Structural optimisation of a conformational epitope improves antigenicity when expressed as a recombinant fusion protein

M M Georgousakis; A Hofmann; M R Batzloff; David J McMillan; K S Sriprakash

doi:10.1016/j.vaccine.2009.08.049

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Structural optimisation of a conformational epitope improves antigenicity when expressed as a recombinant fusion protein

Journal article

Peer reviewed

Structural optimisation of a conformational epitope improves antigenicity when expressed as a recombinant fusion protein

M M Georgousakis, A Hofmann, M R Batzloff, David J McMillan and K S Sriprakash

Vaccine, Vol.27(48), pp.6799-6806

2009

DOI: https://doi.org/10.1016/j.vaccine.2009.08.049

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Abstract

streptococcus pyogenes

α-helix

fusion protein

peptide

vaccine

A conformationally restricted B cell epitope has been identified as a potential safe vaccine candidate from the major group A streptococcal virulence factor, the M protein. To maintain α-helical secondary structure, the minimal epitope is flanked with heterologous sequences to produce the chimeric vaccine candidate called J14. As a strategy toward developing an affordable multivalent GAS vaccine, we have expressed J14 recombinantly with a second GAS protective antigen H12 (rJ14H12). When administered to mice sub-cutaneously, the fusion protein stimulated a strong serum IgG response to the H12 component, but J14 was poorly immunogenic. To increase the immunogenicity of J14 when expressed with the model fusion partner, amino acid modifications were made to the initial recombinant J14 construct to produce rJJo. These changes stabilised the α-helical conformation of the recombinant antigen as assessed by circular dichroism. Mice immunised with rJJoH12, the fusion protein incorporating JJo, effectively stimulated a humoral response to both of the included antigens. These data support the feasibility of developing a multivalent vaccine incorporating the conformationally restricted protective antigen J14.

Details

Title: Structural optimisation of a conformational epitope improves antigenicity when expressed as a recombinant fusion protein
Authors: M M Georgousakis (Author) - Queensland Institute of Medical Research
A Hofmann (Author) - Griffith University
M R Batzloff (Author) - Griffith University
David J McMillan (Author) - Queensland Institute of Medical Research
K S Sriprakash (Author) - Griffith University
Publication details: Vaccine, Vol.27(48), pp.6799-6806
Publisher: Elsevier Ltd.
Date published: 2009
DOI: 10.1016/j.vaccine.2009.08.049
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: 99450221602621
Output Type: Journal article

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Web Of Science research areas: Immunology; Medicine, Research & Experimental

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