title: Discrepant serological assays for Pneumococcus in renal transplant recipients - a prospective study.
abstract: Vaccine immunoprotection for Streptococcus pneumoniae is mediated by opsonizing antibodies targeting serotype-specific capsular polysaccharides. Quantitative antibody levels enzyme-linked immunosorbent assay (ELISA) and antibody-mediated opsonophagocytic assays (OPA) measure vaccine-induced protection; correlation of these assays in transplantation requires investigation. This study examines the laboratory assessment of antibody titers in vaccinated renal recipients. Streptococcus pneumoniae 19A is common in immunocompromised hosts and is represented in protein-conjugate vaccines (PCV) and polysaccharide vaccines (PSV). Antibodies to 19A in serial sera from 30 vaccinated renal transplant recipients were compared using ELISA and OPA assays. Subject titers were classified as protected or not by ELISA (>0.35 μg/ml) and OPA titer (>1:8). Antibody titers analyzed using McNemar's test indicate that protection measured by the two assays are not the same (P = 0.0078); simple linear regression of within-subject geometric means of 19A enzyme-linked immunosorbent assay (ELISA) antibody levels versus 19A opsonophagocytic assays (OPA) titers demonstrates significant correlation between the two assays (P < 0.001). Vaccination is increasingly important given increasing antimicrobial resistance worldwide. OPA and ELISA antibody assays do not correlate well using current values for protective immunity against the Pneumococcus in immunosuppressed transplant recipients. Future studies of vaccination in transplant recipients should evaluate protective antibody levels using both functional antibody assays and standard ELISA antibody titers. (ClinicalTrials.gov: NCT00307125).
authors.affiliation: Infectious Disease Division and MGH Transplant Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Jay A
authors.identifier: http://orcid.org/0000-0002-2671-3311
authors.initials: JA
authors.lastname: Fishman
authors.affiliation: Rho, Chapel Hill, NC, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Iklé
authors.affiliation: Infectious Disease Division and MGH Transplant Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wilkinson
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007118:Immunoassay / Q000379:methods; D016867:Immunocompromised Host; D016030:Kidney Transplantation / Q000009:adverse effects*; D011008:Pneumococcal Infections / Q000175:diagnosis* / Q000209:etiology* / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000627:therapeutic use; D011446:Prospective Studies; D012698:Serologic Tests / Q000379:methods*; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000302:isolation & purification*; D066027:Transplant Recipients
chemical_list: D000907:Antibodies, Bacterial; D022242:Pneumococcal Vaccines
keywords: antibody titer; antimicrobial resistance; enzyme-linked immunosorbent assay; opsonophagocytic assay; pneumococcal vaccine; protective immunity