Comparative in silico analysis of two vaccine candidates for group A streptococcus predicts that they both may have similar safety profiles

M S Shaila; R Nayak; S S Prakash; M M Georgousakis; E Brandt; David J McMillan; M R Batzloff; S Pruksakorn; M F Good; K S Sriprakash

doi:10.1016/j.vaccine.2007.01.079

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Comparative in silico analysis of two vaccine candidates for group A streptococcus predicts that they both may have similar safety profiles

Journal article

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Comparative in silico analysis of two vaccine candidates for group A streptococcus predicts that they both may have similar safety profiles

M S Shaila, R Nayak, S S Prakash, M M Georgousakis, E Brandt, David J McMillan, M R Batzloff, S Pruksakorn, M F Good and K S Sriprakash

Vaccine, Vol.25(18), pp.3567-3573

2007

DOI: https://doi.org/10.1016/j.vaccine.2007.01.079

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Abstract

Biological Sciences

Agricultural and Veterinary Sciences

Medical and Health Sciences

streptococcus pyogenes

peptide

vaccine

safety

Concerns of immune cross-reactivity, between epitopes of the group A streptococcal (GAS) M-proteins and host proteins have hindered the progress of an effective GAS vaccine. An ideal M-protein based subunit vaccine should not elicit heart tissue cross-reactive antibody responses and should not activate M-protein specific CD4+ T-cells. In the current study we used a bioinformatic and immunoinformatic approach to assess the safety of J8 and J14, chimeric vaccine constructs containing a GAS derived M-protein epitope embedded in flanking GCN4 region. We demonstrate that at the primary amino acid level J8 and J14 show very little homology to human proteins. ProPred, RANKPEP and HLABIND algorithms failed to predict significant binding between the M-protein specific regions of J8 and J14 and class II binding alleles. A single peptide was predicted to bind to HLA class I allele B_2705. This data was supported by cellular proliferation assays demonstrating few periferal blood mononuclear cells (PBMCs) from donors respond to J8 and J14. Reassuringly, there was no correlation between proliferation to these peptides, and proliferation to host proteins. This data suggests that J8 and J14 are unlikely to induce cross-reactive immune responses, and will be safe for use in humans.

Details

Title: Comparative in silico analysis of two vaccine candidates for group A streptococcus predicts that they both may have similar safety profiles
Authors: M S Shaila (Author) - Indian Institute of Science, India
R Nayak (Author) - Indian Institute of Science, India
S S Prakash (Author) - Indian Institute of Science, India
M M Georgousakis (Author) - Queensland Institute of Medical Research
E Brandt (Author) - Queensland Institute of Medical Research
David J McMillan (Author) - Queensland Institute of Medical Research
M R Batzloff (Author) - Queensland Institute of Medical Research
S Pruksakorn (Author) - Chiang Mai University, Thailand
M F Good (Author) - Queensland Institute of Medical Research
K S Sriprakash (Author) - Queensland Institute of Medical Research
Publication details: Vaccine, Vol.25(18), pp.3567-3573
Publisher: Elsevier Ltd.
Date published: 2007
DOI: 10.1016/j.vaccine.2007.01.079
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: 99450242502621
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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