Lysibodies are IgG Fc fusions with lysin binding domains targeting Staphylococcus aureus wall carbohydrates for effective phagocytosis
Abstract
Antibiotic resistance is an ever-increasing problem; for certain pathogens, few treatment options remain. Vaccines and therapeutic antibodies represent important alternatives to antibiotics, yet despite extensive effort no approved vaccine is available for Staphylococcus aureus. Although wall carbohydrates are ideal immunotherapeutic targets due to their abundance and high level of conservation, their poor immunogenicity compared with conventional protein targets complicates the production of effective antibodies. The approach presented here fuses the high-affinity binding domains from bacteriophage lysins and autolysins that recognize specific cell wall carbohydrate epitopes to IgG Fc, creating effective therapeutic antibodies, or lysibodies. This approach is generalizable, allowing production of antibodies to poorly immunogenic carbohydrate epitopes of many Gram-positive pathogens. Lysibodies thus represent a broad class of anti-infectives.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- May 2017
- DOI:
- 10.1073/pnas.1619249114
- Bibcode:
- 2017PNAS..114.4781R