Differential T cell response induced by certain recombinant oligopeptides of herpes simplex virus glycoprotein B in mice.
Much attention is presently focused on the quality of the immune response produced by helper T or regulatory cells because of its implications for vaccine development and immunomodulation. Glycoprotein B (gB) of herpes simplex virus (HSV) has been shown to induce a protective T cell response. To further characterize the nature of the T cell response, oligopeptides were expressed from the open reading frame of gB from HSV-2 (gB-2) as fusion proteins with beta-galactosidase (GZ) in E. coli. After immunopurification using an anti-GZ affinity column, oligopeptides p59 and p65, spanning amino acid residues 339-394 and 424-484 of gB-2 respectively, were examined for immunogenic response by delayed type hypersensitivity (DTH) in vivo and for antigenic response by T cell proliferation in vitro. p59 but not p65 was able to prime for both DTH and proliferative T cell response to whole HSV-2 and protect against challenge infection. However, when mice were pretreated with cyclophosphamide, p65 primed for a strong DTH response to a level similar to that induced by p59 in mice either pretreated or not treated with cyclophosphamide. This suggests that p65 contains epitopes capable of inducing both DTH and immunosuppression. Thus, when mice were primed with p65 before immunizing with HSV-2, their in vitro HSV-specific proliferative response was suppressed. Therefore, p59 is a good immunogen able to induce significant, though incomplete, protection. It could be considered for inclusion in a cocktail of subunit vaccines against HSV-2 whereas p65 or parts thereof should be excluded for this purpose.
Tizard
M L
ML
Department of Surgery, St George's Hospital Medical School, London, UK.
Chan
W L
WL
D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis / Q000276:immunology*; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D003520:Cyclophosphamide / Q000494:pharmacology; D015870:Gene Expression; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000096:biosynthesis / Q000276:immunology; D011993:Recombinant Fusion Proteins; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000276:immunology*
D000956:Antigens, Viral; D007166:Immunosuppressive Agents; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C044525:glycoprotein B, herpes simplex virus type 2; D003520:Cyclophosphamide