title: Evaluation of a non-viral vaccine in smallpox-vaccinated individuals and immunized HLA-transgenic mice.
abstract: The current poxvirus vaccine is associated with rare, but serious adverse events. Therefore, we investigated a non-replicating approach to vaccine design. Peptides encoding potential HLA-binding motifs were derived from the orthopoxvirus genes, D8L, A27L, and C12L (the IL-18-binding protein [vIL18BP105]), all of which are preserved among poxviruses that infect humans, and which may be a target of host immunity. The peptides were tested with poxvirus-vaccinated human PBMC and serum for eliciting memory responses, as well as with splenocytes and serum from peptide-immunized, human HLA-DR04 transgenic (HLA tg) mice. vIL18BP105 induced 5-fold proliferation of vaccinated-donor PBMC over non-vaccinated (P<0.001), including IL-2-producing CD8+ cells. Serum IgG recognizing vIL18BP105 was detected (P<0.002 vs non-vaccinated) by ELISA. Viral peptides were conjugated to the HLA-targeting mAb, L243, for immunization of HLA tg mice. Splenocytes from vIL18BP105-L243-immunized mice proliferated upon exposure to vIL18BP105 (P<0.001). Proliferating splenocytes were interferon-γ-producing CD4(+)CD45RA(neg). vIL18BP105-L243-immunized mice generated IgG more rapidly than free-peptide-immunized mice. Peptide-specific antibody was also detected when different L243-peptide conjugates were combined. vIL18BP, by eliciting human memory responses, is a viable antigen for inclusion in a virus-free vaccine. The immunogenicity of peptides was boosted by conjugation to L243, whether administered alone or combined.
authors.affiliation: Center for Molecular Medicine and Immunology/Garden State Cancer Center (CMMI/GSCC), 300 The American Road, Morris Plains, NJ 07950, USA. ataylor@gscancer.org
authors.forename: Alice P
authors.initials: AP
authors.lastname: Taylor
authors.forename: Boby
authors.initials: B
authors.lastname: Makabi-Panzu
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Chen
authors.forename: David V
authors.initials: DV
authors.lastname: Gold
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D001665:Binding Sites; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation; D005814:Genes, Viral / Q000276:immunology*; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020382:Interleukin-18 / Q000737:chemistry / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018155:Orthopoxvirus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D012899:Smallpox / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D018796:Immunoconjugates; D020382:Interleukin-18; D007376:Interleukin-2; D010455:Peptides; D014765:Viral Vaccines; D007371:Interferon-gamma