Plans for Human Trials of a Vaccine Against Epstein-Barr Virus Infection

  • M. A. Epstein


Evidence linking Epstein-Barr (EB) virus to two human cancers, endemic Burkitt’s lymphoma (BL) (Burkitt, 1963) and undifferentiated nasopharyngeal carcinoma (NPC) (Shanmugaratnam, 1971), has accumulated steadily over the years (Epstein and Morgan, 1983; Lenoir and Bornkamm, 1987; Whittle et al. 1984). Already in 1976 enough was known for it to be evident that EB virus was an essential link in a complicated chain of events leading inexorably to the malignant tumors, and it therefore seemed reasonable to suppose that if infection by the virus could be prevented, the incidence of these tumors in populations at risk would be decreased (Epstein, 1976). In view of the compelling analogy afforded by the effect of avoiding cigarette smoking on the incidence of bronchogenic carcinoma (Doll and Peto, 1976), it seemed unethical not, at least, to explore the possibility of vaccine intervention to prevent EB virus infection in the context of BL and NPC.


Fast Protein Liquid Chromatography Adjuvant Formulation Undifferentiated Nasopharyngeal Carcinoma Antiviral Vaccine Cottontop Tamarin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Allison AC, Byars NE (1986) An adjuvant formulation that selectively elicits the formation of antibodies of protective isotype and cell mediated immunity. J Immunol Methods 95:157–168.PubMedCrossRefGoogle Scholar
  2. Allison AC, Byars NE (1987) Vaccine technology: adjuvants for increased efficiency. Biotech 5:1041–1045.CrossRefGoogle Scholar
  3. Beisel C, Tanner J, Matsuo T, Thorley-Lawson D, Kezdy F, Keiff E (1985) Two major outer envelope glycoproteins of Epstein-Barr virus encoded by the same gene. J Virol 54:665–674.PubMedGoogle Scholar
  4. Biggin M, Farrell PJ, Barrell BG (1984) Transcription and DNA sequence of Gam HIL fragment of B95-8 Epstein-Barr virus. EMBO J 3:1083–1090.PubMedGoogle Scholar
  5. Burkitt D (1963) A lymphoma syndrome in tropical Africa. In Richter GW, Epstein MA (eds) International Review of Experimental Pathology. New York, London. Academic Press, Inc, pp. 67–138.Google Scholar
  6. Cammoun M, Hoerner GV, Mourali N (1974) Tumors of the nasopharynx in Tunisia: an anatomic and clinical study based on 143 cases. Cancer 33:184–192.PubMedCrossRefGoogle Scholar
  7. Churchill AE, Payne LN, Chubb RC (1969) Immunization against Marek’s disease using a live attenuated virus. Nature 221:744–747.PubMedCrossRefGoogle Scholar
  8. Clifford P (1970) A review: on the epidemiology of nasopharyngeal carcinoma. Int J Cancer 5:287–309.PubMedCrossRefGoogle Scholar
  9. Conway M, Morgan A, Mackett M (1989) Expression of Epstein-Barr virus antigen gp340/220 in mouse fibroblasts using a bovine papilloma virus vector. J Gen Virol 70:729–734.PubMedCrossRefGoogle Scholar
  10. David EM, Morgan AJ (1988) Efficient purification of Epstein-Barr virus membrane antigen gp340 by fast protein liquid chromatography. J Immunol Methods 108:231–236.PubMedCrossRefGoogle Scholar
  11. Deinhardt F, Jilg W (1986) Vaccines against hepatitis. Ann Inst Pasteur, Virol 137E:79–95.CrossRefGoogle Scholar
  12. De Schryver A, Klein G, Heweston J, Rocchi G, Henle W, Henle G, Moss DJ, Pope JH (1974) Comparison of EBV neutralization tests based on abortive infection or transformation of lymphoid cells and their relation to membrane reactive antibodies (anti MA). Int J Cancer 13:353–362.PubMedCrossRefGoogle Scholar
  13. De-Thé G (1979) Demographic studies implicating the virus in the causation of Burkitt’s lymphoma; prospects for nasopharyngeal carcinoma. In Epstein MA, Achong BG (eds), The Epstein-Barr Virus, Berlin, Heidelberg, New York: Springer, pp. 417–473.CrossRefGoogle Scholar
  14. Doll R, Peto R (1976) Mortality in relation to smoking: 20 years’ observation on male British doctors. Brit Med J 2:1525–1536.PubMedCrossRefGoogle Scholar
  15. Epstein MA (1976) Epstein-Barr virus — is it time to develop a vaccine program? J Nat Cancer Inst 56:697–700.PubMedGoogle Scholar
  16. Epstein MA (1984) A prototype vaccine to prevent Epstein-Barr (EB) virus-associated tumours. Proc Roy Soc B Lond 221:1–20.CrossRefGoogle Scholar
  17. Epstein MA, Morgan AJ (1983) Clinical consequences of Epstein-Barr virus infection and possible control by an antiviral vaccine. Clin Exp Immunol 53:257–271.PubMedGoogle Scholar
  18. Epstein MA, Morgan AJ, Finerty S, Randle BJ, Kirkwood JK (1985) Protection of cottontop tamarins against Epstein-Barr virus-induced malignant lymphoma by a prototype subunit vaccine. Nature 318:287–289.PubMedCrossRefGoogle Scholar
  19. Henle W, Henle G (1969) The relation between the Epstein-Barr virus and infectious mononucleosis, Burkitt’s lymphoma and cancer of the postnasal space. E African Med J 46:402–406.Google Scholar
  20. Hildreth JEK (1982) N-D-gluco-N-methylalanamide compounds, a new class of non-ionic detergents for membrane biochemistry. Biochem J 207:363–366.PubMedGoogle Scholar
  21. Hummel M, Thorley-Lawson DA, Kieff E (1984) An Epstein-Barr virus DNA fragment encodes messages fo the two major envelope glycoproteins (gp350/300 and gp220/200). J Virol 49:413–417.PubMedGoogle Scholar
  22. International Agency for Research on Cancer (1985) An intervention study to evaluate the effectiveness of hepatitis B vaccine for the prevention of hepatocellular carcinoma in a high risk population. IARC Working Paper 3/6:1–46.Google Scholar
  23. Kaaden OR, Dietzchold B (1974) Alterations of the immunological specificity of plasma membranes of cells infected with Marek’s disease and turkey herpes viruses. J Gen Virol 25:1–10.PubMedCrossRefGoogle Scholar
  24. Kirkwood JK, Epstein MA, Terlecki AJ (1983) Factors influencing population growth of a colony of cotton-top tamarins. Lab Animals 17:45–41.CrossRefGoogle Scholar
  25. Kirkwood JK, Epstein MA, Terlecki AJ, Underwood SJ (1985) Rearing of a second generation of cotton-top tamarins (Saguinus oedipus oediupus) in captivity. Lab Animals 19:269–272.CrossRefGoogle Scholar
  26. Lanier A, Bender T, Talbot M, Wilmeth S, Tschopp C, Henle W, Henlw G, Ritter D, Terasaki P (1980) Nasopharyngeal carcinoma in Alaskan Eskimos, Indians and Aleuts: a review of cases and study of Epstein-Barr virus, HLA and environmental risk factors. Cancer 46:2100–2106.PubMedCrossRefGoogle Scholar
  27. Lenoir GM, Bornkamm GW (1987) Burkitt’s lymphoma, a human cancer model for the study of the multistep development of cancer; proposal for a new scenario. In Klein G (ed) Advances in Viral Oncology Series Vol 7. New York, Raven Press, pp. 173–106.Google Scholar
  28. Lesnick F, Ross LJN (1975) Immunization against Marek’s disease using Marek’s disease virus-specific antigens free from infectious virus. Int J Cancer 16:153–163.CrossRefGoogle Scholar
  29. Lowe RS, Keller PM, Keech BJ, Davison AJ, Whang Y, Morgan AJ, Kieff E, Ellis RW (1987) Varicella-zoster virus as a live vector for the expression of foreign genes. Proc Natl Acad Sci USA 84:3896–3900.PubMedCrossRefGoogle Scholar
  30. Mackett M, Arrand JR (1985) Recombinant vaccinia virus induces neutralizing antibodies in rabbits against Epstein-Barr virus membrane antigen gp340. EMBO J 3229-3234.Google Scholar
  31. Marek J (1907) Multiple Nervenentzündung (polyneuritis) bei Hühern. Deutsch Tierärztl Wschr 15:412–421.Google Scholar
  32. Miller G, Shope T, Coope D, Waters C, Pagano J, Bornkamm GW, Henle W (1977) Lymphoma in cotton-top marmosets after inoculation with Epstein-Barr virus: tumor incidence, histologic spectrum, antibody responses, demonstration of viral DNA, and characterization of viruses. J Exp Med 145:948–967.PubMedCrossRefGoogle Scholar
  33. Morein B, Sundquist B, Höglund S, Dalsgaard K, Osterhaus A (1984) Iscom, a novel structure for antigenic presentation of membrane proteins from enveloped viruses. Nature 308:457–460.PubMedCrossRefGoogle Scholar
  34. Morein B, Lövgren K, Höglund S, Sundquist B (1987) The iscom: an immunostimulating complex. Immunol Today 8:333–338.CrossRefGoogle Scholar
  35. Morgan AJ, North JR, Epstein MA (1983) Purification and properties of the gp340 component of Epstein-Barr (EB) virus membrane antigen (MA) in an immunogenic form. J Med Virol 25:189–195.CrossRefGoogle Scholar
  36. Morgan AJ, Smith AR, Barker RN, Epstein MA (1984) A structural investigation of the Epstein-Barr (EB) virus membrane antigen glycoprotein, gp340. J Gen Virol 65:397–404.PubMedCrossRefGoogle Scholar
  37. Morgan AJ, Finerty S, Lovgren K, Scullion FT, Morein B (1988a) Prevention of Epstein-Barr (EB) virus-induced lymphoma in cottontop tamarins by vaccination with the EB virus envelope glycoprotein gp340 incorporated into immune-stimulating complexes. J Gen Virol 69:2093–2096.PubMedCrossRefGoogle Scholar
  38. Morgan AJ, Mackett M, Finerty S, Arrand J, Scullion F, Epstein MA (1988b) Recombinant vaccinia virus expressing Epstein-Barr virus glycoprotein gp340 protects cottontop tamarins against EB virus-incuded lymphomas. J Med Virol 25:189–195.PubMedCrossRefGoogle Scholar
  39. Morgan AJ, Allison AC, Finerty S, Scullion FT, Byars NE, Epstein MA (1989) Validation of a first generation Epstein-Barr virus vaccine preparation suitable for human use. J Med Virol (in press).Google Scholar
  40. Moss DJ, Pope JH (1972) Assay of the infectivity of Epstein-Barr virus by transformation of human leucocytes in vitro. J Gen Virol 17:233–236.PubMedCrossRefGoogle Scholar
  41. North JR, Morgan AJ, Thompson JL, Epstein MA (1982) Quantification of an EB virus-associated membrane antigen (MA) component. J Virol Methods 5:55–65.PubMedCrossRefGoogle Scholar
  42. Okazaki W, Purchase HG, Burmester BR (1970) Protection against Marek’s disease by vaccination with a herpesvirus of turkeys. Avian Dis 14:413–429.PubMedCrossRefGoogle Scholar
  43. Payne LN, Frazier JA, Powell PC (1976) Pathogenesis of Marek’s disease. In Richter GW, Epstein MA (eds) Internat Rev Exp Path, Vol. 16, New York, San Francisco, London; Academic Press, pp. 59–154.Google Scholar
  44. Provost PJ, Keller PM, Banker FS, Keech BJ, Klein HJ, Lowe RS, Morton DH, Phelps AH, McAleer WJ, Ellis RW (1987) Successful infection of the common marmoset (Callithrix jacchus) with human varicella-zoster virus. J Virol 61:2951–2955.PubMedGoogle Scholar
  45. Purtilo DT, Sakamoto K, Barnabei V, Seeley J, Beechtold T, Rogers G, Yetz J, Harada S (1986) Epstein-Barr virus-induced diseases in boys with the X-linked lymphoproliferative syndrome (XLP). Am J Med 73:49–56.CrossRefGoogle Scholar
  46. Randle BJ, Epstein MA (1984) A highly sensitive enzyme-linked immunosorbent assay to quantitate antibodies to Epstein-Barr virus membrane antigen gp340. J Virol Methods 9:201–208.PubMedCrossRefGoogle Scholar
  47. Schultz LD, Tanner J, Hofmann K, Emini E, Kieff E, Ellis RW (1987) Expression and analysis of EBV gp350 in yeast Saccharomyces cerevisiae. In Levine PH, Ablashi DV, Nonoyama M, Pearson GR, Glaser R (eds), Epstein-Barr Virus and Human Disease. Clifton, New Jersey, Humana Press, pp. 475–478.CrossRefGoogle Scholar
  48. Shanmugaratnam K (1971) Studies on the etiology of nasopharyngeal carcinoma. In Richter GW, Epstein MA (eds) Int Rev Exp Path, New York, London, Academic Press Inc, 10: pp. 361–413.Google Scholar
  49. Speijers G, Danse L, Bewary E, Strik J, Vos J (1988) Local reactions of the saponin Quil A and a Quil A-containing iscom measles vaccine after intramuscular injection of rats: a comparison with the effects of DPT-polio vaccine. Fundamental and Appl Toxicol 10:425–430.CrossRefGoogle Scholar
  50. Takahaski M, Otsuka T, Okuno Y, Asano Y, Yazaki T, Isomura S (1974) Live varicella vaccine used to prevent the spread of varicella in children in hospital. Lancet 2:1288–1290.CrossRefGoogle Scholar
  51. Whang Y, Silberklang M, Morgan A, Munshi S, Lenny AB, Ellis RW, Kieff E (1987) Expression of Epstein-Barr virus gp350-220 gene in rodent and primate cells. J Virol 61:1796–1807.PubMedGoogle Scholar
  52. Whittle HC, Brown J, Marsh K, Greenwood BM, Seidelin P, Tighe H, Wedderburn L (1984) T cell control of B cells infected with EB virus is lost during P. falciparum malaria. Nature 312:229–250.CrossRefGoogle Scholar
  53. Zuckerman AJ (1985) Prevention of hepatocellular carcinoma by immunization against hepatitis B. In Epstein MA, Richter GW (eds) Int Rev Exp Path. Orlando, San Diego, New York, London, Toronto, Montreal, Sydney, Tokyo, Academic Press Inc, 25: pp. 59–81.Google Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • M. A. Epstein
    • 1
  1. 1.Nuffield Department of Clinical MedicineUniversity of Oxford John Radcliffe HospitalOxfordUK

Personalised recommendations