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

Area of Science:

• Vaccinology
• Microbiology
• Immunology

Background:

• Streptococcus pyogenes (group A Streptococcus, GAS) causes significant morbidity, including invasive diseases and post-infectious sequelae like rheumatic heart disease.
• A GAS vaccine could greatly reduce disease burden, but evaluating vaccine safety for post-infectious complications requires suitable models.
• Current limitations exist in animal models for assessing vaccine safety concerning post-infectious sequelae.

Purpose of the Study:

• To evaluate the safety and immunogenicity of the J8-DT vaccine formulation against Streptococcus pyogenes.
• To assess the efficacy of the J8-DT vaccine in preventing GAS-induced skin infections.
• To establish suitable animal models for vaccine safety and efficacy evaluation.

Main Methods:

• Utilized the Lewis Rat model to assess cardiac valvulitis as a measure of post-infectious complication safety.
• Conducted a parallel rabbit toxicology study to evaluate vaccine safety.
• Assessed vaccine immunogenicity and protective efficacy in a mouse model following GAS skin challenge.

Main Results:

• The J8-DT vaccine formulation did not induce abnormal pathology in Lewis Rats or rabbits.
• In mice, the J8-DT vaccine demonstrated high immunogenicity, inducing elevated antibody titers after two doses.
• Three doses of the J8-DT vaccine were required to confer protection against a GAS skin challenge in mice.

Conclusions:

• The J8-DT vaccine formulation is safe and does not induce adverse pathology in relevant animal models.
• While two doses of the J8-DT vaccine elicit high antibody titers in mice, three doses are necessary for protective immunity against skin infection.
• The Lewis Rat model shows promise for evaluating the safety of GAS vaccines concerning post-infectious complications.