Abstract
Forty-seven patients (age range, 7 months–18 years)with malignant (38 cases) and nonmalignant (9 cases)disorders given an allogeneic or an autologous bone marrowtransplantation (BMT) were immunized with Haemophilusinfluenzae type b (Hib) polysaccharide–diphtheriatoxoid conjugate vaccine administered in a single dose at different timepoints after transplantation. Results were compared with those of 13healthy children matched for age and sex who received the sameimmunization schedule. Serum and saliva samples for measurement of totalIgG subclass and specific antibody levels were obtained from patientsand healthy controls before and 3 weeks after vaccination. Twenty-fiveof the 47 patients (53%) had a specific anti-Hib IgGresponse, while an effective IgA and IgM response was mounted by 23(49%) and 11 (23%) children,respectively. In the control group, 13 of 13 subjects mounted a specificIgG antibody production (P < 0.005 in comparison to thepatients' response rate), while an IgA and IgM response wasdemonstrated in 12 (92%; P < 0.01compared to transplanted patients) and 7 (54%;P < 0.05 in comparison to BMT recipients) children,respectively. Lapse of time from BMT to immunization was the mostimportant factor predicting antibody response, as proved by an effectiveincrease in prevaccination specific IgG levels in the majority ofpatients vaccinated after 2 years from transplant. Our data demonstratethat BMT recipients have a reduced capacity to mount an antibodyresponse to polysaccharide antigens compared to normal controls, evenwhen a protein-conjugated vaccine is employed. Since time aftertransplant is the major factor influencing the recovery of immunereactivity to polysaccharide antigens, the ontogeny of the B cellrepertoire seems to follow a predetermined sequential program ofdevelopment.
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REFERENCES
Robbins JB, Schneerson R, Pittman M: Haemophilus influenzae type b infections. In Bacterial Vaccines, R Germanier (ed). New York: Academic Press, 1984, pp 289–316
Ambrosino DM, Schreiber JR, Daum RS, Siber GR: Efficacy of human hyperimmune globulin in prevention of Haemopylus influenzae type b disease in infant rats. Infect Immunol 39:709–714, 1983
Schreiber JR, Barrus V, Cates KL, Siber GR: Functional characterization of human IgG; IgM and IgA antibody directed to the capsule of Haemophulis influenzae type b. J Infect Dis 153:8–16, 1986
Barrett DJ, Lee CG, Ammann AJ, Ayoub EM: IgG and IgM pneumococcal polysaccharide antibody responses in infants. Pediatr Res 18:1067–1071, 1984
Rijkers GT, Sanders LAM, Zegers BJM: Anti-capsular poliysaccharide antibody deficiency states. Immunodeficiency 5:1–21, 1993
Aucouturier P, Barra A, Intrator L: Long lasting IgG subclass and antibacterial polysaccharide deficiency after allogeneic bone marrow transplantation. Blood 70:779–785, 1987
Lum LG: The kinetics of immune reconstitution after human marrow transplantation. Blood 69:369–380, 1987
Voltarelli JC, Stites DP: Immunological monitoring of bone marrow transplantation. Diagn Immunol 4:171–193, 1986
Atkinson K: Reconstruction of the haemopoietic and immune systems after marrow transplantation. Bone Marrow Transplant 5:209–226, 1990
Velardi A, Cucciaioni S, Terenzi A, Quinti I, Aversa F, Grossi CE, Grignani F, Martelli MF: Acquisition of Ig isotype diversity after bone marrow transplantation in adults: A recapitulation of normal B cell ontogeny. J Immunol 141:815–820, 1988
Ljungman P, Cordonnier C, de Bock R, Einsele H, Engelhard D, Grundy J, Link H, Locasciulli A, Prentice G, Reusser P, Ribaud P: Immunization after bone marrow transplantation: results of a European survey and recommendations from the infectious diseases working party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 15:455–460, 1995
Avanzini A, Carrà AM, Maccario R, Zecca M, Pignatti P, Marconi M, Comoli P, Bonetti F, DeStefano P, Locatelli F: Antibody response to pneumococcal vaccine in children receiving bone marrow transplantation. J Clin Immunol 15:137–144, 1995
Winston DJ, Winston GH, Schiffman G, Champlin RE, Feig SA, Gale RP: Pneumococcal vaccination of recipients of bone marrow transplants. Arch Intern Med 143:1735–1737, 1983
Robbins JB, Schneerson R: Polysaccharide-protein conjugates: A new generation of vaccines. J Infect Dis 161:821–832, 1990
Ambrosino DM, Sood SK, Lee MC, Chen D, Collard HR, Bolon DL, Johnson C, Daum RS: IgG1, IgG2 and IgM responses to 2 Haemophilus influenzae type b conjugate vaccines in young infants. Pediatr Infect Dis J 11:855–859, 1992
Eskola J, Kayhty H, Takala AK, Peltola H, Ronnberg PR, Kela E, Pekkanen E, McVerry PH, Makela PH: A randomized, prospective field trial of a conjugate vaccine in the protection of infants and young children against invasive Haemophilus influenzae type b disease. N Engl J Med 323:1381–1387, 1990
Black SB, Shinefield HR, Fireman B, Hiatt R, Polen M, Vittinghoff E: Efficacy in infancy of oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine in a United States population of 61.080 children. Pediatr Infect Dis J 10:97–104, 1991
Santosham M, Wolff M, Reid R, Hohenboken M, Bateman M, Goepp J, Cortese M, Sack D, Hill J, Newcomer W: The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex. N Engl J Med 324:1767–1772, 1991
Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Besinger W, Buckner CD, Clift R, Doney K, Farewell V, Hansen J, Hill R, Lum L, Martin P, McGuffin R, Sanders J, STeward P, Sullivan K, Witherspoon R, Yee G, Thomas ED: Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft-versus-host disease after marrow transplantation for leukemia. N Engl J Med 314:729–735, 1986
Willemze R, Richel DJ, Falkenberg JHF, Hale G, Waldmann H, Zwaan FE, Fibbe WE: In vivo use of CAMPATH-1G to prevent graft-versus-host disease and graft rejection after bone marrow transplantation. Bone Marrow Transplant 9:255–261, 1992
Shulman HM, Sullivan KM, Weiden PL, Mc Donald GB, Striker GE, Sale GE, Hackman R, Tsoi M, Storb R, Thomas ED: Chronic graft-versus-host syndrome in man. Am J Med 69:204–217, 1980
Plebani A, Ugazio AG, Avanzini AM, Masimi P, Zonta L, Monafo V, Burgio GR: Serum IgG subclass concentration in healthy subjects at different ages: Age percentile charts. Eur J Pediatr 149:164–167, 1989
Avanzini AM, Bjorkander J, Soderstrom R, Soderstrom T, Schneerson R, Robbins JB, Hanson LA: Qualitative and quantitative analyses of the antibody response elicited by Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugates in adults with IgG subclass deficiencies and frequent infections. Clin Exp Immunol 96:54–58, 1994
Parkkali T, Kayhty H, Ruutu T, Volin L, Eskola J, Ruutu P: A comparison of early and late vaccination with Haemophilus influenzae type b conjugate and pneumococcal polysaccharide vaccines after allogenic BMT. Bone Marrow Transplant 18:961–967, 1996
Sesardic D, Corbel MJ: Testing for neutralising potential of serum antibodies to tetanus and diphtheria toxin. Lancet 340:737–739, 1992
Quinti I, Velardi A, Le Moli S, Guerra E, D'Amelio R, Mastrantonio, Martelli MF, Aiuti F: Antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation. J Clin Immunol 10:160–166, 1990
Barra A, Cordonnier C, Preziosi M-P, Intrator L, Hessel L, Fritzell B, Preud'homme JL: Immunogenicity of Haemophilus influenzae type b conjugate vaccine in allogenic bone marrow recipients. J Infect Dis 166:1021–1028, 1992
Guinan EC, Molrine DC, Antin JH, Lee MC, Weinstein HJ, Sallan SE, Parsons SK, Wheeler C, Gross W, McGarigle C, Blanding P, Schiffman G, Finberg RW, Siber GR, Bolon D, Wang M, Cariati S, Ambrosino DM: Polysaccharide conjugate vaccine responses in bone marrow transplant patients. Transplantation 57:677–684, 1994
Molrine DC, Guinan EC, Antin JH, Parson SK, Weinstein HJ, Wheeler C, McGarigle C, Blanding P, Phillips NR, Kinsella K, Deans K, Ciamarra A, Goorin A, Geroge S, Ambrosino DM: Donor immunization with Haemophilus influenzae type b (HIB)-comjugate vaccine in allogeneic bone marrow transplantation. Blood 87:3012–3018, 1996
Vavassori M, Maccario R, Moretta A, Comoli P, Wack A, Locatelli F, Lanzavecchia A, Maserati E, Dellabona P, Casorati G, Montagna D: Restricted TCR repertoire and long-term persistence of donor-derivered antigen-experienced CD4+ T cells in allogeneic bone marrow transplantation recipients. J Immunol 157:5739–5747, 1996
Kato S, Yabe H, Yabe M, Kimura M, Ito M, Tsuchida F, Tsuji K, Takahashi M: Studies on transfer of varicella-zoster-virus specific T-cell immunity from bone marrow donor to recipient. Blood 75:806–809, 1990
Boland GJ, Vlieger AM, Ververs C, Gast GC: Evidence for transfer of cellular and humoral immunity to cytomegalovirus from donor to recipient in allogeneic bone marrow transplantation. Clin Exp Immunol 88:506–511, 1992
Preud'homme JL, Hanson LA: IgG subclass deficiency. Immunodefic Rev 2:129–149, 1990
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Avanzini, M.A., Carrà, A.M., Maccario, R. et al. Immunization with Haemophilus influenzae Type b Conjugate Vaccine in Children Given Bone Marrow Transplantation: Comparison with Healthy Age-Matched Controls. J Clin Immunol 18, 193–201 (1998). https://doi.org/10.1023/A:1020578921706
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DOI: https://doi.org/10.1023/A:1020578921706