Expanding strain coverage of a group A Streptococcus pilus-expressing Lactococcus lactis mucosal vaccine

Area of Science:

• Microbiology
• Immunology
• Vaccinology

Background:

• Group A Streptococcus (GAS) causes significant global morbidity and mortality, with limited intervention success and no licensed vaccine.
• GAS pili are crucial for bacterial adhesion, biofilm formation, and immune evasion, making them a key vaccine target.
• A mucosal vaccine strategy using Lactococcus lactis to express GAS pili is under development.

Purpose of the Study:

• To evaluate the immune response to a combination vaccine of seven Lactococcus lactis constructs expressing different GAS pilus variants.
• To assess the cross-reactivity and protective efficacy of this multi-strain vaccine in a murine model.

Main Methods:

• Immunization of mice with a combination of seven Lactococcus lactis strains, each expressing a distinct GAS pilus.
• Measurement of systemic (IgG) and mucosal (IgA) immune responses against GAS pilus proteins.
• Evaluation of protective efficacy in a murine nasopharyngeal colonization model.

Main Results:

• The combination vaccine induced specific IgG and IgA responses to GAS pilus proteins, comparable to single-construct vaccines.
• Cross-reactivity to pilus proteins from non-vaccine GAS strains was observed.
• Significant protective efficacy against homologous GAS strain colonization in the nasopharynx was demonstrated.

Conclusions:

• Pilus-expressing Lactococcus lactis represents a viable mucosal vaccine strategy for preventing upper respiratory tract GAS infections.
• The combination approach broadens strain coverage and demonstrates protective potential.
• Further development of this platform could lead to a much-needed vaccine against GAS.