ABSTRACT
Young children and allogeneic hematopoietic cell transplantation (HCT) recipients respond poorly to polysaccharide antigens, rendering them susceptible to severe infections because of encapsulated bacteria. This study evaluated the responses of 127 HCT patients, median age 23.0 years, vaccinated with PNCRM7 and Haemophilus influenzae (HIB) conjugate, 2 conjugate vaccines highly immunogenic in healthy children. Median time to vaccination was 1.1 years after HCT. Sixty-two percent of patients responded to PNCRM7 (45 of 51 children, 34 of 76 adults, P < .001). Overall response to HIB was 86%, including 77% of PNCRM7 nonresponders. Although PNCRM7 response was adversely affected by older age (P < .001), individuals > or =50 years old responded significantly better if vaccinated following acquisition of specific minimal milestones of immune competence, CD4 >200/microL, IgG >500 mg/dL, PHA within 60% lower limit of normal (11 of 19 versus 0 of 8, P < .006). A similar trend was observed in patients with limited chronic graft-versus-host disease (cGVHD). In all patients, higher levels of circulating CD4(+)CD45RA cells correlated with improved PNCRM7 response. These data demonstrate that PNCRM7 is immunogenic in allogeneic HCT patients, including older adults, but suggest that vaccination at fixed intervals after HCT, irrespective of immune competence, may limit its effectiveness. Prospective, multicenter trials assessing the best strategy to administer this vaccine and its impact on pneumococcal infections following transplantation are warranted.
Subject(s)
Haemophilus Vaccines/administration & dosage , Hematopoietic Stem Cell Transplantation , Meningococcal Vaccines/administration & dosage , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/administration & dosage , Recovery of Function/drug effects , Adolescent , Adult , CD4 Lymphocyte Count , Child , Child, Preschool , Chronic Disease , Female , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Haemophilus Vaccines/immunology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Heptavalent Pneumococcal Conjugate Vaccine , Humans , Infant , Male , Meningococcal Vaccines/immunology , Middle Aged , Multicenter Studies as Topic , Pneumococcal Infections/immunology , Pneumococcal Infections/mortality , Pneumococcal Vaccines/immunology , Prospective Studies , Recovery of Function/immunology , Retrospective Studies , Transplantation, Homologous , VaccinationABSTRACT
The ability to reliably identify the peptides that can bind to MHC molecules is of practical importance for rapid vaccine development. Several computer-based prediction methods have been applied to study the interaction of MHC class I/peptide binding. Here we have compared the binding of peptides predicted by three algorithms (BIMAS, SYFPEITHI and Rankpep) to the binding of the peptides to HLA-A*0201 molecules in vitro, assessed using a MHC stabilization assay on live T2 cells. Fifty HLA-A*0201 peptides were selected from several target oncoproteins: Wilms' tumor protein (WT1), native and imatinib-mutated bcr-abl p210, JAK2 protein and Ewing's sarcoma fusion protein type 1. The sensitivity and specificity of BIMAS, SYFPEITHI and Rankpep respectively, were: 86%, and 82%; 75% and 73%; 64% and 82%. Combining two or more computer methods did not appear to significantly improve the predictive value.
