title: Protective immunization against Epstein-Barr virus-induced disease in cottontop tamarins using the virus envelope glycoprotein gp340 produced from a bovine papillomavirus expression vector.
abstract: Inoculation with Epstein-Barr virus (EBV) induces malignant lymphomas in the cottontop tamarin (Saguinus oedipus oedipus). This provides an experimental animal model for assessing the efficacy of candidate EBV vaccines which are intended to reduce the incidence of human tumours associated with EBV infection. Previous work has shown that experimental vaccines based on the major virus envelope glycoprotein gp340 prepared from the membranes of EBV-infected cells are effective in protecting cottontop tamarins against EBV-induced disease. However, not all purified gp340 preparations induce protective immunity against EBV lymphoma in the tamarin. In this work, cottontop tamarins were immunized with recombinant gp340, produced using a bovine papillomavirus (BPV) expression vector, and a threonyl muramyl dipeptide adjuvant formulation. Although the recombinant-derived gp340 lacked the membrane anchor sequence of authentic gp340 and was expressed in mouse cells, it was immunogenic and induced virus-neutralizing antibodies. Healthy vaccinated tamarins were protected against EBV-induced disease. The demonstration that a recombinant gp340 product is able to elicit protective immunity in the cottontop tamarin is a significant step in the development of an EBV vaccine because previously it had not been clear whether a recombinant product would have the exact tertiary structure, including the necessary carbohydrate components, to induce protective immunity. A recombinant gp340 vaccine offers various advantages over production of the authentic molecule by laborious biochemical separation, including lower cost and the absence of potentially oncogenic EBV DNA. Therefore, recombinant gp340 produced using the BPV expression vector is suitable for development as a candidate EBV vaccine for a human Phase I trial and beyond.
authors.affiliation: Department of Pathology, School of Medical Sciences, University of Bristol, U.K.
authors.forename: S
authors.initials: S
authors.lastname: Finerty
authors.forename: J
authors.initials: J
authors.lastname: Tarlton
authors.forename: M
authors.initials: M
authors.lastname: Mackett
authors.forename: M
authors.initials: M
authors.lastname: Conway
authors.forename: J R
authors.initials: JR
authors.lastname: Arrand
authors.forename: P E
authors.initials: PE
authors.lastname: Watkins
authors.forename: A J
authors.initials: AJ
authors.lastname: Morgan
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine; D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D002051:Burkitt Lymphoma / Q000517:prevention & control*; D004195:Disease Models, Animal; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D004854:Herpesvirus 4, Human / Q000276:immunology*; D007114:Immunization; D027383:Papillomaviridae / Q000235:genetics; D012452:Saguinus; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014763:Viral Matrix Proteins; D014765:Viral Vaccines
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D014765:Viral Vaccines; D000119:Acetylmuramyl-Alanyl-Isoglutamine