Summary
Streptococcus agalactiae or group B Streptococcus (GBS) bacterial infection is a major health concern and a leading cause of sepsis and meningitis in infants, particularly in Africa.
A promising prevention for GBS infection in newborns is maternal immunization with a GBS vaccine. However, there is currently no vaccine for GBS available. Biovac is developing a traditional conjugate GBS vaccine using polysaccharides expressed on the surface of the GBS bacterium as antigens linked to tetanus toxoid as a carrier protein.
As part of WHO’s target product profile for a GBS vaccine, a one-dose vaccination regimen has been recommended. It remains to be ascertained whether a single dose of a traditional maternal GBS conjugate vaccine will elicit a sufficiently protective immune response in newborns. To enhance the response to a vaccine, we are proposing a novel vaccine design using GBS surface proteins conjugated to GBS polysaccharides. GBS proteins common to all serotypes have been identified as inducers of immune responses in infected individuals, making them potential candidates for novel GBS vaccines.
In this proof of concept project, we will conjugate a single GBS common protein to a single GBS polysaccharide with the aim to not only providing superior protection compared to traditional conjugate vaccines but to potentially provide protection against those serotypes not included in the vaccine. If successful, this will allow for the development of an affordable and cost-effective monovalent vaccine that protects against all GBS serotypes.
Project outcomes
In a collaborative effort between RMPRU, NIBSC and Biovac, a novel GBS glyco-protein conjugate using GBS polysaccharide linked to a GBS membrane protein as the carrier protein was generated. This conjugate will be further investigated towards a vaccine for maternal immunization to prevent GBS infections in newborns, while advancing African vaccine development and manufacturing capability.
RMPRU identified genes for several conserved GBS surface proteins and one of these proteins was cloned into vectors that were subsequently transformed into an Escherichia coli BL21 strain for protein expression 1-3. This strain was expanded into a working cell bank at Biovac.
To produce sufficient quantities of this surface protein, Biovac completed a proof of concept (POC) for antigen production and characterisation. To this end, approximately 1 g of protein was produced using a recombinant protein production process.
The physio-chemical characterisation of the novel GBS conserved protein was confirmed at NIBSC and Biovac utilising analytical tools that enables quantification of the protein as well as elucidating secondary and tertiary structure.
Biovac generated a novel GBS glyco-protein conjugate at small scale (25 mg) using GBS polysaccharide linked to a GBS membrane protein as the carrier protein.
The availability of these novel conjugate vaccines is a requirement for future studies to test the hypothesis that the GBS membrane protein-GBS polysaccharide conjugate is a superior vaccine candidate compared to traditional polysaccharide-Tetanus Toxoid conjugate vaccines. After successful generation of the GBS protein-CPS conjugates we are planning to assess their efficacy in producing an enhanced immune response in a mouse model compared to a conjugate utilizing a traditional carrier protein.
References:
- Sonwabile Dzanibe (2017), Natural Induced Antibodies Against Group B Streptococcus Surface Proteins and Capsular Polysaccharides; Department of Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of Witwatersrand.
- S. Dzanibe et al., (2016), Natural acquired group B Streptococcus capsular polysaccharide and surface protein antibodies in HIV-infected and HIV-uninfected children; Vaccine 34 (Issue 44), pages 5217-5224.
- S. Dzanibe et al., (2017), Reduced Transplacental Transfer of Group B Streptococcus Surface Protein Antibodies in HIV-infected Mother–Newborn Dyads; Journal of Infectious Diseases (215), pages 415-419.
- https://www.uniprot.org/uniprot/Q8E2L6