Preclinical immunogenicity and safety of a Group A streptococcal M protein-based vaccine candidate

Journal Publication ResearchOnline@JCU
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.
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.

Journal

Human Vaccines & Immunotherapeutics

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Volume

12

ISBN/ISSN

2164-554X

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Issue

12

Pages Count

8

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Publisher

Landes Bioscience

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EISSN

N/A

DOI

10.1080/21645515.2016.1222999