Preclinical immunogenicity and safety of a Group A streptococcal M protein-based vaccine candidate. Issue 12 (1st December 2016)

• Record Type: Journal Article
• Authors: Batzloff, Michael R.; Fane, Anne; Gorton, Davina; Pandey, Manisha; Rivera-Hernandez, Tania; Calcutt, Ainslie; Yeung, Grace; Hartas, Jon; Johnson, Linda; Rush, Catherine M.; McCarthy, James; Ketheesan, Natkunam; Good, Michael F.
• Is Part Of: Human vaccines & immunotherapeutics. Volume 12:Issue 12(2016)
• Page Start: 3089
• Page End: 3096
• Publication Date: 2016-12-01
• Subjects: M-protein -- peptide -- rheumatic fever -- rheumatic heart disease -- streptococcus pyogenes -- vaccine; Vaccines -- Periodicals; 615.372
• DOI: 10.1080/21645515.2016.1222999
• Languages: English
• ISSNs: 2164-5515

Abstract

ABSTRACT: Streptococcus pyogenes (group A streptococcus, GAS) causes a wide range of clinical manifestations ranging from mild self-limiting pyoderma to invasive diseases such as sepsis. Also of concern are the post-infectious immune-mediated diseases including rheumatic heart disease. The development of a vaccine against GAS would have a large health impact on populations at risk of these diseases. However, there is a lack of suitable models for the safety evaluation of vaccines with respect to post-infectious complications. We have utilized the Lewis Rat model for cardiac valvulitis to evaluate the safety of the J8-DT vaccine formulation in parallel with a rabbit toxicology study. These studies demonstrated that the vaccine did not induce abnormal pathology. We also show that in mice the vaccine is highly immunogenic but that 3 doses are required to induce protection from a GAS skin challenge even though 2 doses are sufficient to induce a high antibody titer.