Skip to main content
SpringerLink
Log in

Vaccine Development for Epstein-Barr Virus

  • Chapter
  • First Online:
Book cover Human Herpesviruses

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1045))

Abstract

Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis and is associated with several malignancies, including nasopharyngeal carcinoma, gastric carcinoma, Hodgkin lymphoma, Burkitt lymphoma, and lymphomas in immunocompromised persons, as well as multiple sclerosis. A vaccine is currently unavailable. While monomeric EBV gp350 was shown in a phase 2 trial to reduce the incidence of infectious mononucleosis, but not the rate of EBV infection, newer formulations of gp350 including multimeric forms, viruslike particles, and nanoparticles may be more effective. A vaccine that also includes additional viral glycoproteins, lytic proteins, or latency proteins might improve the effectiveness of an EBV gp350 vaccine. Clinical trials to determine if an EBV vaccine can reduce the rate of infectious mononucleosis or posttransplant lymphoproliferative disease should be performed. The former is important since infectious mononucleosis can be associated with debilitating fatigue as well as other complications, and EBV infectious mononucleosis is associated with increased rates of Hodgkin lymphoma and multiple sclerosis. A vaccine to reduce EBV posttransplant lymphoproliferative disease would be an important proof of principle to prevent an EBV-associated malignancy. Trials of an EBV vaccine to reduce the incidence of Hodgkin lymphoma, multiple sclerosis, or Burkitt lymphoma would be difficult but feasible.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aalto SM, Juvonen E, Tarkkanen J, Volin L, Haario H, Ruutu T, Hedman K (2007) Epstein-Barr viral load and disease prediction in a large cohort of allogeneic stem cell transplant recipients. Clin Infect Dis 45:1305–1309

    Article  CAS  PubMed  Google Scholar 

  • Adhikary D, Behrends U, Moosmann A, Witter K, Bornkamm GW, Mautner J (2006) Control of Epstein-Barr virus infection in vitro by T helper cells specific for virion glycoproteins. J Exp Med 203:995–1006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adhikary D, Behrends U, Boerschmann H, Pfunder A, Burdach S, Moosmann A, Witter K, Bornkamm GW, Mautner J (2007) Immunodominance of lytic cycle antigens in Epstein-Barr virus-specific CD4+ T cell preparations for therapy. PLoS One 2:e583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alfieri C, Birkenbach M, Kieff E (1991) Early events in Epstein-Barr virus infection of human B lymphocytes. Virology 181:595–608

    Article  CAS  PubMed  Google Scholar 

  • Balfour HH Jr, Odumade OA, Schmeling DO, Mullan BD, Ed JA, Knight JA, Vezina HE, Thomas W, Hogquist KA (2013) Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students. J Infect Dis 207:80–88

    Article  CAS  PubMed  Google Scholar 

  • Brooks JM, Long HM, Tierney RJ, Shannon-Lowe C, Leese AM, Fitzpatrick M, Taylor GS, Rickinson AB (2016) Early T cell recognition of B cells following Epstein-Barr virus infection: identifying potential targets for prophylactic vaccination. PLoS Pathog 12:e1005549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bu W, Hayes GM, Liu H, Gemmell L, Schmeling DO, Radecki P, Aguilar F, Burbelo PD, Woo J, Balfour HH Jr, Cohen JI (2016) Kinetics of Epstein-Barr virus (EBV) neutralizing and virus-specific antibodies after primary infection with EBV. Clin Vaccine Immunol 23:363–369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Callan MF, Tan L, Annels N, Ogg GS, Wilson JD (1998) Direct visualization of antigen-specific CD8 T cells during the primary immune response to Epstein-Barr virus in vivo. J Exp Med 187:1395–1402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cleary ML, Epstein MA, Finerty S, Dorfman RF, Bornkamm GW, Kirkwood JK, Morgan AJ, Sklar J (1985) Individual tumors of multifocal EB virus-induced malignant lymphomas in tamarins arise from different B-cell clones. Science 228:722–724

    Article  CAS  PubMed  Google Scholar 

  • Coghill AE, Bu W, Nguyen H, Hsu WL, Yu KJ, Lou PJ, Wang CP, Chen CJ, Hildesheim A, Cohen JI (2016) High levels of antibody that neutralize B-cell infection of Epstein-Barr virus and that bind EBV gp350 are associated with a lower risk of nasopharyngeal carcinoma. Clin Cancer Res 22:3451–3457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cohen JI (2000) Epstein-Barr virus infection. N Engl J Med 343:481–492

    Article  CAS  PubMed  Google Scholar 

  • Cohen JI (2015a) Epstein-Barr virus vaccines. Clin Transl Immunol 4:e32

    Article  CAS  Google Scholar 

  • Cohen JI (2015b) Primary immunodeficiencies associated with EBV disease. Curr Top Microbiol Immunol 390(Pt 1):241–265

    PubMed  CAS  PubMed Central  Google Scholar 

  • Cohen JI, Fauci AS, Varmus H, Nabel GJ (2011) Epstein-Barr virus: an important vaccine target for cancer prevention. Sci Transl Med 3:107fs7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crotty S, Kersh EN, Cannons J, Schwartzberg PL, Ahmed R (2003) SAP is required for generating long-term humoral immunity. Nature 421:282–287

    Article  CAS  PubMed  Google Scholar 

  • Cui X, Cao Z, Sen G, Chattopadhyay G, Fuller DH, Fuller JT, Snapper DM, Snow AL, Mond JJ, Snapper CM (2013) A novel tetrameric gp350 1-470 as a potential Epstein-Barr virus vaccine. Vaccine 31:3039–3045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cui X, Cao Z, Chen Q, Arjunaraja S, Snow AL, Snapper CM (2016) Rabbits immunized with Epstein-Barr virus gH/gL or gB recombinant proteins elicit higher serum virus neutralizing activity than gp350. Vaccine 34:4050–4055

    Article  CAS  PubMed  Google Scholar 

  • Elliott SL, Suhrbier A, Miles JJ, Lawrence G, Pye SJ, Le TT, Rosenstengel A, Nguyen T, Allworth A, Burrows SR, Cox J, Pye D, Moss DJ, Bharadwaj M (2008) Phase I trial of a CD8+ T-cell peptide epitope-based vaccine for infectious mononucleosis. J Virol 82:1448–1457

    Article  CAS  PubMed  Google Scholar 

  • Emini EA, Schleif WA, Armstrong ME, Silberklang M, Schultz LD, Lehman D, Maigetter RZ, Qualtiere LF, Pearson GR, Ellis RW (1988) Antigenic analysis of the Epstein-Barr virus major membrane antigen (gp350/220) expressed in yeast and mammalian cells: implications for the development of a subunit vaccine. Virology 166:387–393

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Epstein MA, Randle BJ, Finerty S, Kirkwood JK (1986) Not all potently neutralizing, vaccine-induced antibodies to Epstein-Barr virus ensure protection of susceptible experimental animals. Clin Exp Immunol 63:485–490

    PubMed  PubMed Central  CAS  Google Scholar 

  • Finerty S, Tarlton J, Mackett M, Conway M, Arrand JR, Watkins PE, Morgan AJ (1992) Protective immunization against Epstein-Barr virus-induced disease in cottontop tamarins using the virus envelope glycoprotein gp340 produced from a bovine papillomavirus expression vector. J Gen Virol 73:449–453

    Article  CAS  PubMed  Google Scholar 

  • Gu SY, Huang TM, Ruan L, Miao YH, Lu H, Chu CM, Motz M, Wolf H (1995) First EBV vaccine trial in humans using recombinant vaccinia virus expressing the major membrane antigen. Dev Biol Stand 84:171–177

    PubMed  CAS  Google Scholar 

  • Handel AE, Williamson AJ, Disanto G, Handunnetthi L, Giovannoni G, Ramagopalan SV (2010) An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis. PLoS One. 5. pii: e12496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haque T, Johannessen I, Dombagoda D, Sengupta C, Burns DM, Bird P, Hale G, Mieli-Vergani G, Crawford DH (2006) A mouse monoclonal antibody against Epstein-Barr virus envelope glycoprotein 350 prevents infection both in vitro and in vivo. J Infect Dis 194:584–587

    Article  CAS  PubMed  Google Scholar 

  • Hartlage AS, Liu T, Patton JT, Garman SL, Zhang X, Kurt H, Lozanski G, Lustberg ME, Caligiuri MA, Baiocchi RA (2015) The Epstein-Barr virus lytic protein BZLF1 as a candidate target antigen for vaccine development. Cancer Immunol Res 3:787–794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heeke DS, Lin R, Rao E, Woo JC, McCarthy MP, Marshall JD (2016) Identification of GLA/SE as an effective adjuvant for the induction of robust humoral and cell-mediated immune responses to EBV-gp350 in mice and rabbits. Vaccine 34:2562–2569

    Article  CAS  PubMed  Google Scholar 

  • Hettich E, Janz A, Zeidler R, Pich D, Hellebrand E, Weissflog B, Moosmann A, Hammerschmidt W (2006) Genetic design of an optimized packaging cell line for gene vectors transducing human B cells. Gene Ther 13:844–856

    Article  CAS  PubMed  Google Scholar 

  • Hislop AD, Annels NE, Gudgeon NH, Leese AM, Rickinson AB (2002) Epitope-specific evolution of human CD8(+) T cell responses from primary to persistent phases of Epstein-Barr virus infection. J Exp Med 195:893–905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hjalgrim H, Askling J, Rostgaard K, Hamilton-Dutoit S, Frisch M, Zhang JS, Madsen M, Rosdahl N, Konradsen HB, Storm HH, Melbye M (2003) Characteristics of Hodgkin’s lymphoma after infectious mononucleosis. N Engl J Med 349:1324–1332

    Article  CAS  PubMed  Google Scholar 

  • Hoshino Y, Katano H, Zou P, Hohman P, Marques A, Tyring SK, Follmann D, Cohen JI (2009) Long-term administration of valacyclovir reduces the number of Epstein-Barr virus (EBV)-infected B cells but not the number of EBV DNA copies per B cell in healthy volunteers. J Virol 83:11857–11861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jackman WT, Mann KA, Hoffmann HJ, Spaete RR (1999) Expression of Epstein-Barr virus gp350 as a single chain glycoprotein for an EBV subunit vaccine. Vaccine 17:660–668

    Article  CAS  PubMed  Google Scholar 

  • Janz A, Oezel M, Kurzeder C, Mautner J, Pich D, Kost M, Hammerschmidt W, Delecluse HJ (2000) Infectious Epstein-Barr virus lacking major glycoprotein BLLF1 (gp350/220) demonstrates the existence of additional viral ligands. J Virol 74:10142–10152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jung S, Chung YK, Chang SH, Kim J, Kim HR, Jang HS, Lee JC, Chung GH, Jang YS (2001) DNA-mediated immunization of glycoprotein 350 of Epstein-Barr virus induces the effective humoral and cellular immune responses against the antigen. Mol Cells 12:41–49

    PubMed  CAS  Google Scholar 

  • Kanekiyo M, Bu W, Joyce MG, Meng G, Whittle JR, Baxa U, Yamamoto T, Narpala S, Todd JP, Rao SS, McDermott AB, Koup RA, Rossmann MG, Mascola JR, Graham BS, Cohen JI, Nabel GJ (2015) Rational design of an Epstein-Barr virus vaccine targeting the receptor-binding site. Cell 162:1090–1100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawaguchi A, Kanai K, Satoh Y, Touge C, Nagata K, Sairenji T, Inoue Y (2009) The evolution of Epstein-Barr virus inferred from the conservation and mutation of the virus glycoprotein gp350/220 gene. Virus Genes 38:215–223

    Article  CAS  PubMed  Google Scholar 

  • Khanna R, Sherritt M, Burrows SR (1999) EBV structural antigens, gp350 and gp85, as targets for ex vivo virus-specific CTL during acute infectious mononucleosis: potential use of gp350/gp85 CTL epitopes for vaccine design. J Immunol 162:3063–3069

    PubMed  CAS  Google Scholar 

  • Lees JF, Arrand JE, Pepper SD, Stewart JP, Mackett M, Arrand JR (1993) The Epstein-Barr virus candidate vaccine antigen gp340/220 is highly conserved between virus types A and B. Virology 195:578–586

    Article  CAS  PubMed  Google Scholar 

  • Leruez-Ville M, Seng R, Morand P, Boufassa F, Boue F, Deveau C, Rouzioux C, Goujard C, Seigneurin JM, Meyer L (2012) Blood Epstein-Barr virus DNA load and risk of progression to AIDS-related systemic B lymphoma. HIV Med 13:479–487

    PubMed  CAS  Google Scholar 

  • Levin LI, Munger KL, O'Reilly EJ, Falk KI, Ascherio A (2010) Primary infection with the Epstein-Barr virus and risk of multiple sclerosis. Ann Neurol 67:824–830

    PubMed  PubMed Central  Google Scholar 

  • Li Q, Turk SM, Hutt-Fletcher LM (1995) The Epstein-Barr virus (EBV) BZLF2 gene product associates with the gH and gL homologs of EBV and carries an epitope critical to infection of B cells but not of epithelial cells. J Virol 69:3987–3994

    PubMed  PubMed Central  CAS  Google Scholar 

  • Lockey TD, Zhan X, Surman S, Sample CE, Hurwitz JL (2008) Epstein-Barr virus vaccine development: a lytic and latent protein cocktail. Front Biosci 13:5916–5927

    Article  CAS  PubMed  Google Scholar 

  • Long HM, Leese AM, Chagoury OL, Connerty SR, Quarcoopome J, Quin LL, Shannon-Lowe C, Rickinson AB (2011) Cytotoxic CD4+ T cell responses to EBV contrast with CD8 responses in breadth of lytic cycle antigen choice and in lytic cycle recognition. J Immunol 187:92–101

    Article  CAS  PubMed  Google Scholar 

  • Longnecker L, Kieff E, Cohen JI (2013) Epstein-Barr virus. In: Knipe DM, Howley PM, Cohen JI, Griffith DE, Lamb RA, Martin MA, Racaniello V, Roizman B (eds) Fields virology, 6th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1898–1959

    Google Scholar 

  • Luzuriaga K, Sullivan JL (2010) Infectious mononucleosis. N Engl J Med 362:1993–2000

    Article  CAS  PubMed  Google Scholar 

  • Moghaddam A, Rosenzweig M, Lee-Parritz D, Annis B, Johnson RP, Wang F (1997) An animal model for acute and persistent Epstein-Barr virus infection. Science 276:2030–2033

    Article  CAS  PubMed  Google Scholar 

  • Morgan AJ, Epstein MA, North JR (1984) Comparative immunogenicity studies on Epstein-Barr virus membrane antigen (MA) gp340 with novel adjuvants in mice, rabbits, and cotton-top tamarins. J Med Virol 13:281–292

    Article  CAS  PubMed  Google Scholar 

  • Morgan AJ, Mackett M, Finerty S, Arrand JR, Scullion FT, Epstein MA (1988) Recombinant vaccinia virus expressing Epstein-Barr virus glycoprotein gp340 protects cottontop tamarins against EB virus-induced malignant lymphomas. J Med Virol 25:189–195

    Article  CAS  PubMed  Google Scholar 

  • Moutschen M, Léonard P, Sokal EM, Smets F, Haumont M, Mazzu P, Bollen A, Denamur F, Peeters P, Dubin G, Denis M (2007) Phase I/II studies to evaluate safety and immunogenicity of a recombinant gp350 Epstein-Barr virus vaccine in healthy adults. Vaccine 25:4697–4705

    Article  CAS  PubMed  Google Scholar 

  • Munger KL, Levin LI, O'Reilly EJ, Falk KI, Ascherio A (2011) Anti-Epstein-Barr virus antibodies as serological markers of multiple sclerosis: a prospective study among United States military personnel. Mult Scler 17:1185–1193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • North JR, Morgan AJ, Epstein MA (1980) Observations on the EB virus envelope and virus-determined membrane antigen (MA) polypeptides. Int J Cancer 26:231–240

    Article  CAS  PubMed  Google Scholar 

  • Ogembo JG, Muraswki MR, McGinnes LW, Parcharidou A, Sutiwisesak R, Tison T, Avendano J, Agnani D, Finberg RW, Morrison TG, Fingeroth JD (2015) A chimeric EBV gp350/220-based VLP replicates the virion B-cell attachment mechanism and elicits long-lasting neutralizing antibodies in mice. J Transl Med 13:50

    Article  PubMed  PubMed Central  Google Scholar 

  • Palser AL, Grayson NE, White RE, Corton C, Correia S, Ba Abdullah MM, Watson SJ, Cotten M, Arrand JR, Murray PG, Allday MJ, Rickinson AB, Young LS, Farrell PJ, Kellam P (2015) Genome diversity of Epstein-Barr virus from multiple tumor types and normal infection. J Virol 89:5222–5237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perez EM, Foley J, Tison T, Silva R, Ogembo JG (2016) Novel Epstein-Barr virus-like particles incorporating gH/gL-EBNA1 or gB-LMP2 induce high neutralizing antibody titers and EBV-specific T-cell responses in immunized mice. Oncotarget. Dec 1, online

    Google Scholar 

  • Porcu P, Eisenbeis CF, Pelletier RP, Davies EA, Baiocchi RA, Roychowdhury S, Vourganti S, Nuovo GJ, Marsh WL, Ferketich AK, Henry ML, Ferguson RM, Caligiuri MA (2002) Successful treatment of posttransplantation lymphoproliferative disorder (PTLD) following renal allografting is associated with sustained CD8(+) T-cell restoration. Blood 100:2341–2348

    Article  CAS  PubMed  Google Scholar 

  • Precopio ML, Sullivan JL, Willard C, Somasundaran M, Luzuriaga K (2003) Differential kinetics and specificity of EBV-specific CD4+ and CD8+ T cells during primary infection. J Immunol 170:2590–2598

    Article  CAS  PubMed  Google Scholar 

  • Preiksaitis JK, Cockfield SM (1998) Epstein-Barr virus and lymphoproliferative disease after transplantation. In: Bowden RA, Ljungman P, Paya CV (eds) Transplant infections. Lippincott-Raven, Philadelphia, pp 245–263

    Google Scholar 

  • Pudney VA, Leese AM, Rickinson AB, Hisop AD (2005) CD8+ immunodominance among Epstein-Barr virus lytic cycle antigens directly reflects the efficiency of antigen presentation in lytically infected cells. J Exp Med 201:349–360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qualtiere LF, Chase R, Pearson GR (1982) Purification and biologic characterization of a major Epstein Barr virus-induced membrane glycoprotein. J Immunol 129:814–818

    PubMed  CAS  Google Scholar 

  • Ragot T, Finerty S, Watkins PE, Perricaudet M, Morgan AJ (1993) Replication-defective recombinant adenovirus expressing the Epstein-Barr virus (EBV) envelope glycoprotein gp340/220 induces protective immunity against EBV-induced lymphomas in the cottontop tamarin. J Gen Virol 74:501–507

    Article  CAS  PubMed  Google Scholar 

  • Rea TD, Russo JE, Katon W, Ashley RL, Buchwald DS (2001) Prospective study of the natural history of infectious mononucleosis caused by Epstein-Barr virus. J Am Board Fam Pract 14:234–242

    PubMed  CAS  Google Scholar 

  • Rees L, Tizard EJ, Morgan AJ, Cubitt WD, Finerty S, Oyewole-Eletu TA, Owen K, Royed C, Stevens SJ, Shroff RC, Tanday MK, Wilson AD, Middeldorp JM, Amlot PL, Steven NM (2009) A phase I trial of Epstein-Barr virus gp350 vaccine for children with chronic kidney disease awaiting transplantation. Transplantation 88:1025–1029

    Article  CAS  PubMed  Google Scholar 

  • Ruiss R, Jochum S, Wanner G, Reisbach G, Hammerschmidt W, Zeidler R (2011) A virus-like particle-based Epstein-Barr virus vaccine. J Virol 85:13105–13113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santpere G, Darre F, Blanco S, Alcami A, Villoslada P, Mar Albà M, Navarro A (2014) Genome-wide analysis of wild-type Epstein-Barr virus genomes derived from healthy individuals of the 1,000 Genomes Project. Genome Biol Evol 6:846–860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarabu N, Hricik DE (2015) Introduction to solid organ transplantation. In: Ljungman P, Snydman D, Boeckh M (eds) Transplant infections. Springer, Basel, pp 19–30

    Google Scholar 

  • Sashihara J, Burbelo PD, Savoldo B, Pierson TC, Cohen JI (2009) Human antibody titers to Epstein-Barr Virus (EBV) gp350 correlate with neutralization of infectivity better than antibody titers to EBV gp42 using a rapid flow cytometry-based EBV neutralization assay. Virology 391:249–256

    Article  CAS  PubMed  Google Scholar 

  • Sashihara J, Hoshino Y, Bowman JJ, Krogmann T, Burbelo PD, Coffield VM, Kamrud K, Cohen JI (2011) Soluble rhesus lymphocryptovirus gp350 protects against infection and reduces viral loads in animals that become infected with virus after challenge. PLoS Pathog 7:e1002308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silins SL, Sherritt MA, Silleri JM, Cross SM, Elliott SL, Bharadwaj M, Le TT, Morrison LE, Khanna R, Moss DJ, Suhrbier A, Misko IS (2001) Asymptomatic primary Epstein-Barr virus infection occurs in the absence of blood T-cell repertoire perturbations despite high levels of systemic viral load. Blood 98:3739–3744

    Article  CAS  PubMed  Google Scholar 

  • Sokal EM, Hoppenbrouwers K, Vandermeulen C, Moutschen M, Léonard P, Moreels A, Haumont M, Bollen A, Smets F, Denis M (2007) Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults. J Infect Dis 196:1749–1753

    Article  PubMed  Google Scholar 

  • Steven NM, Annels NE, Kumar A, Leese AM, Kurilla MG (1997) Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus induced cytotoxic T cell response. J Exp Med 185:1605–1617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taylor GS, Long HM, Brooks JM, Rickinson AB, Hislop AD (2015) The immunology of Epstein-Barr virus-induced disease. Annu Rev Immunol 33:787–821

    Article  CAS  PubMed  Google Scholar 

  • Thacker EL, Mirzaei F, Ascherio A (2006) Infectious mononucleosis and risk for multiple sclerosis: a meta-analysis. Ann Neurol 59:499–503

    Article  PubMed  Google Scholar 

  • Thorley-Lawson DA (1979) A virus-free immunogen effective against Epstein-Barr virus. Nature 281:486–488

    Article  CAS  PubMed  Google Scholar 

  • Thorley-Lawson DA, Poodry CA (1982) Identification and isolation of the main component (gp350-gp220) of Epstein-Barr virus responsible for generating neutralizing antibodies in vivo. J Virol 43:730–736

    PubMed  PubMed Central  CAS  Google Scholar 

  • Tugizov SM, Berline JW, Palefsky JM (2003) Epstein-Barr virus infection of polarized tongue and nasopharyngeal epithelial cells. Nat Med 9:307–314

    Article  CAS  PubMed  Google Scholar 

  • van Esser JW, van der Holt B, Meijer E, Niesters HG, Trenschel R, Thijsen SF, van Loon AM, Frassoni F, Bacigalupo A, Schaefer UW, Osterhaus AD, Gratama JW, Löwenberg B, Verdonck LF, Cornelissen JJ (2001) Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell–depleted SCT. Blood 98:972–978

    Article  PubMed  Google Scholar 

  • van Esser JW, Niesters HG, van der Holt B, Meijer E, Osterhaus AD, Gratama JW, Verdonck LF, Löwenberg B, Cornelissen JJ (2002) Prevention of Epstein-Barr virus-lymphoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation. Blood 99:4364–4369

    Article  PubMed  Google Scholar 

  • Wedderburn N, Edwards JM, Desgranges C, Fontaine C, Cohen B, de Thé G (1984) Infectious mononucleosis-like response in common marmosets infected with Epstein-Barr virus. J Infect Dis 150:878–882

    Article  CAS  PubMed  Google Scholar 

  • Weiss ER, Alter G, Ogembo JG, Henderson JL, Tabak B, Bakiş Y, Somasundaran M, Garber M, Selin L, Luzuriaga K (2016) High Epstein-Barr virus load and genomic diversity are associated with generation of gp350-specific neutralizing antibodies following acute infectious mononucleosis. J Virol. 91. pii: e01562–16

    PubMed  PubMed Central  Google Scholar 

  • Woodberry T, Suscovich TJ, Henry LM, Davis JK, Frahm N, Walker BD, Scadden DT, Wang F, Brander C (2005) Differential targeting and shifts in the immunodominance of Epstein-Barr virus--specific CD8 and CD4 T cell responses during acute and persistent infection. J Infect Dis 192:1513–1524

    Article  CAS  PubMed  Google Scholar 

  • Xu J, Ahmad A, Blagdon M, D'Addario M, Jones JF, Dolcetti R, Vaccher E, Prasad U, Menezes J (1998) The Epstein-Barr virus (EBV) major envelope glycoprotein gp350/220-specific antibody reactivities in the sera of patients with different EBV-associated diseases. Int J Cancer 79:481–486

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This work was supported by the intramural research program of the National Institute of Allergy and Infectious Diseases.

Author information

Authors and Affiliations

  1. Laboratory of Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Jeffrey I. Cohen

Authors
  1. Jeffrey I. Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey I. Cohen .

Editor information

Editors and Affiliations

  1. Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan

    Yasushi Kawaguchi

  2. Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

    Yasuko Mori

  3. Department of Virology, Nagoya University Graduation School of Medicine, Nagoya, Aichi, Japan

    Hiroshi Kimura

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd. (outside the USA)

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Cohen, J.I. (2018). Vaccine Development for Epstein-Barr Virus. In: Kawaguchi, Y., Mori, Y., Kimura, H. (eds) Human Herpesviruses. Advances in Experimental Medicine and Biology, vol 1045. Springer, Singapore. https://doi.org/10.1007/978-981-10-7230-7_22

Download citation

Publish with us

Policies and ethics

Search

Navigation