Group B Streptococcus vaccine: state of the art

Abstract

Group B Streptococcus (GBS) is cause of neonatal invasive diseases as well as of severe infections in the elderly and immune-compromised patients. Despite significant advances in the prevention and treatment of neonatal disease, sepsis and meningitis caused by GBS still represent a significant public health care concern globally and additional prevention and therapeutic strategies against infection are highly desirable. The introduction of national recommended guidelines in several countries to screen pregnant women for GBS carriage and the use of antibiotics during delivery significantly reduced disease occurring within the first hours of life (early-onset disease), but it has had no effect on the late-onset diseases occurring after the first week and is not feasible in most countries. Availability of an effective vaccine against GBS would provide an effective means of controlling GBS disease. This review provides an overview of the burden of invasive disease caused by GBS in infants and adults, and highlights the strategies for the development of an effective vaccine against GBS infections.

Keywords: CPS-based conjugate vaccine; early-onset disease; group B Streptococcus; late-onset disease; protein-based vaccine.

Figure 1.

Genome-based and structural approaches applied to Group B Streptococcus (GBS) for antigen discovery and development. (a) Pan-genomic reverse vaccinology through multiple genome analysis has identified 4 potential new vaccine antigens among 312 putative surface/secreted proteins screened in an active maternal immunization/neonatal pup challenge model. Bioinformatic tools were used to analyse and compare the genome sequences of eight GBS strains in order to identify all potential vaccine candidates according to their topological features; selected open reading frames (ORFs) were amplified, cloned in expression vectors, purified and used to immunize mice; mice immune sera were analysed by fluorescence-activated cell sorting (FACS) to verify whether the antigens were expressed and surface-exposed; and finally, a mouse model was used to assess protective immunity of the antigens [Maione et al. 2005]. (b) Schematic representation of the three genomic pilus islands (PIs) identified in GBS. Each pilus contains two protective subunits (indicated by red circles) identified as novel vaccine candidates by genome-based approaches. Pili are high molecular weight polymers, visible by electron microscopy as long filamentous structures extending out from the bacterial surface [Rosini et al. 2006; Margarit et al. 2009]. (c) Antigen variability studies in large collection of clinical isolates representative of circulating strains causing diseases worldwide (selected through molecular epidemiology studies) allowed the design of a trivalent pilus-based vaccine potentially capable to confer broad serotype-independent protection [Margarit et al. 2009]. (d) Structural vaccinology, based on the atomic resolution of the structures of potential antigens, allowed the rational engineering of target epitopes to use as vaccine candidates to achieve a more comprehensive coverage against the major circulating species [Nuccitelli et al. 2011].