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Tuning Subunit Vaccines with Novel TLR Triagonist Adjuvants to Generate Protective Immune Responses against Coxiella burnetii.
Gilkes, Adrienne P; Albin, Tyler J; Manna, Saikat; Supnet, Medalyn; Ruiz, Sara; Tom, Janine; Badten, Alexander J; Jain, Aarti; Nakajima, Rie; Felgner, Jiin; Davies, D Huw; Stetkevich, Samuel A; Zlotnik, Albert; Pearlman, Eric; Nalca, Aysegul; Felgner, Philip L; Esser-Kahn, Aaron P; Burkhardt, Amanda M.
Afiliación
  • Gilkes AP; Vaccine Research and Design Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697.
  • Albin TJ; Institute for Immunology, University of California, Irvine, Irvine, CA 92697.
  • Manna S; Department of Chemistry, University of California, Irvine, Irvine, CA 92697.
  • Supnet M; Department of Chemistry, University of California, Irvine, Irvine, CA 92697.
  • Ruiz S; The Institute for Molecular Engineering, The University of Chicago, Chicago, IL 60637; and.
  • Tom J; Vaccine Research and Design Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697.
  • Badten AJ; Institute for Immunology, University of California, Irvine, Irvine, CA 92697.
  • Jain A; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702.
  • Nakajima R; Department of Chemistry, University of California, Irvine, Irvine, CA 92697.
  • Felgner J; Vaccine Research and Design Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697.
  • Davies DH; Institute for Immunology, University of California, Irvine, Irvine, CA 92697.
  • Stetkevich SA; Vaccine Research and Design Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697.
  • Zlotnik A; Institute for Immunology, University of California, Irvine, Irvine, CA 92697.
  • Pearlman E; Vaccine Research and Design Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697.
  • Nalca A; Institute for Immunology, University of California, Irvine, Irvine, CA 92697.
  • Felgner PL; Vaccine Research and Design Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697.
  • Esser-Kahn AP; Institute for Immunology, University of California, Irvine, Irvine, CA 92697.
  • Burkhardt AM; Vaccine Research and Design Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697.
J Immunol ; 204(3): 611-621, 2020 02 01.
Article en En | MEDLINE | ID: mdl-31871024
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.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fiebre Q / Vacunas Bacterianas / Coxiella burnetii / Receptores Toll-Like Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: J Immunol Año: 2020 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fiebre Q / Vacunas Bacterianas / Coxiella burnetii / Receptores Toll-Like Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: J Immunol Año: 2020 Tipo del documento: Article