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.
Lutzky
Viviana P
VP
Queensland Institute of Medical Research, Herston, QLD 4006, Australia. viviana.lutzky@qimr.edu.au
Corban
Monika
M
Heslop
Lea
L
Morrison
Leanne E
LE
Crooks
Pauline
P
Hall
David F
DF
Coman
William B
WB
Thomson
Scott A
SA
Moss
Denis J
DJ
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