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Vaccine. 2018 Nov 14. pii: S0264-410X(18)31496-8. doi: 10.1016/j.vaccine.2018.10.099. [Epub ahead of print]
Characterization of the innate stimulatory capacity of plant-derived virus-like particles bearing influenza hemagglutinin.
Won SY1, Hunt K1, Guak H1, Hasaj B1, Charland N2, Landry N2, Ward BJ3, Krawczyk CM4.
Author information
Abstract
Cell-mediated immunity is an important component of immediate and long-term anti-viral protection. Dendritic cells (DCs) are essential for the induction of cell-mediated immunity by instructing the activation and differentiation of antigen-specific T cell responses. Activated DCs that express co-stimulatory molecules and pro-inflammatory cytokines are necessary to promote the development of type 1 immune responses required for viral control. Here we report that plant-derived virus-like particles (VLPs) bearing influenza hemagglutinins (HA) directly stimulate mouse and human DCs. DCs exposed to H1- and, to a lesser extent, H5-VLPs in vitro rapidly express co-stimulatory molecules and produce pro-inflammatory cytokines including IL-12, IL-6 and TNFα. Furthermore, these VLPs support the activation and differentiation of antigen-specific T cell responses. Mechanistically, H1-VLPs stimulate the activation of kinases typically activated downstream of pattern recognition receptors including AKT, p38, and p42/44 ERK. In vivo, immunization with plant-derived VLPs induce the accumulation of both cDC1s and cDC2 in the draining lymph node and a corresponding increase in T and B cells. VLPs devoid of HA protein activate DCs, suggesting they are intrinsically immunostimulatory. Together, the results demonstrate that these candidate plant-derived VLP vaccines have an inherent and direct stimulatory effect on DCs and can enhance the ability of DCs to promote Type 1 immune responses.
KEYWORDS:
Dendritic cell; Influenza; Innate immunity; Plant-derived vaccine; Type 1 response; Virus-like particle
PMID: 30448064 DOI: 10.1016/j.vaccine.2018.10.099
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Characterization of the innate stimulatory capacity of plant-derived virus-like particles bearing influenza hemagglutinin.
Won SY1, Hunt K1, Guak H1, Hasaj B1, Charland N2, Landry N2, Ward BJ3, Krawczyk CM4.
Author information
Abstract
Cell-mediated immunity is an important component of immediate and long-term anti-viral protection. Dendritic cells (DCs) are essential for the induction of cell-mediated immunity by instructing the activation and differentiation of antigen-specific T cell responses. Activated DCs that express co-stimulatory molecules and pro-inflammatory cytokines are necessary to promote the development of type 1 immune responses required for viral control. Here we report that plant-derived virus-like particles (VLPs) bearing influenza hemagglutinins (HA) directly stimulate mouse and human DCs. DCs exposed to H1- and, to a lesser extent, H5-VLPs in vitro rapidly express co-stimulatory molecules and produce pro-inflammatory cytokines including IL-12, IL-6 and TNFα. Furthermore, these VLPs support the activation and differentiation of antigen-specific T cell responses. Mechanistically, H1-VLPs stimulate the activation of kinases typically activated downstream of pattern recognition receptors including AKT, p38, and p42/44 ERK. In vivo, immunization with plant-derived VLPs induce the accumulation of both cDC1s and cDC2 in the draining lymph node and a corresponding increase in T and B cells. VLPs devoid of HA protein activate DCs, suggesting they are intrinsically immunostimulatory. Together, the results demonstrate that these candidate plant-derived VLP vaccines have an inherent and direct stimulatory effect on DCs and can enhance the ability of DCs to promote Type 1 immune responses.
KEYWORDS:
Dendritic cell; Influenza; Innate immunity; Plant-derived vaccine; Type 1 response; Virus-like particle
PMID: 30448064 DOI: 10.1016/j.vaccine.2018.10.099
Free full text