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

• Main Authors: Tania Rivera-Hernandez, Manisha Pandey, Anna Henningham, Jason Cole, Biswa Choudhury, Amanda J. Cork, Christine M. Gillen, Khairunnisa Abdul Ghaffar, Nicholas P. West, Guido Silvestri, Michael F. Good, Peter M. Moyle, Istvan Toth, Victor Nizet, Michael R. Batzloff, Mark J. Walker
• Format: Article
• Language: English
• Published: American Society for Microbiology 2016-06-01
• Series: mBio
• Online Access: http://mbio.asm.org/cgi/content/full/7/3/e00618-16

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.