Targeting of antigen to the herpesvirus entry mediator augments primary adaptive immune responses.
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.
Lasaro
Marcio O
MO
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
Tatsis
Nia
N
Hensley
Scott E
SE
Whitbeck
J Charles
JC
Lin
Shih-Wen
SW
Rux
John J
JJ
Wherry
E John
EJ
Cohen
Gary H
GH
Eisenberg
Roselyn J
RJ
Ertl
Hildegund C
HC
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
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