Comparability of antibody response to a booster dose of 7-valent pneumococcal conjugate vaccine in infants primed with either 2 or 3 doses

In this cohort study we compared IgG antibody levels between infants immunized with 7-valent CRM197-conjugated pneumococcal vaccine (PCV-7) at 2,4 and 11 months and at 2, 3, 4 and 11 months of age,as measured by double adsorption ELISA. Pre- and post-booster levels following the 2 + 1 - and 3 + 1-dose schedule were comparable for 5 out of 7 serotypes except for serotypes 6B and 19F. The proportion of children reaching post-booster antibody thresholds were comparable except for 6B (>= 1.0 mu g/ml and >= 5.0 mu g/ml) and 19F (>= 5.0 mu g/ml). Surveillance studies are warranted for vaccine impact on 6B and 19F disease cases after reduced-dose PCV-7 schedules. (C) 2009 Elsevier Ltd. All rights reserved

Opsonic phagocytosis in chronic obstructive pulmonary disease is enhanced by Nrf2 agonists

Rationale: Previous studies have identified defects in bacterial phagocytosis by alveolar macrophages (AM) in patients with chronic obstructive pulmonary disease (COPD) but the mechanisms and clinical consequences remain incompletely defined. Objectives: To examine the effect of COPD on AM phagocytic responses and identify the mechanisms, clinical consequences and potential for therapeutic manipulation of these defects. Methods: We isolated alveolar macrophages (AM) and monocyte-derived macrophages (MDM) from a cohort of COPD patients and controls within the MRC COPD-MAP consortium and measured phagocytosis of bacteria in relation to opsonic conditions and clinical features. Measurements and Main Results: COPD AM and MDM have impaired phagocytosis of S. pneumoniae. COPD AM have a selective defect in uptake of opsonized bacteria, despite the presence of anti-pneumococcal antibodies in bronchoalveolar lavage, not observed in MDM or healthy donor’s AM. AM defects in phagocytosis in COPD are significantly associated with exacerbation frequency, isolation of pathogenic bacteria and health related quality of life scores. Bacterial binding and initial intracellular killing of opsonized bacteria in COPD AM was not reduced. COPD AM have reduced transcriptional responses to opsonized bacteria, including cellular stress responses that include transcriptional modules involving antioxidant defenses and Nrf2-regualted genes. Agonists of the cytoprotective transcription factor Nrf2 (sulforaphane and Compound) reverse defects in phagocytosis of S. pneumoniae and non-type able Haemophilus influenzae by COPD. Conclusions: Patients with COPD have clinically relevant defects in opsonic phagocytosis by AM, associated with impaired transcriptional responses to cellular stress, which are reversed by therapeutic targeting with Nrf2 agonists

Multilaboratory Comparison of Pneumococcal Multiplex Immunoassays Used in lmmunosurveillance of Streptococcus pneumoniae across Europe

Surveillance studies are required to estimate the impact of pneumococcal vaccination in both children and the elderly across Europe. The World Health Organization (WHO) recommends use of enzyme immunoassays (EIAs) as standard methods for immune surveillance of pneumococcal antibodies. However, as levels of antibodies to multiple serotypes are monitored in thousands of samples, a need for a less laborious and more flexible method has evolved. Fluorescent-bead-based multiplex immunoassays (MIAs) are suitable for this purpose. An increasing number of public health and diagnostic laboratories use MIAs, although the method is not standardized and no international quality assessment scheme exists. The EU Pneumo Multiplex Assay Consortium was initiated in 2013 to advance harmonization of MIAs and to create an international quality assessment scheme. In a multilaboratory comparison organized by the consortium, agreement among nine laboratories that used their own optimized MIA was assessed on a panel of 15 reference sera for 13 pneumococcal serotypes with the new WHO standard 007sp. Agreement was assessed in terms of assay accuracy, reproducibility, repeatability, precision, and bias. The results indicate that the evaluated MIAs are robust and reproducible for measurement of vaccine-induced antibody responses. However, some serotype-specific variability in the results was observed in comparisons of polysaccharides from different sources and of different conjugation methods, especially for serotype 4. On the basis of the results, the consortium has contributed to the harmonization of MIA protocols to improve reliability of immune surveillance of Streptococcus pneumoniae

The development of a bead-based multiplex immunoassay for the detection of IgG antibodies to CMV and EBV.

Latent infection with Cytomegalovirus (CMV) or Epstein-Bar virus (EBV) is associated with compromised immune responses. The commercially available ELISA-kits provide a semi-quantitative or qualitative detection of IgG antibodies against either CMV or EBV. To reduce the amount of sample needed and improve throughput and range of quantitation compared to ELISAs, a multiplex immunoassay (MIA) for the simultaneous quantitative detection of antibodies against CMV and two antigens of EBV (EBV capsid antigen (EBV-VCA) and EBV nuclear antigen 1 (EBNA-1)) was developed and standardized. Our assay shows a good correlation with the separate ELISAs, has a high specificity and is much more sensitive than the ELISAs. The MIA allows faster analysis of samples and can be combined with the MIA for detection of antibodies to measles, mumps, rubella and varicella zoster (MMRV) as published previously. In conclusion, the CMV-EBV MIA is a reliable assay that allows for more efficient detection of specific antibodies to CMV and EBV. This MIA therefore is especially useful for large-scale surveillance studies

The development of a bead-based multiplex immunoassay for the detection of IgG antibodies to CMV and EBV.

Latent infection with Cytomegalovirus (CMV) or Epstein-Bar virus (EBV) is associated with compromised immune responses. The commercially available ELISA-kits provide a semi-quantitative or qualitative detection of IgG antibodies against either CMV or EBV. To reduce the amount of sample needed and improve throughput and range of quantitation compared to ELISAs, a multiplex immunoassay (MIA) for the simultaneous quantitative detection of antibodies against CMV and two antigens of EBV (EBV capsid antigen (EBV-VCA) and EBV nuclear antigen 1 (EBNA-1)) was developed and standardized. Our assay shows a good correlation with the separate ELISAs, has a high specificity and is much more sensitive than the ELISAs. The MIA allows faster analysis of samples and can be combined with the MIA for detection of antibodies to measles, mumps, rubella and varicella zoster (MMRV) as published previously. In conclusion, the CMV-EBV MIA is a reliable assay that allows for more efficient detection of specific antibodies to CMV and EBV. This MIA therefore is especially useful for large-scale surveillance studies

Lagging Immune Response to Serotype b (Hib) Conjugate Vaccine after the Primary Vaccination with Hib of Infants in The Netherlands.

In 1993, a Haemophilus influenzae serotype b (Hib) conjugate vaccine was introduced in the Dutch national immunization program, resulting in a sharp decrease in invasive Hib disease. We used a population-based set of serum samples collected in the Netherlands in 2006-2007 (Pienter-II, 5696 sera) to assess the concentration of antibodies to the capsular polysaccharide of Hib, and compared the results with those obtained from a similar set collected in 1995-1996 (Pienter-I, 7837 sera). Post-primary vaccination serum samples from children aged 6-11 months from the Pienter-II study contained approximately 4-fold lower anti-Hib antibody concentrations than samples from children from the Pienter-I study. No such difference was found in post-booster samples from children older than 11 months of age. In Pienter-II, the proportion of children aged 6-11 months with anti-Hib antibody concentrations below the putative protective concentration of 0.15 µg/mL was 30%, which is significantly higher than in the Pienter-I study (12%). Fewer children in the Pienter-II group developed antibodies able to kill Hib in a serum bactericidal assay compared to the Pienter-I children. The cause of the lagged response in Pienter-II children remain uncertain, but lack of natural boosting, interference by the acellular pertussis vaccine, combining vaccines and acceleration of the schedule may have contributed

Levels and functionality of antibodies after pneumococcal conjugate vaccine in schedules with different timing of the booster dose

AbstractThe seven-valent pneumococcal conjugate vaccine (PCV7) has been introduced in most high-income countries, although with differences in age, timing and number of primary doses before 6 months of age and presence and timing of a booster vaccination. The objective was to determine and compare the IgG antibody levels and functionality of IgG responses (avidity and opsonophagocytoses) at 1 and 2 years of age following 2 primary doses with a booster at 11 or 24 months of age.Children received PCV7 at 2 and 4 months (2-dose group), or at 2, 4 and 11 months (2+1-dose group), or no PCV7 (controls) before 1 year of age. All children received a PCV7 dose at 24 months of age.At the age of 12 months, the 2+1-dose group had higher IgG levels and functional antibody levels, compared to the 2-dose group for all serotypes, but at 25 months the difference between the 2-dose and 2+1-dose groups had disappeared for most serotypes. The kinetics of opsonophagocytic antibodies were in line with the specific IgG antibody levels for most serotypes, although differences between the 2-dose and the 2+1-dose group were more pronounced in OPA activity as compared to the IgG levels especially at the age of 24 months.Delaying the booster dose from 11 months to 24 months after 2 primary doses resulted in significantly higher OPA GMTs one month after the booster dose. This must, however, be balanced against the risk of leaving children unboosted between the age of 11 and 24 months at a time when disease risk is still high. Local decisions about the timing of a booster dose should also take into account vaccine coverage and the indirect herd effect in a well vaccinated population.Trial registration clinicaltrials.gov Identifier: NCT00189020

Serotype-Specific IgG Antibody Waning after Pneumococcal Conjugate Primary Series Vaccinations with either the 10-Valent or the 13-Valent Vaccine.

The two currently available ten- and thirteen-valent pneumococcal conjugate vaccines (PCV10 and PCV13) both induce serotype-specific IgG anti-polysaccharide antibodies and are effective in preventing vaccine serotype induced invasive pneumococcal disease (IPD) as well as in reducing overall vaccine-serotype carriage and transmission and thereby inducing herd protection in the whole population. IgG levels decline after vaccination and could become too low to prevent carriage acquisition and/or pneumococcal disease. We compared the levels of 10-valent (PCV10) and 13-valent (PCV13) pneumococcal vaccine induced serum IgG antibodies at multiple time points after primary vaccinations. Data from two separate studies both performed in the Netherlands in infants vaccinated at 2, 3, and 4 months of age with either PCV10 or PCV13 were compared. Antibody levels were measured at 5, 8, and 11 months of age, during the interval between the primary immunization series and the 11-months booster dose. Serotype-specific IgG levels were determined by multiplex immunoassay. Although antibody kinetics showed significant variation between serotypes and between vaccines for the majority of the 10 shared serotypes, i.e., 1, 5, 7F, 9V, 14, 18C, and 23F, antibody concentrations were sufficiently high for both vaccines, immediately after the primary series and throughout the whole period until the booster dose. In contrast, for serotypes 4 and 19F in the PCV10 group and for serotypes 4 and 6B in the PCV13 group, IgG antibody concentrations already come within reach of the frequently used seroprotection level of 0.35 μg/mL immediately after the primary series at the five month time point and/or at eight months. This paper addresses the importance of revealing differences in serotype-specific and pneumococcal vaccine-dependent IgG antibody patterns during the interval between the primary series and the booster dose, an age period with a high IPD incidence. Trial registration: www.trialregister.nl NTR3069 and NTR2316