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Tuning Subunit Vaccines with Novel TLR Triagonist Adjuvants to Generate Protective Immune Responses against Coxiella burnetii .
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2020 Feb 01; Vol. 204 (3), pp. 611-621. Date of Electronic Publication: 2019 Dec 23. - Publication Year :
- 2020
-
Abstract
- Coxiella burnetii is an obligate intracellular bacterium and the causative agent of Q fever. C. burnetii is considered a potential bioterrorism agent because of its low infectious dose; resistance to heat, drying, and common disinfectants; and lack of prophylactic therapies. Q-Vax, a formalin-inactivated whole-bacteria vaccine, is currently the only prophylactic measure that is protective against C. burnetii infections but is not U.S. Food and Drug Administration approved. To overcome the safety concerns associated with the whole-bacteria vaccine, we sought to generate and evaluate recombinant protein subunit vaccines against C. burnetii To accomplish this, we formulated C. burnetii Ags with a novel TLR triagonist adjuvant platform, which used combinatorial chemistry to link three different TLR agonists together to form one adjuvanting complex. We evaluated the immunomodulatory activity of a panel of TLR triagonist adjuvants and found that they elicited unique Ag-specific immune responses both in vitro and in vivo. We evaluated our top candidates in a live C. burnetii aerosol challenge model in C56BL/6 mice and found that several of our novel vaccine formulations conferred varying levels of protection to the challenged animals compared with sham immunized mice, although none of our candidates were as protective as the commercial vaccine across all protection criteria that were analyzed. Our findings characterize a novel adjuvant platform and offer an alternative approach to generating protective and effective vaccines against C. burnetii .<br /> (Copyright © 2020 by The American Association of Immunologists, Inc.)
- Subjects :
- Adjuvants, Immunologic
Animals
Bacterial Vaccines chemical synthesis
Combinatorial Chemistry Techniques
Disease Models, Animal
Female
Humans
Immunity
Immunogenicity, Vaccine
Mice
Mice, Inbred C57BL
Vaccines, Subunit
Bacterial Vaccines immunology
Coxiella burnetii physiology
Q Fever immunology
Toll-Like Receptors agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 204
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 31871024
- Full Text :
- https://doi.org/10.4049/jimmunol.1900991