Systematic review of Group B Streptococcal capsular types, sequence types and surface proteins as potential vaccine candidates

Abstract

Background: 21 million pregnant women worldwide (18%) are estimated to carry Group B Streptococcus (GBS), which is a risk for invasive disease in newborns, pregnant women, and stillbirths. Adults ≥ 60 years or with underlying health conditions are also vulnerable to invasive GBS disease. We undertook systematic reviews on GBS organism characteristics including: capsular polysaccharide (serotype), sequence type (multi-locus sequence types (MLST)), and virulence proteins. We synthesised data by at-risk populations, to inform vaccine development.

Methods: We conducted systematic reviews and meta-analyses to estimate proportions of GBS serotypes for at risk populations: maternal colonisation, invasive disease in pregnant women, stillbirths, infants 0-90 days age, and older adults (≥60 years). We considered regional variation and time trends (2001-2018). For these at-risk population groups, we summarised reported MLST and surface proteins.

Results: Based on 198 studies (29247isolates), 93-99% of GBS isolates were serotypes Ia, Ib, II, III, IV and V. Regional variation is likely, but data gaps are apparent, even for maternal colonisation which has most data. Serotype III dominates for infant invasive disease (60%) and GBS-associated stillbirths (41%). ST17 accounted for a high proportion of infant invasive disease (41%; 95%CI: 35-47) and was found almost exclusively in serotype III strains, less present in maternal colonisation (9%; 95%CI:6-13),(4%; 95%CI:0-11) infant colonisation, and adult invasive disease (4%, 95%CI:2-6). Percentages of strains with at least one of alp 1, alp2/3, alpha C or Rib surface protein targets were 87% of maternal colonisation, 97% infant colonisation, 93% infant disease and 99% adult invasive disease. At least one of three pilus islands proteins were reported in all strains.

Discussion: A hexavalent vaccine (serotypes Ia, Ib, II, III, IV and V) might provide comprehensive cover for all at-risk populations. Surveillance of circulating, disease-causing target proteins is useful to inform vaccines not targeting capsular polysaccharide. Addressing data gaps especially by world region and some at-risk populations (notably stillbirths) is fundamental to evidence-based decision-making during vaccine design.

Keywords: Adult; Group B Streptococcus; Maternal; Multi locus sequence typing; Neonatal; Serotypes; Stillbirth; Vaccine; Whole genome sequencing.

Fig. 1

Data search and included studies on group B Streptococcus: A. serotypes for maternal colonisation, B. serotypes for infant invasive disease, C. serotypes for maternal invasive GBS disease, D. serotypes for GBS- associated stillbirth, E. serotypes for streptococcal invasive disease in the elderly, F. MLST data, and G. virulence proteins. * Papers from both protein and MLST searches were combined for analysis.

Fig. 1

Data search and included studies on group B Streptococcus: A. serotypes for maternal colonisation, B. serotypes for infant invasive disease, C. serotypes for maternal invasive GBS disease, D. serotypes for GBS- associated stillbirth, E. serotypes for streptococcal invasive disease in the elderly, F. MLST data, and G. virulence proteins. * Papers from both protein and MLST searches were combined for analysis.

Fig. 2

Characterisation methods used for description and investigation of GBS strains.

Fig. 3

A. Distribution worldwide of GBS serotypes by risk population group, B. distribution of GBS serotypes by regions from maternal colonisation isolates (n = 17427), C. distribution of GBS serotypes by regions from infant invasive disease and stillbirth isolates (n = 8974), D. distribution of GBS serotypes by regions from invasive disease in elderly population isolates (n = 2525). Results are of adjusted percentages. Size of pie charts correspond to number of isolates from each region. Scale of pie charts not the same between figures B, C and D.

Fig. 4

Time variation of GBS serotypes (adjusted percentages with confidence intervals) for maternal colonisation, early-onset GBS disease and late-onset GBS disease isolates for countries in the developed region and countries from all other regions.