Abstract
Fifty-three pediatric patients given an allogeneic or an autologous bone marrow transplantation (BMT) were immunized with a polyvalent pneumococcal capsular polysaccharide vaccine (Pneumovax II). Vaccine was administered six months or more after BMT and the pneumococcal IgM, total IgG, and IgG subclasses levels were evaluated before and three weeks after immunization. Immunization promoted a significant rise in antibody serum levels (P<0.000001), and all children vaccinated more than two years after transplantation responded to pneumococcal polysaccharides, whereas only 20–30% and 50% of patients given BMT between six months and one year and one and two years, respectively, mounted an eifective antibody production (P<0.0001). In univariate analysis, lapse of time from BMT to vaccination, chronic graft-versus-host disease occurrence, and female sex influenced the response rate. However, in multivariate analysis, only time between marrow transplant and immunization was a powerful predictor of response. Interestingly, four of 11 patients with IgG2 deficiency before immunization normalized serum levels of this IgG subclass after the pneumococcal antigenic challenge. Our study suggests that time after transplant is the major factor influencing the recovery of immune reactivity to polysaccharide antigens. This seems to confirm the hypothesis that ontogeny of the B-cell repertoire follows a predetermined sequential program in which polysaccharide antigens are some of the last to evoke an antibody response.
Similar content being viewed by others
References
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
Keever CA, Small TN, Flomenberg N, Heller G, Pekle K, Black P, Pecora A, Gillio A, Kernan NA, O'Reilly RJ: Immune reconstitution following bone marrow transplantation: Comparison of recipients of T-cell depleted marrow with recipients of conventional marrow grafts. Blood 73:1340–1350, 1989
Witherspoon RP, Lum LG, Storb R: Immunologic reconstitution after human marrow grafting. Semin Haematol 21:2–10, 1984
Winston DJ, Schiffman G, Wang DC: Pneumococcal infections after human bone marrow transplantation. Ann Intern Med 91:835–841, 1979
Aucouturier P, Barra A, Intrator L: Long lasting IgG subclass and antibacterial polysaccharide deficiency after allogeneic bone marrow transplantation. Blood 70:1382–1390, 1987
Sheridan JF, Tutschka PJ, Sedmak DD, Copelan ED: Immunoglobulin G subclass deficiency and pneumococcal infection after allogeneic bone marrow transplantation. Blood 75:1583–1586, 1990
Rogers TR, Riches PG, Walker SA, Joshi R: Changes in immunoglobulin levels and implications for immunoglobulin therapy to prevent infection following bone marrow transplantation.In Clinical Uses of Intravenous Immunoglobulins, A Morrell, UE Nydegger (eds.). London, Academic Press, 1986, pp 107–115
Shulman HM, Sullivan KM, Weiden PL, McDonald 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 byHaemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugates in adults with IgG subclass deficiencies and frequent infections. Clin Exp Immunol 96:54–58, 1994
Leinonen M, Sakkinen A, Kalliokoski R, Luotonen J, Timonen M, Makela H: Antibody response to 14-valent pneumococcal capsular polysaccaride vaccine in preschool age children. Pediatr Infect Dis 5:39–44, 1986
Weibel RE, Vella PP, McLean AA, Woodhour AF, Davidson WL, Hilleman MR: Studies in human subjects of polyvalent pneumococcal vaccines. Proc Soc Exp Biol Med 156:144–150, 1977
Briles DE, Claflin JL, Schroer K, Forman C: Mouse IgG3 antibodies are highly protective against intravenous infections with type 3Streptococcus pneumoniae. Nature 294:88–90, 1981
Koskela M, Leinonen M, Haiva V, Timonen M, Makela H: First and second dose antibody responses to pneumococcal polysaccharide vaccine in infants. Pediatr Infect Dis 5:45–50, 1986
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
Lortan JE, Vellodi A, Jurges ES, Hugh-Jones K: Class- and subclass pneumococcal antibody levels and response to immunization after bone marrow transplantation. Clin Exp Immunol 88:512–519, 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
Giebink GS, Warkentin PI, Ramsay NKC, Kersey JH: Titers of antibody to pneumococci in allogeneic bone marrow transplant recipients before and after vaccination with pneumococcal vaccine. J Infect Dis 154:590–596, 1986
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
Mond JJ, Schaefer M, Smith J, Finkelman FD: Lyb-5-B cells of CBA/N mice can be induced to synthesize DNA by culture with insolubilized but not soluble anti-Ig. J Immunol 131:2107–2109, 1983
Khater M, Macai J, Genyea C, Kaplan J: Natural killer cell regulation of age-related and type-specific variations in antibody responses to pneumococcal polysaccharides. J Exp Med 164:1505–1515, 1986
Witherspoon RP, Storb R, Ochs HD, Flournoy N: 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 antihymocyte globulin treatment. Blood 58:360–368, 1981
Fernandez C, Muller G: Immunological unresponsiveness to thymus independent antigens: 2 functionally different genetic mechanisms of B cell unresponsiveness to dextran. J Exp Med 146:1663–1667, 1977
Andersson U: Regulation of antibody synthesis.In Immunology of the Neonate, GR Burgio, LA Hanson, AG Ugazio (eds). Berlin, Springer-Verlag, 1987, pp 37–50
Cohn DA: High sensitivity to androgens as a contributing factor in sex difference in the immune response. Arthritis Rheum 22:1218–1233, 1979
Brown M, Schiffman G, Rittenberg MB: Subpopulations of antibodies to phosphocholine in humans serum. J Immunol 132:1323–1328, 1984
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Avanzini, M.A., Carra, A.M., Maccario, R. et al. Antibody response to pneumococcal vaccine in children receiving bone marrow transplantation. J Clin Immunol 15, 137–144 (1995). https://doi.org/10.1007/BF01543105
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01543105