title: Preclinical immunogenicity and safety of a Group A streptococcal M protein-based vaccine candidate.
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.
authors.affiliation: a Institute for Glycomics, Gold Coast Campus, Griffith University , Queensland , Australia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Batzloff
authors.affiliation: b Infectious Diseases and Immunopathogenesis Research Group , Australian Institute of Tropical Health and Medicine, James Cook University , Queensland , Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Fane
authors.affiliation: b Infectious Diseases and Immunopathogenesis Research Group , Australian Institute of Tropical Health and Medicine, James Cook University , Queensland , Australia.
authors.forename: Davina
authors.initials: D
authors.lastname: Gorton
authors.affiliation: a Institute for Glycomics, Gold Coast Campus, Griffith University , Queensland , Australia.
authors.forename: Manisha
authors.initials: M
authors.lastname: Pandey
authors.affiliation: a Institute for Glycomics, Gold Coast Campus, Griffith University , Queensland , Australia.
authors.forename: Tania
authors.initials: T
authors.lastname: Rivera-Hernandez
authors.affiliation: a Institute for Glycomics, Gold Coast Campus, Griffith University , Queensland , Australia.
authors.forename: Ainslie
authors.initials: A
authors.lastname: Calcutt
authors.affiliation: a Institute for Glycomics, Gold Coast Campus, Griffith University , Queensland , Australia.
authors.forename: Grace
authors.initials: G
authors.lastname: Yeung
authors.affiliation: a Institute for Glycomics, Gold Coast Campus, Griffith University , Queensland , Australia.
authors.forename: Jon
authors.initials: J
authors.lastname: Hartas
authors.affiliation: b Infectious Diseases and Immunopathogenesis Research Group , Australian Institute of Tropical Health and Medicine, James Cook University , Queensland , Australia.
authors.forename: Linda
authors.initials: L
authors.lastname: Johnson
authors.affiliation: b Infectious Diseases and Immunopathogenesis Research Group , Australian Institute of Tropical Health and Medicine, James Cook University , Queensland , Australia.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Rush
authors.affiliation: c QIMR Berghofer Medical Research Institute , Herston , Queensland , Australia.
authors.forename: James
authors.initials: J
authors.lastname: McCarthy
authors.affiliation: b Infectious Diseases and Immunopathogenesis Research Group , Australian Institute of Tropical Health and Medicine, James Cook University , Queensland , Australia.
authors.forename: Natkunam
authors.initials: N
authors.lastname: Ketheesan
authors.affiliation: a Institute for Glycomics, Gold Coast Campus, Griffith University , Queensland , Australia.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D051379:Mice; D011817:Rabbits; D011917:Rats, Inbred Lew; D013290:Streptococcal Infections / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D022541:Streptococcal Vaccines; D022223:Vaccines, Subunit; C014689:streptococcal M protein
keywords: M-protein; peptide; rheumatic fever; rheumatic heart disease; streptococcus pyogenes; vaccine