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Evaluation of novel Streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein.
- Source :
-
Vaccine [Vaccine] 2012 Mar 09; Vol. 30 (12), pp. 2197-205. Date of Electronic Publication: 2012 Jan 20. - Publication Year :
- 2012
-
Abstract
- A major challenge for Streptococcus pyogenes vaccine development is the identification of epitopes that confer protection from infection by multiple S. pyogenes M-types. Here we have identified and characterised the distribution of common variant sequences from individual repeat units of the C-repeat region (CRR) of M-proteins representing 77 different M-types. Three polyvalent fusion vaccine candidates (SV1, SV2 and SV3) incorporating the most common variants were subsequently expressed and purified, and demonstrated to be alpha-helical by Circular Dichroism (CD), a secondary conformational characteristic of the CRR in the M-protein. Antibodies raised against each of these constructs recognise M-proteins that vary in their CRR, and bind to the surface of multiple S. pyogenes isolates. Antibodies raised against SV1, containing five variant sequences, also kill heterologous S. pyogenes isolates in in vitro bactericidal assays. Further structural characterisation of this construct demonstrated the conformation of SV1 was stable at different pHs, and thermal unfolding of SV1 is a reversible process. Our findings demonstrate that linkage of multiple variant sequences into a single recombinant construct overcomes the need to embed the variant sequences in foreign helix promoting flanking sequences for conformational stability, and demonstrates the viability of the polyvalent candidates as global S. pyogenes vaccine candidates.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antibodies, Bacterial blood
Antigens, Bacterial chemistry
Antigens, Bacterial genetics
Bacterial Outer Membrane Proteins chemistry
Bacterial Outer Membrane Proteins genetics
Blood Bactericidal Activity
Carrier Proteins chemistry
Carrier Proteins genetics
Circular Dichroism
Conserved Sequence
Epitopes genetics
Female
Mice
Microbial Viability drug effects
Protein Conformation
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins immunology
Repetitive Sequences, Amino Acid genetics
Repetitive Sequences, Amino Acid immunology
Streptococcal Vaccines genetics
Streptococcus pyogenes genetics
Vaccines, Synthetic genetics
Vaccines, Synthetic immunology
Antigens, Bacterial immunology
Bacterial Outer Membrane Proteins immunology
Carrier Proteins immunology
Epitopes immunology
Streptococcal Vaccines administration & dosage
Streptococcal Vaccines immunology
Streptococcus pyogenes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2518
- Volume :
- 30
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Vaccine
- Publication Type :
- Academic Journal
- Accession number :
- 22265945
- Full Text :
- https://doi.org/10.1016/j.vaccine.2011.12.115