Pertussis toxin neutralizing antibody response after an acellular booster vaccination in Dutch and Finnish participants of different age groups

Pertussis incidence has increased in many countries and the disease occurs among all age groups, suggesting the need for booster immunizations through life. In addition to determining the concentration of anti-pertussis toxin (PT) antibodies, the ability of PT neutralizing antibodies (PTNAs) could be used to assess vaccine responses.Altogether 258 participants [7–10-year-old (N = 73), 11–15-year-old (N = 85), 20–35-year-old (N = 50) and 60–70-year-old (N = 50)] were included. Sera were collected before, one month, and one year after a single dose of a three pertussis component containing acellular pertussis vaccine. The adolescents were primed in childhood either by acellular or whole-cell vaccination. PTNA titres were determined by a Chinese hamster ovary cell assay and anti-PT IgG/IgA antibody concentrations by multiplex immunoassay.In all age groups, a significant increase in levels of PTNAs and anti-PT IgG was observed one month after vaccination and remained at least two-fold higher one year post-booster, in comparison to pre-booster. Young adults had the lowest response. The strongest increase in PTNAs was observed in participants who had ≥10 IU/mL concentration of anti-PT IgG antibodies pre-booster. At pre-booster, whole-cell-primed adolescents had higher PTNAs than acellular-primed peers (p = 0.047). One year post-booster, the Finnish whole-cell-primed adolescents had a higher level of PTNAs than acellular-primed adolescents (p = 0.049), however, this was not observed in Dutch adolescents. In conclusion, PTNAs increased after vaccination in all age groups, and the strongest increase was related to the presence of high pre-booster antibodies.</p

Enhanced Bordetella pertussisacquisition rate in adolescents during the 2012 epidemic in the Netherlands and evidence for prolonged antibody persistence after infection.

IntroductionIn 2012 a large epidemic of pertussis occurred in the Netherlands. We assessed pertussis toxin (PT) antibody levels in longitudinal serum samples from Dutch 10-18 year-olds, encompassing the epidemic, to investigate pertussis infection incidence.Methods: Blood was sampled in October 2011 (n = 239 adolescents), then 1 year (2012; n = 228) and 3 years (2014; n = 167) later. PT-IgG concentrations were measured by immunoassay and concentrations ≥50 IU/mL (seropositive) assumed indicative of an infection within the preceding year.Results: During the 2012 epidemic, 10% of participants became seropositive, while this was just 3% after the epidemic. The pertussis acquisition rate proved to be sixfold higher during the epidemic (97 per 1,000 person-years) compared with 2012-2014 (16 per 1,000 person-years). In 2012, pertussis notifications among adolescents nationwide were 228/100,000 (0.23%), which is at least 40 times lower than the seropositivity percentage. Remarkably, 17 of the 22 seropositive participants in 2011, were still seropositive in 2012 and nine remained seropositive for at least 3 years.Discussion: Longitudinal studies allow a better estimation of pertussis infections in the population. A PT-IgG concentration ≥50 IU/mL as indication of recent infection may overestimate these numbers in cross-sectional serosurveillance and should be used carefully

Robust Humoral and Cellular Immune Responses to Pertussis in Adults After a First Acellular Booster Vaccination

IntroductionTo reduce the pertussis disease burden, nowadays several countries recommend acellular pertussis (aP) booster vaccinations for adults. We aimed to evaluate the immunogenicity of a first adult aP booster vaccination at childbearing age.MethodsIn 2014, healthy adults aged 25–29 years (n = 105), vaccinated during infancy with four doses of whole-cell pertussis (wP) vaccine, received a Tdap (tetanus, diphtheria, and aP) booster vaccination. Blood samples were collected longitudinally pre-booster, 2 and 4 weeks, and 1 year and 2 years post-booster. Tdap vaccine antigen-specific antibody levels and memory B- and T-cell responses were determined at all time points. Antibody persistence was calculated using a bi-exponential decay model.ResultsUpon booster vaccination, the IgG levels specific to all Tdap vaccine antigens were significantly increased. After an initial rapid decline in the first year, PT-IgG antibody decay was limited (15%) in the second year post-booster. The duration of a median level of PT-IgG ≥20 IU/mL was estimated to be approximately 9 years. Vaccine antigen-specific memory B- and T-cell numbers increased and remained at high levels although a significant decline was observed after 4 weeks post-booster. However, Th1, Th2, and Th17 cytokine production remained above pre-booster levels for 2 years.ConclusionThe Tdap booster vaccination in wP-primed Dutch adults induced robust long-term humoral and cellular immune responses to pertussis antigens. Furthermore, PT-IgG levels are predicted to remain above the presumed protective cut-off for at least 9 years which might deserves further attention in evaluating the current recommendation to revaccinate women during every new pregnancy

Effect of Palivizumab Prophylaxis on Respiratory Syncytial Virus Infection in Very Preterm Infants in the First Year of Life in The Netherlands

Respiratory Syncytial Virus (RSV) poses a severe threat to infants, particularly preterm infants. Palivizumab, the standard preventive prophylaxis, is primarily utilized in high-risk newborns due to its cost. This study assessed palivizumab’s effectiveness in preventing RSV infections in predominantly very preterm infants during their first year of life. Serum samples from a prospective multicentre cohort study in the Netherlands were analyzed to assess RSV infection rates by measuring IgG levels against three RSV proteins: nucleoprotein, pre-fusion, and post-fusion protein. Infants were stratified based on gestational age (GA), distinguishing very preterm (≤32 weeks GA) from moderate/late preterm (>32 to ≤36 weeks GA). In very preterm infants, palivizumab prophylaxis significantly reduced infection rates (18.9% vs. 48.3% in the prophylaxis vs. non-prophylaxis group. Accounting for GA, sex, birth season, and birth weight, the prophylaxis group showed significantly lower infection odds. In infants with >32 to ≤36 weeks GA, the non-prophylaxis group (55.4%) showed infection rates similar to the non-prophylaxis ≤32-week GA group, despite higher maternal antibody levels in the moderate/late preterm infants. In conclusion, palivizumab prophylaxis significantly reduces RSV infection rates in very premature infants. Future research should explore clinical implications and reasons for non-compliance, and compare palivizumab with emerging prophylactics like nirsevimab aiming to optimize RSV prophylaxis and improve preterm infant outcomes

Responses to an acellular pertussis booster vaccination in children, adolescents, and young and older adults: A collaborative study in Finland, the Netherlands, and the United Kingdom

Background: Pertussis can lead to serious disease and even death in infants. Older adults are more vulnerable to complications as well. In high-income countries, acellular pertussis vaccines are used for priming vaccination. In the administration of booster vaccinations to different age groups and target populations there is a substantial between-country variation. We investigated the effect of age on the response to acellular pertussis booster vaccination in three European countries.Methods: This phase IV longitudinal intervention study performed in Finland, the Netherlands and the United Kingdom between October 2017 and January 2019 compared the vaccine responses between healthy participants of four age groups: children (7-10y), adolescents (11-15y), young adults (20-34y), and older adults (60-70y). All participants received a three-component acellular pertussis vaccine. Serum IgG and IgA antibody concentrations to pertussis antigens at day 0, 28, and 1 year were measured with a multiplex immunoassay, using pertussis toxin concentrations at day 28 as primary outcome. This trial is registered with ClinicalTrialsRegister.eu (2016-003,678-42).Findings: Children (n = 109), adolescents (n = 121), young adults (n = 74), and older adults (n = 75) showed high IgG antibody concentrations to pertussis toxin at day 28 with GMCs of 147 (95% CI 120-181), 161 (95% CI 132-196), 103 (95% CI 80-133), and 121 IU/ml (95% CI 94-155), respectively. A significant increase in GMCs for vaccine antigens in all age groups by 28 days was found which had decreased by 1 year. Differences in patterns of IgG GMCs at 28 days and 1 year post-vaccination did not have a consistent relationship to age. In contrast, IgA antibodies for all antigens increased with age at all timepoints.Interpretation: Acellular pertussis booster vaccination induces significant serum IgG responses to pertussis antigens across the age range which are not uniformly less in older adults. Acellular boosters could be considered for older adults to reduce the health and economic burden of pertussis.</p

Immunity against Neisseria meningitidis Serogroup C in the Dutch Population before and after Introduction of the Meningococcal C Conjugate Vaccine

Contains fulltext : 88187.pdf (publisher's version ) (Open Access)BACKGROUND: In 2002 a Meningococcal serogroup C (MenC) conjugate vaccine, with tetanus toxoid as carrier protein, was introduced in the Netherlands as a single-dose at 14 months of age. A catch-up campaign was performed targeting all individuals aged 14 months to 18 years. We determined the MenC-specific immunity before and after introduction of the MenC conjugate (MenCC) vaccine. METHODS AND FINDINGS: Two cross-sectional population-based serum banks, collected in 1995/1996 (n = 8539) and in 2006/2007 (n = 6386), were used for this study. The main outcome measurements were the levels of MenC polysaccharide(PS)-specific IgG and serum bactericidal antibodies (SBA) after routine immunization, 4-5 years after catch-up immunization or by natural immunity. There was an increasing persistence of PS-specific IgG and SBA with age in the catch-up immunized cohorts 4-5 years after their MenCC immunization (MenC PS-specific IgG, 0.25 microg/ml (95%CI: 0.19-0.31 microg/ml) at age 6 years, gradually increasing to 2.34 microg/ml,(95%CI: 1.70-3.32 microg/ml) at age 21-22 years). A comparable pattern was found for antibodies against the carrier protein in children immunized above 9 years of age. In case of vaccination before the age of 5 years, PS-specific IgG was rapidly lost. For all age-cohorts together, SBA seroprevalence (> or =8) increased from 19.7% to 43.0% in the pre- and post-MenC introduction eras, respectively. In non-immunized adults the SBA seroprevalence was not significantly different between the pre- and post-MenC introduction periods, whereas PS-specific IgG was significantly lower in the post-MenC vaccination (GMT, age > or =25 years, 0.10 microg/ml) era compared to the pre-vaccination (GMT, age > or =25 years, 0.43 microg/ml) era. CONCLUSION: MenCC vaccination administered above 5 years of age induced high IgG levels compared to natural exposure, increasing with age. In children below 14 months of age and non-immunized cohorts lower IgG levels were observed compared to the pre-vaccination era, whereas functional levels remained similar in adults. Whether the lower IgG poses individuals at increased risk for MenC disease should be carefully monitored. Large-scale introduction of a MenCC vaccine has led to improved protection in adolescents, but in infants a single-dose schedule may not provide sufficient protection on the long-term and therefore a booster-dose early in adolescence should be considered

Circulation of pertussis and poor protection against diphtheria among middle-aged adults in 18 European countries

Reported incidence of pertussis in the European Union (EU) and the European Economic Area (EEA) varies and may not reflect the real situation, while vaccine-induced protection against diphtheria and tetanus seems sufficient. We aimed to determine the seroprevalence of DTP antibodies in EU/EEA countries within the age groups of 40-49 and 50-59 years. Eighteen countries collected around 500 samples between 2015 and 2018 (N = 10,302) which were analysed for IgG-DTP specific antibodies. The proportion of sera with pertussis toxin antibody levels ≥100 IU/mL, indicative of recent exposure to pertussis was comparable for 13/18 countries, ranging between 2.7-5.8%. For diphtheria the proportion of sera lacking the protective level (</p

Elevated risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variants compared with Alpha variant in vaccinated individuals

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) break through infection- or vaccine-induced immunity is not well understood. We analyzed 28,578 sequenced SARS-CoV-2 samples from individuals with known immune status obtained through national community testing in the Netherlands from March to August 2021. We found evidence of an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared with the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14 to 59 days after complete vaccination compared with ≥60 days. In contrast to vaccine-induced immunity, there was no increased risk for reinfection with Beta, Gamma, or Delta variants relative to the Alpha variant in individuals with infection-induced immunity.</p

Pertussis Toxin Neutralizing Antibody Response After an Acellular Booster Vaccination in Dutch and Finnish Participants of Different Age Groups.

AbstractPertussis incidence has increased in many countries and the disease occurs among all age groups, suggesting the need for booster immunizations through life. In addition to determining the concentration of anti-pertussis toxin (PT) antibodies, the ability of PT neutralizing antibodies (PTNAs) could be used to assess vaccine responses.Altogether 258 participants [7-10-year-old (N = 73), 11-15-year-old (N = 85), 20-35-year-old (N = 50) and 60-70-year-old (N = 50)] were included. Sera were collected before, one month, and one year after a single dose of a three pertussis component containing acellular pertussis vaccine. The adolescents were primed in childhood either by acellular or whole-cell vaccination. PTNA titers were determined by a Chinese hamster ovary cell assay and anti-PT IgG/IgA antibody concentrations by multiplex immunoassay.In all age groups, a significant increase in levels of PTNAs and anti-PT IgG was observed one month after vaccination and remained at least two-fold higher one year post-booster, in comparison to pre-booster. Young adults had the lowest response. The strongest increase in PTNAs was observed in participants who had ≥10 IU/mL concentration of anti-PT IgG antibodies pre-booster. At pre-booster, whole-cell-primed adolescents had higher PTNAs than acellular-primed peers (p = 0.047). One year post-booster, the Finnish whole-cell-primed adolescents had a higher level of PTNAs than acellular-primed adolescents (p = 0.049), however, this was not observed in Dutch adolescents. In conclusion, PTNAs increased after vaccination in all age groups, and the strongest increase was related to the presence of high pre-booster antibodies