title: Hsp110-mediated enhancement of CD4+ T cell responses to the envelope glycoprotein of members of the family Flaviviridae in vitro does not occur in vivo.
abstract: The use of heat shock proteins (HSP) to enhance activation of the immune response to chaperoned antigen is being explored for immunotherapy. Hsp110 chaperones large protein substrates more effectively than Hsp70, offering the potential to use complex antigens containing multiple epitopes in HSP-based vaccines. In this study, we investigated the ability of recombinant bovine Hsp110 to chaperone E2 glycoprotein, the major envelope protein of bovine viral diarrhea virus (BVDV) and the dominant target of neutralizing antibodies. Hsp110 formed complexes with E2, as demonstrated by immunoprecipitation. When monocytes from BVDV-immunized cattle were stimulated with these complexes and incubated with autologous CD4(+) T cells, enhanced levels of proliferation were observed. To determine the ability of these complexes to improve immunogenicity in vivo, cattle were vaccinated with either Hsp110-E2 complex or E2 only, combined with Quil-A adjuvant. In contrast to the in vitro data, cellular and humoral responses to E2 were greater in the E2-only vaccination group, indicating that complex formation had actually reduced the immunogenicity of E2. This study highlights the need for further understanding of the means by which HSP complexes are endocytosed and processed in vivo to enable the design of successful vaccine strategies.
authors.affiliation: Institute for Animal Health, Pirbright, Woking, Surrey GU24 0NF, United Kingdom.
authors.forename: Kerry
authors.initials: K
authors.lastname: McLaughlin
authors.forename: Veronica B
authors.initials: VB
authors.lastname: Carr
authors.forename: Munir
authors.initials: M
authors.lastname: Iqbal
authors.forename: Julian
authors.initials: J
authors.lastname: Seago
authors.forename: Eric A
authors.initials: EA
authors.lastname: Lefevre
authors.forename: Lucy
authors.initials: L
authors.lastname: Robinson
authors.forename: Helen
authors.initials: H
authors.lastname: Prentice
authors.forename: Bryan
authors.initials: B
authors.lastname: Charleston
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D049109:Cell Proliferation; D002478:Cells, Cultured; D001908:Diarrhea Viruses, Bovine Viral / Q000276:immunology*; D050957:HSP110 Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D047468:Immunoprecipitation; D009000:Monocytes / Q000276:immunology; D011485:Protein Binding; D062605:Quillaja Saponins; D012503:Saponins / Q000008:administration & dosage; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000378:metabolism; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D050957:HSP110 Heat-Shock Proteins; D062605:Quillaja Saponins; D012503:Saponins; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C065696:glycoprotein E, Flavivirus; C046386:Quil A