title: Plant-derived recombinant F1, V, and F1-V fusion antigens of Yersinia pestis activate human cells of the innate and adaptive immune system.
abstract: Plague is still endemic in different regions of the world. Current vaccines raise concern for their side effects and limited protection, highlighting the need for an efficacious and rapidly producible vaccine. F1 and V antigens of Yersinia pestis, and F1-V fusion protein produced in Nicotiana benthamiana administered to guinea pigs resulted in immunity and protection against an aerosol challenge of virulent Y. pestis. We examined the effects of plant-derived F1, V, and F1-V on human cells of the innate immunity. F1, V, and F1-V proteins engaged TLR2 signalling and activated IL-6 and CXCL-8 production by monocytes, without affecting the expression of TNF-alpha, IL-12, IL-10, IL-1beta, and CXCL10. Native F1 antigen and recombinant plant-derived F1 (rF1) and rF1-V all induced similar specific T-cell responses, as shown by their recognition by T-cells from subjects who recovered from Y. pestis infection. Native F1 and rF1 were equally well recognized by serum antibodies of Y. pestis-primed donors, whereas serological reactivity to rF1-V hybrid was lower, and that to rV was virtually absent. In conclusion, plant-derived F1, V, and F1-V antigens are weakly reactogenic for human monocytes and elicit cell-mediated and humoral responses similar to those raised by Y. pestis infection.
authors.affiliation: Department of Internal Medicine, University of Florence and Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi, Florence, Italy. gdelprete@unifi.it
authors.forename: G
authors.initials: G
authors.lastname: Del Prete
authors.forename: L
authors.initials: L
authors.lastname: Santi
authors.forename: V
authors.initials: V
authors.lastname: Andrianaivoarimanana
authors.forename: A
authors.initials: A
authors.lastname: Amedei
authors.forename: O
authors.initials: O
authors.lastname: Domarle
authors.forename: M M
authors.initials: MM
authors.lastname: D' Elios
authors.forename: C J
authors.initials: CJ
authors.lastname: Arntzen
authors.forename: L
authors.initials: L
authors.lastname: Rahalison
authors.forename: H S
authors.initials: HS
authors.lastname: Mason
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D010931:Plague Vaccine / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014026:Nicotiana / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000502:physiology; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C508606:CXCL8 protein, human; D016207:Cytokines; D016209:Interleukin-8; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D011993:Recombinant Fusion Proteins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014614:Vaccines, Synthetic; C086725:caf1 protein, Yersinia pestis