Eliminating Factor H-Binding Activity of Borrelia burgdorferi CspZ Combined with Virus-Like Particle Conjugation Enhances Its Efficacy as a Lyme Disease Vaccine
| Autor: | Kaspars Tars, Ilva Lieknina, Svetlana Kotelovica, Yi-Pin Lin, Ashley L. Marcinkiewicz, Xiuli Yang, Utpal Pal, Peter Kraiczy |
|---|---|
| Přispěvatelé: | Bagnoli, Fabio |
| Rok vydání: | 2018 |
| Předmět: |
Male
lcsh:Immunologic diseases. Allergy 0301 basic medicine 030106 microbiology Immunology Serum Bactericidal Antibody Assay virus-like particles Epitope Microbiology Mice 03 medical and health sciences Antigen vaccine Borrelia Animals Lyme disease Immunology and Allergy Vaccines Virus-Like Particle ddc:610 Borrelia burgdorferi Original Research Innate immune system biology Immunogenicity Immunization Passive Lyme Disease Vaccines factor H biology.organism_classification Antibodies Bacterial 3. Good health Complement system CspZ 030104 developmental biology Complement Factor H biology.protein Antibody lcsh:RC581-607 Bacterial Outer Membrane Proteins |
| Zdroj: | Frontiers in Immunology, Vol 9 (2018) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2018.00181 |
| Popis: | The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the most common tick-borne disease in the U.S and Europe. No potent human vaccine is currently available. The innate immune complement system is vital to host defense against pathogens, as complement activation on the surface of spirochetes results in bacterial killing. Complement system is inhibited by the complement regulator factor H. To escape killing, B. burgdorferi produces an outer surface protein CspZ that binds factor H to inhibit complement activation on the cell surface. Immunization with CspZ alone does not protect mice from infection, which we speculate is because factor H-binding cloaks potentially protective epitopes. We modified CspZ by conjugating to virus-like particles (VLP-CspZ) and eliminating factor H binding (modified VLP-CspZ) to increase immunogenicity. We observed greater bactericidal antibody titers in mice vaccinated with modified VLP-CspZ: A serum dilution of 1:395 (modified VLP-CspZ) vs 1:143 (VLP-CspZ) yielded 50% borreliacidal activity. Immunizing mice with modified VLP-CspZ cleared spirochete infection, as did passive transfer of elicited antibodies. This work developed a novel Lyme disease vaccine candidate by conjugating CspZ to VLP and eliminating factor H-binding ability. Such a strategy of conjugating an antigen to a VLP and eliminating binding to the target ligand can serve as a general model for developing vaccines against other bacterial infectious agents. |
| Databáze: | OpenAIRE |
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