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Conserved molecular chaperone PrsA stimulates protective immunity against group A Streptococcus
Chien-Yu Lai1, Jia-Xun Xie2, Meng-Chih Lai2
1Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
NPJ Vaccines
|February 26, 2024
Summary
Group A Streptococcus (GAS) vaccine development is challenging. However, PrsA1 and PrsA2 proteins are highly conserved and show promise as universal vaccine candidates, offering protection against GAS infection.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Group A Streptococcus (GAS) is a major human pathogen causing global health concerns.
- Developing a GAS vaccine is difficult due to diverse M-types and potential cross-reactive immune responses.
- PrsA1 and PrsA2, surface chaperone proteins, are crucial for GAS proteome homeostasis and virulence.
Purpose of the Study:
- To investigate the potential of PrsA1 and PrsA2 as vaccine candidates against GAS infection.
- To assess the conservation, immunogenicity, and protective efficacy of PrsA1 and PrsA2.
Main Methods:
- Analysis of PrsA1 and PrsA2 conservation across GAS isolates.
- Generation and characterization of anti-PrsA1/A2 antibodies for cross-reactivity and opsonophagocytic killing assays.
- Passive antibody transfer and active immunization studies in mouse models of GAS infection.
- Evaluation of immune responses, including Th1-associated IgG isotypes and complement activation.
Main Results:
- PrsA1 and PrsA2 proteins are highly conserved among GAS isolates with minimal amino acid variation.
- Anti-PrsA1/A2 antibodies did not cross-react with human heart proteins and enhanced neutrophil-mediated killing of GAS.
- Passive transfer of anti-PrsA1/A2 antibodies conferred protective immunity in mice.
- Immunization with CFA-adjuvanted PrsA1/A2 induced robust Th1 responses and provided ~70% protection against invasive GAS challenge.
Conclusions:
- PrsA1 and PrsA2 are highly conserved and safe targets for GAS vaccine development.
- Antibodies against PrsA1/A2 effectively neutralize GAS and confer protection.
- PrsA1 and PrsA2 represent promising candidates for a universal GAS vaccine.
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