Group A Streptococcus infections of the nasopharynx cause significant disease burden and can disseminate from the mucosa leading to life-threatening diseases such as invasive disease and autoimmune sequelae. Development of an efficacious vaccine could provide immunity against GAS disease in humans. The paucity of late-stage human vaccine trials to prevent GAS infections presents a significant hurdle in determining efficacy, safety and correlates of protection for candidate human vaccines.
Utilizing a non-human primate (NHP) model of GAS pharyngitis in combination with intramuscular immunization with candidate recombinant protein GAS antigen formulation Combo#5 mixed with different adjuvants offers a preclinical opportunity to delineate immune parameters associated with protection from infection and disease.
Immunization with recombinant Combo#5 and experimental squalene-in-water emulsion adjuvant SMQ, but not Combo#5-Alum, lead to a significant reduction in pharyngeal GAS burden comparable to immunization with M1-Alum, and showed no vaccine safety concerns. Serology of T helper cytokine profiles was monitored with LEGENDplex and high-dimensional multi-color flow cytometry of peripheral blood mononuclear cells was performed over the course of immunization and throughout pharyngeal challenge with GAS M1 strain 5448. Protection from bacterial colonisation was associated with generation of antigen-specific CD4+ T cells with a Th1/2/17 phenotype using a multiplexed activation-induced marker (AIM) assay and was associated with a balance of peripheral Th cytokine secretion. Taken together these data reveal an important role for recombinant Combo#5-specific CD4+ T and B cell responses and demonstrates a significant step towards understanding correlates of protection for non-M protein GAS vaccines.