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). e0156639. pp. 1-17.

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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.

Item ID: 44731
Item Type: Article (Research - C1)
ISSN: 1932-6203
Keywords: Streptococcus pyogenes, vaccine
Additional Information:

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.

https://creativecommons.org/licenses/by/4.0/

Funders: National Health and Medical Research Council (NHMRC) Australia, National Heart Foundation (NHF)
Date Deposited: 25 Jul 2016 03:51
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110801 Medical Bacteriology @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 50%
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