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Published on: November 16, 2016
Expanding strain coverage of a group A Streptococcus pilus-expressing Lactococcus lactis mucosal vaccine
Adrina Hema J-Khemlani1, Devaki Pilapitiya1, Catherine Jia-Yun Tsai1,2
1Department of Molecular Medicine & Pathology, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Abstract:
Group A Streptococcus (GAS) is a human pathogenic bacterium that can trigger a wide range of diseases, including the autoimmune diseases acute rheumatic fever and rheumatic heart disease, causing major morbidity and mortality in many low- and middle-income countries. Primary intervention programs have had limited success thus far, and a licensed vaccine has yet to be developed. The pilus of GAS is known to be involved in host cell adhesion, biofilm formation and immune evasion. We have a mucosal vaccine in development that expresses the pilus of GAS on the surface of the nonpathogenic bacterium Lactococcus lactis. To expand strain coverage, we combined seven L. lactis constructs, each expressing a different GAS pilus variant, and investigated the systemic and mucosal immune responses following immunization. Mice immunized with this combination showed specific immunoglobin G and immunoglobin A responses to the GAS pilus proteins of vaccine strains, at levels comparable to mice immunized with a single construct. Cross-reactivity to pilus proteins of nonvaccine strains was also evident. Furthermore, protective efficacy against a homologous strain of GAS in a murine nasopharyngeal colonization model was observed. Overall, this study provides further evidence for using pilus-expressing lactic acid bacteria as a vaccine to prevent upper respiratory tract GAS infections.
Insights
Developing a novel vaccine using Lactococcus lactis to express Group A Streptococcus (GAS) pili shows promise. This approach elicits immune responses and offers protection against GAS nasopharyngeal colonization.
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.
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