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Tuning Subunit Vaccines with Novel TLR Triagonist Adjuvants to Generate Protective Immune Responses against Coxiella burnetii

Authors :
Philip L. Felgner
Amanda M. Burkhardt
Medalyn Supnet
Aarti Jain
Aysegul Nalca
Eric Pearlman
Albert Zlotnik
Janine K. Tom
Samuel A Stetkevich
Sara Ruiz
D. Huw Davies
Jiin Felgner
Adrienne P Gilkes
Alexander J. Badten
Tyler J. Albin
Aaron P. Esser-Kahn
Rie Nakajima
Saikat Manna
Source :
The Journal of Immunology. 204:611-621
Publication Year :
2020
Publisher :
The American Association of Immunologists, 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.

Details

ISSN :
15506606 and 00221767
Volume :
204
Database :
OpenAIRE
Journal :
The Journal of Immunology
Accession number :
edsair.doi...........5a236f3b194b13e393b1d2488c9a2f8a