Intranasal c-di-GMP-adjuvanted plant-derived H5 influenza vaccine induces multifunctional Th1 CD4+ cells and strong mucosal and systemic antibody responses in mice |
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Authors: | Madhun Abdullah S Haaheim Lars R Nøstbakken Jane Kristin Ebensen Thomas Chichester Jessica Yusibov Vidadi Guzman Carlos A Cox Rebecca J |
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Institution: | a Influenza Centre, The Gade Institute, University of Bergen, N-5021 Bergen, Norway b Myrdalskogen 95, N-5117 Ulset, Norway c Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany d Fraunhofer USA Center for Molecular Biotechnology, Newark, DE 19711, USA |
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Abstract: | Vaccination is the best available measure of limiting the impact of the next influenza pandemic. Ideally, a candidate pandemic influenza vaccine should be easy to administer and should elicit strong mucosal and systemic immune responses. Production of influenza subunit antigen in transient plant expression systems is an alternative to overcome the bottleneck in vaccine supply during influenza pandemic. Furthermore, a needle-free intranasal influenza vaccine is an attractive approach, which may provide immunity at the portal of virus entry.The present study investigated the detailed humoral and cellular immune responses in mice vaccinated intranasally or intramuscularly with plant-derived influenza H5N1 (A/Anhui/1/05) antigen alone or formulated with bis-(3′,5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) as adjuvant. The use of c-di-GMP as intramuscular adjuvant did not enhance the immune response to plant-derived influenza H5 antigen. However, intranasal c-di-GMP-adjuvanted vaccine induced strong mucosal and systemic humoral immune responses. Additionally, the intranasal vaccine elicited a balanced Th1/Th2 profile and, most importantly, high frequencies of multifunctional Th1 CD4+ cells. Our results highlight that c-di-GMP is a promising mucosal adjuvant for pandemic influenza vaccine development. |
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Keywords: | Influenza H5N1 Multifunctional Th1 Plant-derived antigen c-di-GMP |
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