title: Targeting of antigen to the herpesvirus entry mediator augments primary adaptive immune responses.
abstract: Interactions between the herpesvirus entry mediator (HVEM) and the B- and T-lymphocyte attenuator (BTLA) inhibit B and T cell activation. HVEM-BTLA interactions are blocked by herpes simplex virus (HSV) glycoprotein D (gD) through binding of its N-terminal domain to the BTLA binding site of HVEM. In this study, we inserted viral antigens into the C-terminal domain of gD and expressed these antigens with plasmid or E1-deleted (replication-defective) adenovirus vectors. Viral antigens fused to gD induced T and B cell responses to the antigen that were far more potent than those elicited by the same antigen expressed without gD. The immunopotentiating effect required binding of the gD chimeric protein to HVEM. Overall, the studies demonstrate that targeting of antigen to the BTLA binding site of HVEM augments the immunogenicity of vaccines.
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Marcio O
authors.initials: MO
authors.lastname: Lasaro
authors.forename: Nia
authors.initials: N
authors.lastname: Tatsis
authors.forename: Scott E
authors.initials: SE
authors.lastname: Hensley
authors.forename: J Charles
authors.initials: JC
authors.lastname: Whitbeck
authors.forename: Shih-Wen
authors.initials: SW
authors.lastname: Lin
authors.forename: John J
authors.initials: JJ
authors.lastname: Rux
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.forename: Gary H
authors.initials: GH
authors.lastname: Cohen
authors.forename: Roselyn J
authors.initials: RJ
authors.lastname: Eisenberg
authors.forename: Hildegund C
authors.initials: HC
authors.lastname: Ertl
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015683:Gene Products, gag / Q000276:immunology; D005822:Genetic Vectors; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D010641:Phenotype; D011485:Protein Binding; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D015683:Gene Products, gag; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1