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Vaccination

Efficacy of donor vaccination before hematopoietic cell transplantation and recipient vaccination both before and early after transplantation

Bone Marrow Transplantation volume 33, pages 337–346 (2004)Cite this article

Summary:

Allogeneic hematopoietic cell transplantation is followed by humoral immunodeficiency. We evaluated whether antibody levels can be improved by recipient vaccination on day −1 and 50 and whether the levels can be further improved by donor vaccination on day −20. A total of 85 patients were randomized or assigned to one of the following strategies of immunization with Streptococcus pneumoniae polysaccharides, Haemophilus influenzae polysaccharide–protein conjugate, tetanus toxoid (protein recall antigen) and hepatitis B surface antigen (protein neo-antigen): (1) donor on day −20, recipient on days −1, +50 and +365 (D−20R−1,50,365); (2) donor nil, recipient on days −1, +50 and +365 (DNR−1,50,365); or (3) donor nil, recipient on day +365 (DNR365). For H. influenzae and tetanus, IgG levels after grafting were the highest in the D−20R−1,50,365 patients, intermediate in the DNR−1,50,365 patients and the lowest in the DNR365 patients. For S. pneumoniae and hepatitis B, antibody levels appeared to be similar in all three patient groups. The results suggest that for polysaccharide–protein conjugate antigens or protein recall antigens, recipient immunization on days −1 and 50 improves antibody levels and that donor vaccination on day −20 further improves the levels. In contrast, neither recipient immunization on days −1 and 50 nor donor immunization on day −20 appears to be efficacious for polysaccharide antigens and poorly immunogenic protein neo-antigens.

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References

  1. Parkman R, Weinberg KI . Immunological reconstitution following hematopoietic stem cell transplantation. In: Thomas ED, Blume KG, Forman SJ (eds). Hematopoietic Cell Transplantation. Blackwell Science: Malden, 1999, 704–711.

    Google Scholar 

  2. Storek J, Witherspoon RP . Immunologic reconstitution after hematopoietic stem cell transplantation. In: Atkinson K (ed). Clinical Bone Marrow and Blood Stem Cell Transplantation. Cambridge University Press: Cambridge, in press.

  3. Sheridan JF . Immunoglobulin G subclass deficiency and pneumococcal infection after allogeneic BMT. Blood 1990; 75: 1583–1586.

    CAS  Google Scholar 

  4. Aucouturier P, Barra A, Intrator L et al. Long lasting IgG subclass and antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation. Blood 1987; 70: 779–785.

    CAS  Google Scholar 

  5. Riches PG, Walker SA, Rogers TR et al. Relative deficiency of serum IgA, IgG2 and IgG4 during reconstitution following BMT: relationship to infection. Bone Marrow Transplant 1986; 1 (Suppl 1): 53.

    Google Scholar 

  6. Sullivan KM, Storek J, Kopecky KJ et al. A controlled trial of long-term administration of intravenous immunoglobulin to prevent late infection and chronic GVHD following marrow transplantation: Clinical outcome and effect on subsequent immune recovery. Biol Blood Marrow Transplant 1996; 2: 44–53.

    CAS  Google Scholar 

  7. Molrine DC, Antin JH, Guinan EC et al. Donor immunization with pneumococcal conjugate vaccine and early protective antibody responses following allogeneic hematopoietic cell transplantation. Blood 2003; 101: 831–836.

    Article  CAS  Google Scholar 

  8. Molrine DC, Guinan EC, Antin JH et al. Donor immunization with Haemophilus influenzae type B (Hib)-conjugate vaccine in allogeneic bone marrow transplantation. Blood 1996; 87: 3012–3018.

    CAS  Google Scholar 

  9. Dykewicz CA, Jaffe HW, Kaplan JE . Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant 2000; 6: 659–713, 715; 717–627; quiz 729–633.

    Google Scholar 

  10. Wimperis JZ, Gottlieb D, Duncombe AS et al. Requirements for the adoptive transfer of antibody responses to a priming antigen in man. J Immunol 1990; 144: 541–547.

    CAS  PubMed  Google Scholar 

  11. Witherspoon RP, Storb R, Ochs HD et al. Recovery of antibody production in human allogeneic marrow graft recipients: influence of time posttransplantation, the presence or absence of chronic graft-versus-host disease, and antithymocyte globulin treatment. Blood 1981; 58: 360–368.

    CAS  Google Scholar 

  12. Guinan EC, Molrine DC, Antin JH et al. Polysaccharide conjugate vaccine responses in bone marrow transplant patients. Transplantation 1994; 57: 677–684.

    Article  CAS  Google Scholar 

  13. Amlot PL, Hayes AE, Gray D et al. Human immune responses in vivo to protein (KLH) and polysaccharide (DNP-Ficoll) neoantigens: normal subjects compared with bone marrow transplant patients on cyclosporine. Clin Exp Immunol 1986; 64: 125–135.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Barra A, Cordonnier C, Preziosi MP et al. Immunogenicity of Haemophilus influenzae type b conjugate vaccine in allogeneic bone marrow recipients. J Infect Dis 1992; 166: 1021–1028.

    Article  CAS  Google Scholar 

  15. Parkkali T, Ruutu T, Stenvik M et al. Loss of protective immunity to polio, diphteria and Haemophilus influenzae type b after allogeneic bone marrow transplantation. APMIS 1996; 104: 383–388.

    Article  CAS  Google Scholar 

  16. Donnenberg AD, Hess AD, Duff SC et al. Regeneration of genetically restricted immune functions after human bone marrow transplantation: influence of four different strategies for GVHD prophylaxis. Transplant Proc 1987; 19 (Suppl 7): 144–152.

    CAS  PubMed  Google Scholar 

  17. Saxon A, Mitsuyasu R, Stevens R et al. Designed transfer of specific immune responses with bone marrow transplantation. J Clin Invest 1986; 78: 959–967.

    Article  CAS  Google Scholar 

  18. Gottlieb DJ, Cryz Jr SJ, Furer E et al. Immunity against Pseudomonas aeruginosa adoptively transferred to bone marrow transplant recipients. Blood 1990; 76: 2470–2475.

    CAS  PubMed  Google Scholar 

  19. Labadie J, VanTol JD, Dijkstra NH et al. Transfer of specific immunity from donor to recipient of an allogeneic bone marrow graft: effect of conditioning on the specific immune response of the graft recipient. Br J Haematol 1992; 80: 381–390.

    Article  CAS  Google Scholar 

  20. Ljungman P, Wiklund-Hammarsten M, Duraj V et al. Response to tetanus toxoid immunization after allogeneic bone marrow transplantation. J Infect Dis 1990; 162: 496–500.

    Article  CAS  Google Scholar 

  21. Ljungman P, Lewensohn-Fuchs I, Hammarstrom V et al. Long-term immunity to measles, mumps and rubella after allogeneic bone marrow transplantation. Blood 1994; 84: 657–663.

    CAS  PubMed  Google Scholar 

  22. Bensinger WI, Martin P, Storer B et al. Transplantation of bone marrow as compared with peripheral blood cells from HLA-identical relatives in patients with hematologic malignancies. N Engl J Med 2001; 344: 175–181.

    Article  CAS  Google Scholar 

  23. Storek J, Dawson MA, Storer B et al. Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood 2001; 97: 3380–3389.

    Article  CAS  Google Scholar 

  24. Storek J, Viganego F, Dawson MA et al. Factors affecting antibody levels after allogeneic hematopoietic cell transplantation. Blood 2003; 101: 3319–3324.

    Article  CAS  Google Scholar 

  25. Storb R, Deeg HJ, Whitehead J et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med 1986; 314: 729–735.

    Article  CAS  Google Scholar 

  26. Herremans MM, Reimerink JH, Ras A et al. Evaluation of a poliovirus-binding inhibition assay as an alternative to the virus neutralization test. Clin Diagn Lab Immunol 1997; 4: 659–664.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Lim LCL, Lal M, Patnaik M . Simultaneous detection of IgG responses against 7 pneumococcal capsular polysaccharide serotypes (4, 6B, 9V, 14, 18C, 19F, 23F) utilizing a multi-analyte immunoarray assay. First Annual Meeting of the Federation of Clinical Immunology Societies, Boston. Clin Immunol 2001, 151–152.

  28. Peltola H, Kayhty H, Virtanen M et al. Prevention of Hemophilus influenzae type b bacteremic infections with the capsular polysaccharide vaccine. N Engl J Med 1984; 310: 1561–1566.

    Article  CAS  Google Scholar 

  29. Rosato MT, Jabbour AJ, Ponce RA et al. Simultaneous analysis of surface marker expression and cell cycle progression in human peripheral blood mononuclear cells. J Immunol Methods 2001; 256: 35–46.

    Article  CAS  Google Scholar 

  30. Schneider S, Bruns A, Moewes B et al. Simultaneous cytometric analysis of (auto)antigen-reactive T and B cell proliferation. Immunobiology 2002; 206: 484–495.

    Article  CAS  Google Scholar 

  31. Atkinson K, Farewell V, Storb R et al. Analysis of late infections after human bone marrow transplantation: role of genotypic nonidentity between marrow donor and recipient and of nonspecific suppressor cells in patients with chronic graft-versus-host disease. Blood 1982; 60: 714–720.

    CAS  Google Scholar 

  32. Winston DJ, Schiffman G, Wang DC et al. Pneumococcal infections after human bone marow transplantation. Ann Intern Med 1979; 91: 835–841.

    Article  CAS  Google Scholar 

  33. Kulkarni S, Powles R, Treleaven J et al. Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants [In Process Citation]. Blood 2000; 95: 3683–3686.

    CAS  Google Scholar 

  34. Whitney CG, Farley MM, Hadler J et al. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States. N Engl J Med 2000; 343: 1917–1924.

    Article  CAS  Google Scholar 

  35. Tauro S, Dobie D, Richardson G et al. Recurrent penicillin-resistant pneumococcal sepsis after matched unrelated donor (MUD) transplantation for refractory T cell lymphoma. Bone Marrow Transplant 2000; 26: 1017–1019.

    Article  CAS  Google Scholar 

  36. Clements ML, Miskovsky E, Davidson M et al. Effect of age on the immunogenicity of yeast recombinant hepatitis B vaccines containing surface antigen (S) or PreS2+S antigens. J Infect Dis 1994; 170: 510–516.

    Article  CAS  Google Scholar 

  37. Ward MM, Hall RP, Pisetsky DS . Serum interleukin-2 receptor responses to immunization. Clin Immunol Immunopathol 1990; 57: 120–124.

    Article  CAS  Google Scholar 

  38. Ilan Y, Nagler A, Shouval D et al. Development of antibodies to hepatitis B virus surface antigen in bone marrow transplant recipient following treatment with peripheral blood lymphocytes from immunized donors. Clin Exp Immunol 1994; 97: 299–302.

    Article  CAS  Google Scholar 

  39. Hata A, Asanuma H, Rinki M et al. Use of an inactivated varicella vaccine in recipients of hematopoietic-cell transplants. N Engl J Med 2002; 347: 26–34.

    Article  Google Scholar 

  40. Lum LG, Munn NA, Schanfield MS et al. The detection of specific antibody formation to recall antigens after human bone marrow transplantation. Blood 1986; 67: 582–587.

    CAS  Google Scholar 

  41. Lum LG, Noges JE, Beatty P et al. Transfer of specific immunity in marrow recipients given HLA-mismatched, T cell-depleted, or HLA-identical marrow grafts. Bone Marrow Transplant 1988; 3: 399–406.

    CAS  PubMed  Google Scholar 

  42. Shiobara S, Lum LG, Witherspoon RP et al. Antigen-specific antibody responses of lymphocytes to tetanus toxoid after human marrow transplantation. Transplantation 1986; 41: 587–592.

    Article  CAS  Google Scholar 

  43. Wahren B, Gahrton G, Linde A et al. Transfer and persistence of viral antibody-producing cells in bone marrow transplantation. J Infect Dis 1984; 150: 358–365.

    Article  CAS  Google Scholar 

  44. Wimperis JZ, Prentice HG, Karayiannis P et al. Transfer of functional humoral immune system in transplantation of T-lymphocyte depleted bone marrow. Lancet 1986; 8477: 339–343.

    Article  Google Scholar 

  45. Wimperis JZ, Brenner MK, Prentice HG et al. B cell development and regulation after T cell depleted marrow transplantation. J Immunol 1987; 138: 2445–2450.

    CAS  PubMed  Google Scholar 

  46. Wimperis JZ, Brenner MK, Drexler HG et al. Rapid recovery of helper activity following T cell depleted allogeneic marrow transplant. Clin Exp Immunol 1987; 69: 601–610.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Kwak LW, Taub DD, Duffey PL et al. Transfer of myeloma idiotype-specific immunity from an actively immunised marrow donor. Lancet 1995; 345: 1016–1020.

    Article  CAS  Google Scholar 

  48. Anderson Jr LD, Mori S, Mann S et al. Pretransplant tumor antigen-specific immunization of allogeneic bone marrow transplant donors enhances graft-versus-tumor activity without exacerbation of graft-versus-host disease. Cancer Res 2000; 60: 5797–5802.

    CAS  PubMed  Google Scholar 

  49. von Mensdorff-Pouilly S, Verstraeten AA, Kenemans P et al. Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin. J Clin Oncol 2000; 18: 574–583.

    Article  CAS  Google Scholar 

  50. MacLean GD, Reddish MA, Koganty RR et al. Antibodies against mucin-associated sialyl-Tn epitopes correlate with survival of metastatic adenocarcinoma patients undergoing active specific immunotherapy with synthetic STn vaccine. J Immunother Emphasis Tumor Immunol 1996; 19: 59–68.

    Article  CAS  Google Scholar 

  51. White CA, Weaver RL, Grillo-Lopez AJ . Antibody-targeted immunotherapy for treatment of malignancy. Annu Rev Med 2001; 52: 125–145.

    Article  CAS  Google Scholar 

  52. Black S, Shinefield H, Fireman B et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Pediatr Infect Dis J 2000; 19: 187–195.

    Article  CAS  Google Scholar 

  53. Gergen PJ, McQuillan GM, Kiely M et al. A population based serologic survey of immunity to tetanus in the United States. N Engl J Med 1995; 332: 761–766.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank study nurse Terri Cunningham, the staff of the FHCRC Long-Term Follow-Up Department and the patients who agreed to participate in the study. This study was supported by the National Institutes of Health Grants No. CA68496, AI46108, CA18221, CA18029, HL36444 and CA15704.

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Authors and Affiliations

  1. Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, USA

    J Storek, M A Dawson, B E Burman, T Stevens-Ayers, F Viganego, M E D Flowers, R P Witherspoon, D G Maloney & M Boeckh

  2. Specialty Laboratories, Santa Monica, CA, USA

    L C-L Lim

  3. National Institute of Public Health and Environment, Bilthoven, The Netherlands

    M M P T Herremans

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  1. J Storek
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  2. M A Dawson
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Correspondence to J Storek.

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Storek, J., Dawson, M., Lim, LL. et al. Efficacy of donor vaccination before hematopoietic cell transplantation and recipient vaccination both before and early after transplantation. Bone Marrow Transplant 33, 337–346 (2004). https://doi.org/10.1038/sj.bmt.1704336

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