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MBio. 2016 Jun 14;7(3). pii: e00618-16. doi: 10.1128/mBio.00618-16.

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

Author information

  • 1Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland, Australia.
  • 2Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, Queensland, Australia.
  • 3University of California, San Diego, San Diego, California, USA.
  • 4Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
  • 5Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland, Australia School of Pharmacy, The University of Queensland, St. Lucia, Queensland, Australia.
  • 6Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland, Australia mark.walker@uq.edu.au.

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 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.

IMPORTANCE:

This set of experiments demonstrates the inherent variability of mouse models for the characterization of GAS vaccine candidate protective efficacy. Such variability poses an important challenge for GAS vaccine development, as advancement of candidates to human clinical trials requires strong evidence of efficacy. This study highlights the need for an open discussion within the field regarding standardization of animal models for GAS vaccine development.

PMID:
27302756
PMCID:
PMC4916377
DOI:
10.1128/mBio.00618-16
[PubMed - in process]
Free PMC Article
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