Association between anti-capsular IgG levels at birth and risk of invasive group B streptococcus disease in Finnish newborns: a retrospective case-control study

Annika Saukkoriipi; Natalie C Silmon de Monerri; Maija Toropainen; Laura Lindholm; Riitta Veijola; Jorma Toppari; Mikael Knip; David Radley; Emily Gomme; Babalwa Jongihlati; Annaliesa S Anderson; Arto A Palmu; Raphael Simon

doi:10.1016/S2666-5247(24)00038-7

Association between anti-capsular IgG levels at birth and risk of invasive group B streptococcus disease in Finnish newborns: a retrospective case-control study

Lancet Microbe. 2024 Apr 25:S2666-5247(24)00038-7. doi: 10.1016/S2666-5247(24)00038-7. Online ahead of print.

Affiliations

¹ Finnish Institute for Health and Welfare, Oulu, Finland.
² Vaccine Research and Development, Pfizer, Pearl River, NY, USA.
³ Finnish Institute for Health and Welfare, Helsinki, Finland.
⁴ Department of Pediatrics, Research Unit of Clinical Medicine, Medical Research Center, University of Oulu, Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
⁵ Institute of Biomedicine, Research Centre for Integrated Physiology and Pharmacology, Centre for Population Health Research, University of Turku, Turku, Finland; Department of Pediatrics, Turku University Hospital, Turku, Finland.
⁶ Department of Pediatrics, Tampere University Hospital, Tampere, Finland; Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁷ Finnish Institute for Health and Welfare, Tampere, Finland.
⁸ Vaccine Research and Development, Pfizer, Pearl River, NY, USA. Electronic address: raphael.simon@pfizer.com.

PMID: 38679040
DOI: 10.1016/S2666-5247(24)00038-7

Abstract

Background: Group B streptococcus is a major cause of neonatal disease. Natural history studies have linked maternally transferred anti-group B streptococcus capsular polysaccharide antibodies with protection against infant group B streptococcus disease. Previous studies of capsular polysaccharide antibody concentration in European populations have used maternal (not infant) sera and a non-standardised assay. This study aimed to evaluate anti-capsular polysaccharide IgG concentrations associated with protection against invasive group B streptococcus disease in Finnish infants.

Methods: In this retrospective case-control study, we used cord sera from the Finnish DIPP study repository, which was obtained between Jan 1, 1995, and Dec 31, 2017. We included infants aged 6 months or younger with group B streptococcus infection (cases) and healthy infants (controls). We enrolled infants with invasive neonatal group B streptococcus (55 cases) and matched controls (229 controls) aged 6 months or younger after identification from Finnish health registers. We measured anti-capsular polysaccharide IgG (serotypes Ia-V) concentration using a standardised immunoassay and we estimated its relationship to disease risk using a Bayesian model. We used the derived risk-concentration curve to predict potential efficacy of six-valent group B streptococcus capsular polysaccharide vaccine (GBS6) based on previously reported immunogenicity data.

Findings: Most (32 [58%] of 55 cases) group B streptococcus cases were due to serotype III and anti-serotype III streptococcus capsular IgG concentrations were higher in serotype III-matched controls than in cases (p<0·001). 0·120-0·266 μg/mL serotype III-specific IgG was estimated to confer 75-90% risk reduction against serotype III disease. A universal risk-concentration curve, aggregating results across all six serotypes, yielded similar results. Application of this curve to GBS6 immunogenicity data predicted maternal immunisation to be more than 80% efficacious for prevention of infant group B streptococcus disease.

Interpretation: Higher neonatal anti-capsular polysaccharide serum IgG concentration at birth correlated with reduced risk of infant group B streptococcus disease in Finland. Based on these results, a maternal group B streptococcus capsular conjugate vaccine currently in development is predicted to be efficacious.

Funding: Pfizer.