Surface protein distribution in Group B Streptococcus isolates from South Africa and identifying vaccine targets through in silico analysis

Abstract

Group B Streptococcus (GBS) is a major cause of pneumonia, sepsis, and meningitis in infants younger than 3 months of age. Furthermore, GBS infection in pregnant women is associated with stillbirths and pre-term delivery. It also causes disease in immunocompromised adults and the elderly, but the highest incidence of the disease occurs in neonates and young infants. At this time, there are no licensed vaccines against GBS. Complete GBS genome sequencing has helped identify genetically conserved and immunogenic proteins, which could serve as vaccine immunogens. In this study, in silico reverse vaccinology method were used to evaluate the prevalence and conservation of GBS proteins in invasive and colonizing isolates from South African infants and women, respectively. Furthermore, this study aimed to predict potential GBS vaccine targets by evaluating metrics such as antigenicity, physico-chemical properties, subcellular localization, secondary and tertiary structures, and epitope prediction and conservation. A total of 648 invasive and 603 colonizing GBS isolate sequences were screened against a panel of 89 candidate GBS proteins. Ten of the 89 proteins were highly genetically conserved in invasive and colonizing GBS isolates, nine of which were computationally inferred proteins (gbs2106, SAN_1577, SAN_0356, SAN_1808, SAN_1685, SAN_0413, SAN_0990, SAN_1040, SAN_0226) and one was the surface Immunogenic Protein (SIP). Additionally, the nine proteins were predicted to be more antigenic than the SIP protein (antigenicity score of > 0.6498), highlighting their potential as GBS vaccine antigen targets.

Keywords: Group B streptococcus; In silico; Maternal vaccination; Prevalence; Vaccine development.

Fig. 1

Heatmap illustrating the frequency of highly antigenic GBS surface proteins present in South African GBS clinical isolates and stratified according to disease phenotype: Infant invasive and non-invasive (Maternal Colonization) isolates. Heat map created using GraphPad Prism Version 7.0 (GraphPad Software Inc. California USA).

Fig. 2

The flowchart illustrates the systematic selection of two proteins; SIP and gbs2106 for 3D modelling and protein expression analysis using flow cytometry. These proteins were selected using bioinformatic tools and the selection criteria included; high protein frequency among GBS clinical isolates, high antigenicity, favourable vaccine characteristics and surface exposed B-cell epitopes.

Fig. 3

gbs2106 protein, shown in red, docked on to HLADRB1*15:01, shown in blue. The MHC-II epitope QVNSAIKAYRAQGLS is shown by the pink region. 3D model created using PyMOL.

Fig. 4

The bar charts illustrate the percentage of South African GBS clinical isolates that contain gbs2106 and SIP genes (shown by the black bars) determined using in silico analysis, and the percentage of isolates that express gbs2106 and SIP on their surface (shown by the grey bars) determined using flow cytometry.