Predicted coverage and immuno-safety of a recombinant c-repeat region based Streptococcus pyogenes vaccine candidate

McNeilly, Celia, Cosh, Samantha, Vu, Therese, Nichols, Jemma, Henningham, Anna, Hofmann, Andreas, Fane, Anne, Smeesters, Pierre R., Rush, Catherine M., Hafner, Louise M., Ketheesan, Natkuman, Sriprakash, Kadaba S. and McMillan, David J. (2016) Predicted coverage and immuno-safety of a recombinant c-repeat region based Streptococcus pyogenes vaccine candidate. Plos One, 11 6: . doi:10.1371/journal.pone.0156639


Author McNeilly, Celia
Cosh, Samantha
Vu, Therese
Nichols, Jemma
Henningham, Anna
Hofmann, Andreas
Fane, Anne
Smeesters, Pierre R.
Rush, Catherine M.
Hafner, Louise M.
Ketheesan, Natkuman
Sriprakash, Kadaba S.
McMillan, David J.
Title Predicted coverage and immuno-safety of a recombinant c-repeat region based Streptococcus pyogenes vaccine candidate
Formatted title
Predicted coverage and immuno-safety of a recombinant c-repeat region based Streptococcus pyogenes vaccine candidate
Journal name Plos One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2016-06-16
Year available 2016
Sub-type Article (original research)
DOI 10.1371/journal.pone.0156639
Open Access Status DOI
Volume 11
Issue 6
Total pages 17
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2017
Language eng
Formatted 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 C-repeat 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.
Keyword Streptococcus pyogenes
Vaccine development
C-repeat region
SV1
J14i variants
GAS M-types
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
 
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