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Opsono-Adherence Assay to Evaluate Functional Antibodies in Vaccine Development Against Bacillus anthracis and Other Encapsulated Pathogens
Published on: May 19, 2020
Immunization with Staphylococcus aureus lysate incorporated into microspheres
C N O'Brien1, A J Guidry, L W Douglass
1Immunology and Disease Resistance Laboratory, USDA, Beltsville, MD 20705, USA. cobrien@anri.barc.usda.gov
Abstract:
Antibiotics are of limited value against Staphylococcus aureus due to development of resistant strains, scar tissue formation, and blockage of ducts due to inflammation. Though macrophages are the predominant cell type in the mammary gland, they are primarily scavenger cells and are not effective against bacteria entering the gland. Neutrophil phagocytosis is the bovine's primary defense against S. aureus mastitis. Attempts to develop vaccines that enhance neutrophil phagocytosis by stimulating production of opsonizing antibodies to S. aureus have met with limited success because of the low immunogenicity of the exopolysaccharide capsule surrounding S. aureus. Staphylococcus aureus can also adhere to and penetrate epithelial tissue. This study was conducted to determine whether lysates of S. aureus encapsulated in biodegradable microspheres would increase the production of opsonizing antibodies to capsule and block adherence. Four groups of four cows each were injected with 1 ml of the respective treatment in the area of the supramammary lymph node and 1 ml in the hip muscle. The treatments were: lysate in NaCl, lysate in Freund's incomplete adjuvant (FICA), lysate in microspheres in NaCl, and lysate in microspheres in FICA. Antigen in microspheres produced a similar antibody response to antigen emulsified in FICA, but to a lesser magnitude. Antigen in microspheres produced antibodies that were more opsonic for neutrophils at 20 and 52 wk postimmunization and inhibited S. aureus adherence to mammary epithelium. Ability to control antigen release and presentation, and the benefit of a single injection for long-term immunity using microspheres warrants additional studies.
Insights
Biodegradable microspheres carrying Staphylococcus aureus lysate show promise for enhancing bovine immunity against mastitis. This approach boosts opsonizing antibodies and inhibits bacterial adherence, offering a potential new strategy for controlling S. aureus infections.
Area of Science:
- Veterinary Immunology
- Bacterial Pathogenesis
- Vaccine Technology
Background:
- Antibiotic resistance and scar tissue limit treatment efficacy for Staphylococcus aureus (S. aureus) mastitis.
- Bovine neutrophils are crucial for combating S. aureus, but vaccines enhancing their function have shown limited success due to the bacteria's capsule.
- S. aureus can adhere to and penetrate mammary epithelial tissue, complicating infection control.
Purpose of the Study:
- To investigate if S. aureus lysate encapsulated in biodegradable microspheres can enhance opsonizing antibody production against the bacterial capsule.
- To determine if this microsphere-based approach can inhibit S. aureus adherence to mammary epithelium.
Main Methods:
- Four groups of cows were immunized with S. aureus lysate formulated in NaCl, Freund's incomplete adjuvant (FICA), microspheres in NaCl, or microspheres in FICA.
- Injections were administered in the supramammary lymph node and hip muscle.
- Antibody response, neutrophil opsonization, and bacterial adherence inhibition were assessed post-immunization.
Main Results:
- Microsphere encapsulation yielded an antibody response comparable in type to FICA but of lesser magnitude.
- Antibodies generated by microsphere immunization were more opsonic for neutrophils at 20 and 52 weeks post-immunization.
- The microsphere formulation effectively inhibited S. aureus adherence to mammary epithelium.
Conclusions:
- Biodegradable microspheres offer controlled antigen release and presentation, potentially enabling long-term immunity with a single injection.
- This technology warrants further investigation as a novel strategy to improve bovine mastitis control against S. aureus.
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