Journal article
Predicted Coverage and Immuno-Safety of a Recombinant C-Repeat Region Based Streptococcus pyogenes Vaccine Candidate
PLoS One, Vol.11(6), e0156639
2016
Abstract
The C-terminal region of the M-protein of Streptococcus pyogenes is a major target for vaccine development. The major feature is the C-repeat region, consisting of 35-42 amino acid repeat units that display high but not perfect identity. SV1 is a S. pyogenes vaccine candidate that incorporates five 14mer amino acid sequences (called J14i variants) from differing Crepeat units in a single recombinant construct. Here we show that the J14i variants chosen for inclusion in SV1 are the most common variants in a dataset of 176 unique M-proteins. Murine antibodies raised against SV1 were shown to bind to each of the J14i variants present in SV1, as well as variants not present in the vaccine. Antibodies raised to the individual J14i variants were also shown to bind to multiple but different combinations of J14i variants, supporting the underlying rationale for the design of SV1. A Lewis Rat Model of valvulitis was then used to assess the capacity of SV1 to induce deleterious immune response associated with rheumatic heart disease. In this model, both SV1 and the M5 positive control protein were immunogenic. Neither of these antibodies were cross-reactive with cardiac myosin or collagen. Splenic T cells from SV1/CFA and SV1/alum immunized rats did not proliferate in response to cardiac myosin or collagen. Subsequent histological examination of heart tissue showed that 4 of 5 mice from the M5/CFA group had valvulitis and inflammatory cell infiltration into valvular tissue, whereas mice immunised with SV1/CFA, SV1/alum showed no sign of valvulitis. These results suggest that SV1 is a safe vaccine candidate that will elicit antibodies that recognise the vast majority of circulating GAS M-types.
Details
- Title
- Predicted Coverage and Immuno-Safety of a Recombinant C-Repeat Region Based Streptococcus pyogenes Vaccine Candidate
- Authors
- Celia McNeilly (Author) - QIMR Berghofer Medical Research InstituteSamantha Cosh (Author) - QIMR Berghofer Medical Research InstituteTherese Vu (Author) - QIMR Berghofer Medical Research InstituteJemma Nicholls (Author) - University of the Sunshine Coast, QueenslandAnna Henningham (Author) - University of QueenslandAndreas Hofmann (Author) - Griffith UniversityAnne Fane (Author) - James Cook UniversityPierre R Smeesters (Author) - Université Libre de Bruxelles, BelgiumCatherine M Rush (Author) - James Cook UniversityLouise M Hafner (Author) - Queensland University of TechnologyN Ketheesan (Author) - James Cook UniversityKadaba S Sriprakash (Author) - QIMR Berghofer InstituteDavid J McMillan (Author) - University of the Sunshine Coast - Faculty of Science, Health, Education and Engineering
- Publication details
- PLoS One, Vol.11(6), e0156639; 18
- Publisher
- Public Library of Science
- Date published
- 2016
- DOI
- 10.1371/journal.pone.0156639
- ISSN
- 1932-6203
- Copyright note
- Copyright © 2016 McNeilly et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- 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
- 99450008602621
- Output Type
- Journal article
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