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  • Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models

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    Rivera-HernandezPUB2227.pdf (1.060Mb)
    Author(s)
    Rivera-Hernandez, Tania
    Pandey, Manisha
    Henningham, Anna
    Cole, Jason
    Choudhury, Biswa
    Cork, Amanda J
    Gillen, Christine M
    Ghaffar, Khairunnisa Abdul
    West, Nicholas P
    Silvestri, Guido
    Good, Michael F
    Moyle, Peter M
    Toth, Istvan
    Nizet, Victor
    Batzloff, Michael R
    Walker, Mark J
    Griffith University Author(s)
    Batzloff, Michael R.
    Pandey, Manisha
    Good, Michael F.
    Rivera-Hernandez, Tania
    West, Nic P.
    Year published
    2016
    Metadata
    Show full item record
    Abstract
    Group A Streptococcus (GAS) is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i) streptolysin O (SLO), interleukin 8 (IL-8) protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP]), group A streptococcal C5a peptidase (SCPA), arginine deiminase (ADI), and trigger factor (TF); (ii) the conserved M-protein-derived ...
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    Group A Streptococcus (GAS) is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i) streptolysin O (SLO), interleukin 8 (IL-8) protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP]), group A streptococcal C5a peptidase (SCPA), arginine deiminase (ADI), and trigger factor (TF); (ii) the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii) group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a “gold standard” for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model.
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    Journal Title
    mBio
    Volume
    7
    Issue
    3
    DOI
    https://doi.org/10.1128/mBio.00618-16
    Copyright Statement
    © 2016 Rivera-Hernandez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Subject
    Microbiology not elsewhere classified
    Microbiology
    Publication URI
    http://hdl.handle.net/10072/100373
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    • Journal articles

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