Having a common standardized assay has proven to be an effective tool for the establishment of a protective antibody threshold for pneumococcal disease12and now GBS has the potential to follow the same path. Successful completion of Tropanserin the interlaboratory study and demonstration that the assay was robust and transferable across laboratories, was the culmination of many necessary steps required by each of the laboratories, including, but not limited to, coordination of assay-specific training, reagent transfer, and microsphere preparation and qualification. CPS serotypes Ia, Ib, II, III, IV, and V. The within-laboratory intermediate precision, which included factors like the lot of coated beads, laboratory analyst, and day, was generally below 20% relative standard deviation (RSD) for all six Rabbit polyclonal to PITPNM1 serotypes, across all five laboratories. The cross-laboratory reproducibility was < 25% RSD for all six serotypes, which demonstrated the consistency of results across the different laboratories. Additionally, anti-CPS IgG concentrations for the 44-member human serum panel were established. The results of this study showed assay robustness and that the resultant anti-CPS IgG concentrations were reproducible across laboratories for the six GBS CPS serotypes when the standardized assay was used. KEYWORDS:Group B streptococcus, maternal, neonatal, correlate of protection, vaccines == Introduction == Group B streptococcus (GBS) is a major cause of septicemia and meningitis in young infants, affecting 12 in every 1000 live births.1It can present as early- (< 7 days) or late-onset disease (789 days) in the first 3 months of Tropanserin life and is associated with adverse neurodevelopmental outcomes in up to 50% of meningitis survivors.1It can also lead to intra-amniotic infection, bacteremia, and postpartum endometritis in pregnant women. The availability of a vaccine that could be given to pregnant women to provide direct protection for mothers and their infants through maternally transferred antibody is an urgent need. However, demonstrating efficacy for a GBS vaccine through disease endpoint efficacy trials would be logistically challenging, likely requiring enrollment of upwards of 80,000 participants, and several years to complete with significant operational challenges.2 An alternative approach, by identifying biomarkers that correlate with protection against disease, can facilitate the development and introduction of new vaccines via an immunological endpoint study, as is accepted for pneumococcal disease,3Haemophilus influenzaetype b disease,4and meningococcal disease.58An antibody threshold concentration for invasive pneumococcal disease based on serum anti-pneumococcal capsular polysaccharide (CPS) IgG was developed after protection had been demonstrated by the 7-valent9,10and 9-valent11conjugate vaccines in clinical efficacy studies. The aggregate IgG putative serocorrelate threshold was agreed by consensus to be 035 g/mL based on results from three trials. Key to arriving at this estimate was Tropanserin a standardized ELISA that was adopted by the World Health Organization (WHO) for pneumococcal vaccine development in order to combine data from the different trials and laboratories.12This internationally accepted standardized assay was transferred to multiple laboratories to facilitate measurement of IgG antibodies for serotype-specific pneumococcal CPS, and identification of a putative threshold of protection for pneumococcal disease. For GBS, high concentrations of naturally occurring serotype-specific maternal antibody to CPS are associated with a reduced risk of invasive disease in neonates.13Therefore, serum anti-CPS IgG concentration may be a relevant parameter to inform a reliable estimate of protection from invasive GBS disease. Over the last 40 years, 34 different quantitative assays have been described in the literature.14Several studies have established an association between maternal or Tropanserin infant anti-CPS IgG concentrations and protection against GBS disease in infants, with some studies even reporting a protective threshold.1519However, the variability in assay methods and the lack of a human serum reference standard have precluded the definition of a globally accepted antibody threshold associated with risk reduction of invasive GBS disease. Thus, consensus is growing that standardization of assays to quantify GBS anti-CPS IgG responses to permit comparisons across natural history and vaccine studies would represent a major milestone for the definition of protective antibody concentrations that could be linked to vaccine performance. A previously described multiplex immunoassay (MIA)20was validated to measure IgG concentrations for the six predominant CPS serotypes of GBS (Ia, Ib, II, III, IV, and V), which are responsible for > 98% of GBS disease cases worldwide,21and was adopted by the international Tropanserin GBS Consortium GASTON (Group B streptococcalAssaySTandardisatiON)22as the standardized assay. The assay will be used by members of GASTON to derive anti-CPS IgG concentrations from seroepidemiology studies and,.
