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Evaluating the Immune Response of a Nanoemulsion Adjuvant Vaccine Against Methicillin-Resistant Staphylococcus aureus (MRSA) Infection
Published on: September 1, 2023
Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice
Hwan Keun Kim1, Alice G Cheng, Hye-Young Kim
1Department of Microbiology, University of Chicago, Chicago, IL 60637.
Abstract:
The current epidemic of hospital- and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has caused significant human morbidity, but a protective vaccine is not yet available. Prior infection with S. aureus is not associated with protective immunity. This phenomenon involves staphylococcal protein A (SpA), an S. aureus surface molecule that binds to Fcgamma of immunoglobulin (Ig) and to the Fab portion of V(H)3-type B cell receptors, thereby interfering with opsonophagocytic clearance of the pathogen and ablating adaptive immune responses. We show that mutation of each of the five Ig-binding domains of SpA with amino acid substitutions abolished the ability of the resulting variant SpA(KKAA) to bind Fcgamma or Fab V(H)3 and promote B cell apoptosis. Immunization of mice with SpA(KKAA) raised antibodies that blocked the virulence of staphylococci, promoted opsonophagocytic clearance, and protected mice against challenge with highly virulent MRSA strains. Furthermore, SpA(KKAA) immunization enabled MRSA-challenged mice to mount antibody responses to many different staphylococcal antigens.
Insights
A mutated staphylococcal protein A (SpA) variant lacking immune-binding capabilities was developed. Immunization with this SpA variant protected mice against methicillin-resistant Staphylococcus aureus (MRSA) infections.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Hospital- and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections cause significant morbidity.
- No protective vaccine is currently available, and prior infection does not confer immunity.
- Staphylococcal protein A (SpA) interferes with immune responses by binding immunoglobulin (Ig) and B cell receptors.
Purpose of the Study:
- To investigate the role of SpA in immune evasion.
- To develop a potential vaccine candidate targeting SpA.
Main Methods:
- Mutagenesis of SpA's Ig-binding domains to create the SpA(KKAA) variant.
- Immunization of mice with SpA(KKAA).
- Assessment of immune responses and protection against MRSA challenge.
Main Results:
- SpA(KKAA) variants lost the ability to bind Fcgamma or Fab V(H)3 and induce B cell apoptosis.
- Immunization with SpA(KKAA) generated antibodies that blocked staphylococcal virulence.
- SpA(KKAA) immunization promoted opsonophagocytic clearance and protected mice against virulent MRSA strains.
- Vaccinated mice mounted antibody responses to multiple staphylococcal antigens.
Conclusions:
- Targeting SpA's immune-evasive functions is a promising strategy for MRSA vaccine development.
- The SpA(KKAA) variant represents a potential vaccine candidate for preventing MRSA infections.
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