Multicomponent Vaccines against Group A Streptococcus Can Effectively Target Broad Disease Presentations

Area of Science:

• Microbiology
• Immunology
• Vaccinology

Background:

• Group A Streptococcus (GAS) is a significant human pathogen causing diverse diseases, including pharyngitis and invasive infections.
• Rheumatic heart disease (RHD) is a major autoimmune sequela of GAS, highlighting the urgent need for an effective vaccine.
• Currently, no licensed vaccine is available to prevent GAS infections and their complications.

Purpose of the Study:

• To investigate protein antigens as vaccine components for Group A Streptococcus (GAS) in individual and combination formulations.
• To evaluate and compare the potency and functional immunity generated by these vaccine candidates.
• To assess the adequacy of opsonophagocytosis assays (OPA) for evaluating vaccine protection against GAS.

Main Methods:

• Antibody responses were analyzed in pooled human IgG (IVIG) and in mice immunized subcutaneously with individual or combination antigen formulations.
• Immune responses, including IgG titers and functional immunity (e.g., blocking assays), were measured.
• GAS killing activity was assessed using opsonophagocytosis assays (OPA) with immune sera.

Main Results:

• Antibodies against all tested components were detected in human IVIG and generated in immunized mice.
• Combination immunizations showed varied effects on IgG responses, increasing for Cpa and Mac-1 (IdeS) but decreasing for SpyCEP.
• OPA demonstrated GAS killing with M protein and combination group sera, while specific antigen assays confirmed functional immunity against SpyCEP and Mac-1. Blocking of Cpa binding activity was not achieved.

Conclusions:

• Combination immunizations can broaden coverage of GAS virulence factors but may modulate immune responses.
• OPA alone is insufficient for evaluating vaccine protection, especially against immune evasion factors and for preventing colonization leading to pharyngitis.
• Further research is needed to optimize vaccine strategies targeting GAS, considering both immune response modulation and comprehensive efficacy assessment.