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A Synthetic M Protein Peptide Synergizes with a CXC Chemokine Protease To Induce Vaccine-Mediated Protection against Virulent Streptococcal Pyoderma and Bacteremia

Manisha Pandey, Emma Langshaw, Jon Hartas, Alfred Lam, Michael R. Batzloff and Michael F. Good
J Immunol May 15, 2015, 1500157; DOI: https://doi.org/10.4049/jimmunol.1500157
Manisha Pandey
Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia; and
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Emma Langshaw
Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia; and
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Jon Hartas
Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia; and
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Alfred Lam
Griffith Medical School, Griffith University, Gold Coast, Queensland 4222, Australia
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Michael R. Batzloff
Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia; and
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Michael F. Good
Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia; and
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Abstract

Infections caused by Streptococcus pyogenes (group A Streptococcus [GAS]) are highly prevalent in the tropics, in developing countries, and in the Indigenous populations of developed countries. These infections and their sequelae are responsible for almost 500,000 lives lost prematurely each year. A synthetic peptide vaccine (J8-DT) from the conserved region of the M protein has shown efficacy against disease that follows i.p. inoculation of bacteria. By developing a murine model for infection that closely mimics human skin infection, we show that the vaccine can protect against pyoderma and subsequent bacteremia caused by multiple GAS strains, including strains endemic in Aboriginal communities in the Northern Territory of Australia. However, the vaccine was ineffective against a hypervirulent cluster of virulence responder/sensor mutant GAS strain; this correlated with the strain’s ability to degrade CXC chemokines, thereby preventing neutrophil chemotaxis. By combining J8-DT with an inactive form of the streptococcal CXC protease, S. pyogenes cell envelope proteinase, we developed a combination vaccine that is highly effective in blocking CXC chemokine degradation and permits opsonic Abs to kill the bacteria. Mice receiving the combination vaccine were strongly protected against pyoderma and bacteremia, as evidenced by a 100–1000-fold reduction in bacterial burden following challenge. To our knowledge, a vaccine requiring Abs to target two independent virulence factors of an organism is unique.

Footnotes

  • This work was supported by a grant from the National Heart Foundation of Australia (APP1044023), a National Health and Medical Research Council (Australia) Program Grant (APP1037304), and a National Health and Medical Research Council (Australia) fellowship grant (to M.F.G.).

  • The online version of this article contains supplemental material.

  • Received January 23, 2015.
  • Accepted April 19, 2015.
  • Copyright © 2015 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 200 (8)
The Journal of Immunology
Vol. 200, Issue 8
15 Apr 2018
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A Synthetic M Protein Peptide Synergizes with a CXC Chemokine Protease To Induce Vaccine-Mediated Protection against Virulent Streptococcal Pyoderma and Bacteremia
Manisha Pandey, Emma Langshaw, Jon Hartas, Alfred Lam, Michael R. Batzloff, Michael F. Good
The Journal of Immunology May 15, 2015, 1500157; DOI: 10.4049/jimmunol.1500157

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A Synthetic M Protein Peptide Synergizes with a CXC Chemokine Protease To Induce Vaccine-Mediated Protection against Virulent Streptococcal Pyoderma and Bacteremia
Manisha Pandey, Emma Langshaw, Jon Hartas, Alfred Lam, Michael R. Batzloff, Michael F. Good
The Journal of Immunology May 15, 2015, 1500157; DOI: 10.4049/jimmunol.1500157
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Print ISSN 0022-1767        Online ISSN 1550-6606