Superior immunogenicity of HCV envelope glycoproteins when adjuvanted with cyclic-di-AMP,a STING activator or archaeosomes |
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| Institution: | 1. Saarland University, Biopharmaceutics and Pharmaceutical Technology, Saarbruecken, Germany;2. Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Saarbruecken, Germany;3. Helmholtz Center for Infection Research Braunschweig, Department of Vaccinology and Applied Microbiology, Braunschweig, Germany;1. Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;2. Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina, Chapel Hill, NC 27599, USA;3. Curriculum of Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA;4. Oral Biology Curriculum, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;5. Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA;6. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;7. Institute for Inflammatory Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;8. Center for Translational Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA |
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| Abstract: | Three decades after the discovery, hepatitis C virus (HCV) is still the leading cause of liver transplantation and poses a major threat to global health. In spite of recent advances in the development of direct acting antivirals, there is still a need for a prophylactic vaccine to limit the virus spread and protect at-risk populations, especially in developing countries, where the cost of the new treatments may severely limit access. The use of recombinant HCV glycoproteins E1E2 (rE1E2) in combination with the MF59, an oil-in-water emulsion-based adjuvant, has previously been shown to reduce the rate of chronicity in chimpanzees and to induce production of cross-neutralizing antibodies and cellular immune responses in human volunteers. To further improve neutralizing antibody responses in recipients along with robust T cell responses, we have explored the immunogenicity of different adjuvants when formulated with the HCV rE1E2 vaccine in mice.Our data show that cyclic di-adenosine monophosphate (c-di-AMP) and archaeosomes elicit strong neutralizing antibodies similar to those elicited using aluminum hydroxide/monophosphoryl lipid A (Alum/monophos. /MPLA) and MF59. However, both c-di-AMP and archaeosomes induced a more robust cellular immune response, which was confirmed by the detection of vaccine-specific poly-functional CD4+ T cells. We conclude that these adjuvants may substantially boost the immunogenicity of our E1E2 vaccine. In addition, our data also indicates that use of a partial or exclusive intranasal immunization regimen may also be feasible using c-di-AMP as adjuvant. |
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| Keywords: | Vaccine Adjuvant HCV rE1E2 glycoproteins c-di-AMP Archaeosomes |
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