal and cord antibodies elicited by an investigational group B Streptococcus trivalent glycoconjugate vaccine in pregnant women - 19/04/18

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Abstract

Objectives

Methods

Results

Conclusions

Plan

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