Evaluation of novel Streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein

M J Bauer; M M Georgousakis; T Vu; A Henningham; A Hofmann; M Rettel; L M Hafner; K S Sriprakash; David J McMillan

doi:10.1016/j.vaccine.2011.12.115

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Evaluation of novel Streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein

Journal article

Peer reviewed

Evaluation of novel Streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein

M J Bauer, M M Georgousakis, T Vu, A Henningham, A Hofmann, M Rettel, L M Hafner, K S Sriprakash and David J McMillan

Vaccine, Vol.30(12), pp.2197-2205

2012

DOI: https://doi.org/10.1016/j.vaccine.2011.12.115

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Abstract

streptococcus pyogenes

m-protein

vaccine

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.

Details

Title: Evaluation of novel Streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein
Authors: M J Bauer (Author) - Queensland Institute of Medical Research
M M Georgousakis (Author) - Queensland Institute of Medical Research
T Vu (Author) - Queensland Institute of Medical Research
A Henningham (Author) - University of Queensland
A Hofmann (Author) - Griffith University
M Rettel (Author) - University of Melbourne
L M Hafner (Author) - Queensland University of Technology
K S Sriprakash (Author) - Queensland Institute of Medical Research
David J McMillan (Author) - Queensland Institute of Medical Research
Publication details: Vaccine, Vol.30(12), pp.2197-2205
Publisher: Elsevier Ltd.
Date published: 2012
DOI: 10.1016/j.vaccine.2011.12.115
ISSN: 0264-410X
Organisation Unit: University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99450031302621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Immunology; Medicine, Research & Experimental

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