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Open AccessArticle

Effect of Different Adjuvants on the Longevity and Strength of Humoral and Cellular Immune Responses to the HCV Envelope Glycoproteins

1
National Research Council Canada, Human Health Therapeutics, 1200 Montreal Rd, Ottawa, ON K1T 0H1, Canada
2
Li Ka Shing Institute of Virology, Department of Medical Microbiology & Immunology, University of Alberta, 6-010 Katz Group-Rexall Centre for Health Research, Edmonton, AB T6G 2E1, Canada
*
Author to whom correspondence should be addressed.
Vaccines 2019, 7(4), 204; https://doi.org/10.3390/vaccines7040204
Received: 7 November 2019 / Revised: 28 November 2019 / Accepted: 30 November 2019 / Published: 3 December 2019
(This article belongs to the Section Vaccines against Infectious Diseases)
Infection by Hepatitis C virus (HCV) can lead to liver cirrhosis/hepatocellular carcinoma and remains a major cause of serious disease morbidity and mortality worldwide. However, current treatment regimens remain inaccessible to most patients, particularly in developing countries, and, therefore, the development of a novel vaccine capable of protecting subjects from chronic infection by HCV could greatly reduce the rates of HCV infection, subsequent liver pathogenesis, and in some cases death. Herein, we evaluated two different semi-synthetic archaeosome formulations as an adjuvant to the E1/E2 HCV envelope protein in a murine model and compared antigen-specific humoral (levels of anti-E1/E2 IgG and HCV pseudoparticle neutralization) and cellular responses (numbers of antigen-specific cytokine-producing T cells) to those generated with adjuvant formulations composed of mimetics of commercial adjuvants including a squalene oil-in-water emulsion, aluminum hydroxide/monophosphoryl lipid A (MPLA) and liposome/MPLA/QS-21. In addition, we measured the longevity of these responses, tracking humoral, and cellular responses up to 6 months following vaccination. Overall, we show that the strength and longevity of anti-HCV responses can be influenced by adjuvant selection. In particular, a simple admixed sulfated S-lactosylarchaeol (SLA) archaeosome formulation generated strong levels of HCV neutralizing antibodies and polyfunctional antigen-specific CD4 T cells producing multiple cytokines such as IFN-γ, TNF-α, and IL-2. While liposome/MPLA/QS-21 as adjuvant generated superior cellular responses, the SLA E1/E2 admixed formulation was superior or equivalent to the other tested formulations in all immune parameters tested. View Full-Text
Keywords: hepatitis C; glycoprotein E1/E2; archaeosome; SLA; vaccine; adjuvant; glycolipid hepatitis C; glycoprotein E1/E2; archaeosome; SLA; vaccine; adjuvant; glycolipid
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Akache, B.; Deschatelets, L.; Harrison, B.A.; Dudani, R.; Stark, F.C.; Jia, Y.; Landi, A.; Law, J.L.M.; Logan, M.; Hockman, D.; Kundu, J.; Tyrrell, D.L.; Krishnan, L.; Houghton, M.; McCluskie, M.J. Effect of Different Adjuvants on the Longevity and Strength of Humoral and Cellular Immune Responses to the HCV Envelope Glycoproteins. Vaccines 2019, 7, 204.

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