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Protein rib: a novel group B streptococcal cell surface protein that confers protective immunity and is expressed by
M Stålhammar-Carlemalm1, L Stenberg, G Lindahl
1Department of Medical Microbiology, University of Lund, Sweden.
Insights
A newly identified cell surface protein, Rib, is expressed by most type III group B Streptococcus strains and confers protective immunity. This discovery may lead to a new protein vaccine against this significant neonatal pathogen.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Group B Streptococcus (GBS) causes invasive neonatal infections, with type III strains being most prevalent.
- The GBS capsule is a key virulence factor, but surface proteins like alpha and beta are often absent in type III strains.
Purpose of the Study:
- To identify and characterize novel cell surface proteins of type III GBS that confer protective immunity.
- To evaluate the potential of protein Rib as a vaccine candidate against GBS infections.
Main Methods:
- Protein Rib was identified, purified, and characterized from a type III GBS strain.
- Antiserum against protein Rib was generated and tested for protective immunity in mouse models.
- Immunological and biochemical analyses were performed to compare protein Rib with known GBS proteins.
Main Results:
- Protein Rib is expressed on 31 of 33 type III GBS strains, but rarely on other serotypes.
- Antiserum to protein Rib provided protection against lethal GBS infection in mice.
- Protein Rib shares structural and functional similarities with the alpha protein, suggesting a protein family.
Conclusions:
- Protein Rib is a promising vaccine candidate for preventing GBS infections, particularly those caused by type III strains.
- The identification of protein Rib expands our understanding of GBS virulence and immunity.
Abstract:
The group B Streptococcus, an important cause of invasive infections in the neonate, is classified into four major serotypes (Ia, Ib, II, and III) based on the structure of the polysaccharide capsule. Since the capsule is a known virulence factor, it has been extensively studied, in particular in type III strains, which cause the majority of invasive infections. Two cell surface proteins, alpha and beta, have also been studied in detail since they confer protective immunity, but these proteins are usually not expressed by type III strains. We describe here a cell surface protein, designated protein Rib (resistance to proteases, immunity, group B), that confers protective immunity and is expressed by most strains of type III. Protein Rib was first identified as a distinct 95-kD protein in extracts of a type III strain, and was purified to homogeneity from that strain. Rabbit antiserum to protein Rib was used to demonstrate that it is expressed on the cell surface of 31 out of 33 type III strains, but only on 1 out of 25 strains representing the other three serotypes. Mouse protection tests showed that antiserum to protein Rib protects against lethal infection with three different strains expressing this antigen, including a strain representing a recently identified high virulence type III clone. Protein Rib is immunologically unrelated to the alpha and beta proteins, but shares several features with the alpha protein. Most importantly, the NH2-terminal amino acid sequences of the Rib and alpha proteins are identical at 6 out of 12 positions. In addition, both protein Rib and the alpha protein are relatively resistant to trypsin (and Rib is also resistant to pepsin) and both proteins vary greatly in size between different clinical isolates. Finally, both protein Rib and the alpha protein exhibit a regular ladderlike pattern in immunoblotting experiments, which may reflect a repetitive structure. Taken together, these data suggest that the Rib and alpha proteins are members of a family of proteins with related structure and function. Since protein Rib confers protective immunity, it may be valuable for the development of a protein vaccine against the group B Streptococcus, an encapsulated bacterium.