Novel approach to the formulation of an Epstein-Barr virus antigen-based nasopharyngeal carcinoma vaccine.
Epstein-Barr virus (EBV) is associated with several malignant diseases including nasopharyngeal carcinoma (NPC), a common neoplasm throughout southeast Asia. Radiotherapy and chemotherapy can achieve remission, but a reemergence of disease is not uncommon. Therefore, there is a need for specific therapies that target the tumor through the recognition of EBV antigens. In NPC, latent membrane protein 1 (LMP1) and LMP2 offer the best opportunity for specific targeting since they are typically expressed and T-cell determinants in each of these proteins have been defined. We have attempted to maximize the opportunity of incorporating every possible CD4 and CD8 determinant in a single formulation. We have achieved this by generating a scrambled protein incorporating random overlapping peptide sets from EBNA1, LMP1, and LMP2, which was then inserted into a replication-deficient strain of adenovirus (adenovirus scrambled antigen vaccine [Ad-SAVINE]). This report describes the construction of this Ad-SAVINE construct, its utility in generating LMP1 and LMP2 responses in healthy individuals as well as NPC patients, and its capacity to define new epitopes. This formulation could have a role in NPC immunotherapy for all ethnic groups since it has the potential to activate all possible CD4 and CD8 responses within EBNA1 and LMPs.
Queensland Institute of Medical Research, Herston, QLD 4006, Australia. viviana.lutzky@qimr.edu.au
Viviana P
VP
Lutzky
Monika
M
Corban
Lea
L
Heslop
Leanne E
LE
Morrison
Pauline
P
Crooks
David F
DF
Hall
William B
WB
Coman
Scott A
SA
Thomson
Denis J
DJ
Moss
D000956:Antigens, Viral / Q000008:administration & dosage / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D002478:Cells, Cultured; D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear; D009303:Nasopharyngeal Neoplasms / Q000517:prevention & control / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic; D014763:Viral Matrix Proteins
D000956:Antigens, Viral; D019496:Cancer Vaccines; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins; C417029:EBV-encoded nuclear antigen 1