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      Improving the Th1 cellular efficacy of the lead Yersinia pestis rF1-V subunit vaccine using SA-4-1BBL as a novel adjuvant.

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          Abstract

          The lead candidate plague subunit vaccine is the recombinant fusion protein rF1-V adjuvanted with alum. While alum generates Th2 regulated robust humoral responses, immune protection against Yersinia pestis has been shown to also involve Th1 driven cellular responses. Therefore, the rF1-V-based subunit vaccine may benefit from an adjuvant system that generates a mixed Th1 and humoral immune response. We herein assessed the efficacy of a novel SA-4-1BBL costimulatory molecule as a Th1 adjuvant to improve cellular responses generated by the rF1-V vaccine. SA-4-1BBL as a single adjuvant had better efficacy than alum in generating CD4(+) and CD8(+) T cells producing TNFα and IFNγ, signature cytokines for Th1 responses. The combination of SA-4-1BBL with alum further increased this Th1 response as compared with the individual adjuvants. Analysis of the humoral response revealed that SA-4-1BBL as a single adjuvant did not generate a significant Ab response against rF1-V, and SA-4-1BBL in combination with alum did not improve Ab titers. However, the combined adjuvants significantly increased the ratio of Th1 regulated IgG2c in C57BL/6 mice to the Th2 regulated IgG1. Finally, a single vaccination with rF1-V adjuvanted with SA-4-1BBL+alum had better protective efficacy than vaccines containing individual adjuvants. Taken together, these results demonstrate that SA-4-1BBL improves the protective efficacy of the alum adjuvanted lead rF1-V subunit vaccine by generating a more balanced Th1 cellular and humoral immune response. As such, this adjuvant platform may prove efficacious not only for the rF1-V vaccine but also against other infections that require both cellular and humoral immune responses for protection.

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          Author and article information

          Journal
          Vaccine
          Vaccine
          1873-2518
          0264-410X
          Sep 3 2014
          : 32
          : 39
          Affiliations
          [1 ] Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202, United States; Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202, United States.
          [2 ] Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202, United States; Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40202, United States.
          [3 ] Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202, United States; Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40202, United States. Electronic address: matt.lawrenz@louisville.edu.
          [4 ] Institute for Cellular Therapeutics, University of Louisville, Louisville, KY 40202, United States; Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202, United States. Electronic address: haval.shirwan@louisville.edu.
          Article
          S0264-410X(14)00941-4
          10.1016/j.vaccine.2014.07.015
          25045812
          2eec1fb6-b81a-448c-acf8-717b49bb1108
          Copyright © 2014 Elsevier Ltd. All rights reserved.
          History

          4-1BB,4-1BBL,Adjuvant,Alum,CD137,Costimulation,Plague,SA-4-1BBL,Subunit vaccine,Th(1) response,rF1-V

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