BACKGROUND:Tetanus, diphtheria and acellular pertussis (Tdap) vaccination during pregnancy blunts the infant humoral immune response following primary immunization with pneumococcal conjugate vaccines (PCVs). While this effect typically resolves after the booster dose for most vaccine serotypes, its impact on nasopharyngeal carriage of pneumococcal vaccine serotypes remains unclear. METHODS:A total of 3298 nasopharyngeal swabs were collected from infants aged 6-30 months attending daycare centers in Belgium between 2018 and 2022, along with data on maternal Tdap vaccination status (clinicaltrials.gov identifier: NCT02888457). Streptococcus pneumoniae carriage and serotyping were assessed using culture-based methods (Quellung reaction) and molecular detection (LytA qPCR and serotype-specific qPCR). The association between Tdap vaccination during pregnancy and pneumococcal vaccine-related serotype carriage in infants was evaluated using logistic generalized estimating equation models. RESULTS:The PCV13-related serotype carriage was significantly higher in offspring of Tdap-vaccinated mothers during pregnancy compared to those born to Tdap-unvaccinated mothers. In addition, children who received a PCV10 or mixed PCV10/PCV13 schedule had significantly higher PCV13-related serotype carriage compared to those immunized exclusively with PCV13. No significant differences were observed in individual PCV13-related serotype carriage, except for a significantly higher carriage of the PCV13-related serotype 6C in children of Tdap-vaccinated mothers. No significant difference was found for non-vaccine serotype carriage. CONCLUSIONS:The Tdap vaccination during pregnancy was associated with increased pneumococcal vaccine-related serotype carriage in infants, though the clinical significance remains uncertain. Future studies integrating vaccine serotype carriage data with protective pneumococcal antibody levels are needed to inform future maternal and infant vaccination strategies.
Newborns rely on maternally transferred antibodies for immune protection, acquired across the placenta and through breast milk. Despite this importance, how closely the inherited antibody repertoire resembles the mother's has not been examined at the clonotypic level. We combined BCR-Seq with proteomic Ig-Seq to track SARS-CoV-2-specific antibody clonotypes across maternal blood, cord blood, and breast milk from six mRNA-immunized pregnant individuals. Vaccination earlier in gestation generated more diverse peak IgG repertoires but greater contraction before delivery, yielding fewer transferred clonotypes. Vaccination later in gestation produced more restricted peak repertoires, but more clonotypes persisted to delivery and transferred to cord. Infant cord was enriched for persistent, highly somatically mutated, and intraclonally diverse IgG clonotypes, consistent with preferential transfer of affinity-matured antibodies. In contrast, breast milk IgA repertoires were largely distinct from systemic repertoires and underwent substantial remodeling despite stable antigen titers. These findings define molecular determinants of passive immunity shaped by vaccination timing relevant to optimizing maternal immunization.
The WHO aims to eliminate hepatitis B virus (HBV) as a public health problem by 2030. HBV vaccination has reduced HBV incidence and mortality and is a cornerstone of the WHO elimination strategy. Belgium introduced universal infant HBV vaccination in 1999, with temporary catch-up vaccination for 12-year-olds, thereby covering all individuals born since 1987. This nationwide serosurvey assessed vaccine-induced hepatitis B surface antibody (anti-HBs) prevalence and natural HBV exposure in Belgium in 2020. We analyzed 4955 left-over samples from SARS-CoV-2 sero-epidemiology studies in 2020. Samples from ambulatory patients outside lockdown periods were tested for anti-HBs and hepatitis B core antibodies (anti-HBc) to evaluate vaccine-induced vs. natural exposure-derived anti-HBs responses. Samples were stratified by region, 10-year age band, and sex, and were weighted to reflect the Belgian population. Overall, 47.3
INTRODUCTION:Multiple SARS-CoV-2 vaccine types are available but the optimal platform for use in pregnancy remains unclear. This study compared humoral and cellular immune responses in blood and breastmilk following COVID-19 vaccination with different vaccine types during pregnancy. METHODS:In a prospective cohort study, pregnant individuals (85 % naïve for COVID-19) received at least one dose of either the adenoviral vector vaccine (AVV) ChadOx1-S (N = 17) or a messenger RNA vaccine (mRNAV) BNT162b2 (N = 42) or mRNA-1273 (N = 5) during pregnancy. Blood samples were taken at different timepoints before and after each vaccine dose, and at delivery. Breastmilk samples were collected up to 12 weeks postpartum. Follow-up continued until 28-35 days after postpartum mRNA booster vaccination (BNT162b2: N = 23; mRNA-1273: N = 25). The primary outcome was comparison of immune responses between the AVV and mRNAV group. RESULTS:mRNAV recipients showed significantly higher anti-RBD IgG titres, with greater avidity and neutralizing capacity, and stronger S1- and S2-specific CD154 CD4+ T-cell responses up to day 28 after the second vaccine dose. Cord blood from mRNAV recipients had significantly higher anti-RBD IgG and NAb titres at delivery compared to AV vaccinated individuals. After postpartum mRNA booster vaccination, immune responses were comparable between both groups. CONCLUSION:mRNA COVID-19 vaccination during pregnancy elicited more rapid and robust immune responses compared to AV vaccination. These findings suggest that mRNA vaccines may be preferable for emergency use during pregnancy and support their use in future maternal vaccine development and in pandemic preparedness recommendations. CLINICAL TRIAL REGISTRY:Clinicaltrials.govidentifier: NCT05618548.
Introduction Mpox remains endemic in the Democratic Republic of the Congo (DRC), with pregnant women at increased risk of severe disease and adverse outcomes. The WHO has called for data on mpox vaccination in high-risk groups, but no clinical trial has assessed the safety or immunogenicity of mpox vaccines in this population. The modified vaccinia Ankara–Bavarian Nordic (MVA-BN) vaccine, a third-generation, highly attenuated, non-replicating, live virus vaccine, has shown an excellent safety profile in adolescents and adults, including immunocompromised individuals, and is expected to be safe during pregnancy. Methods and analysis Pregnancy & Infancy mPox Vaccine study is a phase 3, open-label trial that aims to evaluate the safety, reactogenicity and immunogenicity of the MVA-BN vaccine in pregnant and postpartum women in Boende, the DRC, compared with adults of the POX-MVA-045 study ( NCT06549530 ) in DRC and Uganda. A total of 359 pregnant women (16–35 years old, in their second or third trimester of pregnancy) are being enrolled and randomised to receive the homologous MVA-BN vaccine regimen at a 28-day interval, with the first dose administered either before 32 weeks of gestation during pregnancy or within 72 hours postpartum (3:2 ratio randomisation). An additional, non-randomised group will receive post-exposure prophylaxis following confirmed mpox exposure. Primary immunogenicity analyses will assess the non-inferiority of neutralising antibody titres in pregnant women compared with those in non-pregnant adults. Primary safety analyses will compare reactogenicity in pregnant women to that observed in adults and safety in pregnant women to safety observed in adults and women vaccinated in the immediate postpartum period. Secondary analysis will evaluate neutralising antibody titres and total binding antibody concentrations over time for pregnant and postpartum women compared with adults and each other. Ethics and dissemination The trial integrates ancillary care pathways, local capacity building and formative workshops that co-developed research tools. Ethical approvals were obtained from institutional and national review boards in the DRC and Belgium. Results will be shared with local communities, national stakeholders and global health agencies. Trial registration number NCT06844500 & PACTR202511506487215.
Pregnancy and early infancy are periods of heightened vulnerability, with SARS-CoV-2 and influenza infections linked to adverse pregnancy outcomes, including preterm birth, and stillbirth. Maternal vaccination provides direct protection to mothers by active immunisation and to infants by passive immunisation. This scoping review mapped and described published literature on maternal vaccination against COVID-19, influenza, pertussis, and RSV, including which outcome domains were studied and the timing of vaccination examined, with the aim of identifying evidence gaps and supporting decision-makers in choosing priority areas for subsequent systematic review topics. A comprehensive literature search across multiple databases of studies published from January 2000 to October 2025 identified 636 publications (541 primary studies, 95 evidence syntheses). Studies on COVID-19 (261 studies, 45 reviews), influenza (161 studies, 29 reviews), pertussis (113 studies, 20 reviews), and RSV (20 studies, 11 reviews) were analysed. Substantial evidence on COVID-19, influenza, and pertussis vaccination on efficacy, effectiveness, safety and immunogenicity outcomes and the optimal timing of vaccination in relation to these outcomes during pregnancy is available. RSV vaccination evidence is limited. Updated systematic reviews would be helpful to clarify the optimal timing of COVID-19 vaccination and the effectiveness and safety of the coadministration of influenza and pertussis vaccines.
BACKGROUND:Tetanus, diphtheria, acellular pertussis (Tdap) vaccination in pregnancy protects newborns against pertussis, but the influence of gestational age (GA) at vaccination on maternal and neonatal immune profiles remains incompletely understood. This study aimed to characterize the effect of GA at Tdap vaccination on several antibody features during pregnancy and at birth, and to assess transplacental antibody transfer. METHODS:96 pregnant women received Tdap at different GAs between week 16 and 32 within a Belgian, prospective non-randomized controlled trial. Maternal blood was collected pre-vaccination, at multiple timepoints post-vaccination, and at delivery, alongside cord blood at birth. Tdap-specific total IgG and IgG subclasses were evaluated alongside Fc-mediated effector functions. Multivariate analyses were applied to define composite immune patterns. RESULTS:Post-vaccination, robust immune responses were observed across cohorts. At delivery, maternal total IgG and IgG1 against PRN, DT, and TT were higher with later vaccination, whereas other subclasses and functional responses were largely comparable. Cord blood profiles partially paralleled maternal patterns without reaching significance, and no significant effect of vaccination-to-delivery interval was detected. IgG transfer ratios generally declined with advancing GA; functional antibody transfer was largely unaffected. Multivariate analyses highlighted higher maternal antibody response profiles at delivery with later vaccination, while cord blood profiles were generally unaffected. CONCLUSION:Maternal Tdap antibody response profiles at delivery are influenced by vaccination timing, while neonatal antibody profiles at birth appear largely comparable within the limits of the study. These findings support current recommendations for Tdap administration between 16 and 32 weeks of gestation and underscore the flexibility of this window for routine antenatal care.
Abstract To better understand how pregnancy impacts humoral immunity, we conducted an in-depth longitudinal analysis of the kinetics and characteristics of vaccine responses in a prospective cohort of pregnant and non-pregnant women. Humoral immune responses observed among pregnant participants who received the mRNA-delivered SARS-CoV-2 vaccination, including their effector functions, were in some cases marginally lower than those among non-pregnant controls, while prior infection was associated with some potentiation in humoral responses. Importantly, vaccine-induced antibodies were efficiently transferred across the placenta, providing the fetus with passive immunity and underscoring the dual benefit of maternal vaccination for both mother and neonate against COVID-19. Delayed induction of spike-specific IgG4 following the primary two-dose vaccination series was observed in vaccine recipients, independent of pregnancy status. In a subset (n=6) of pregnant women whose spike-specific serum IgG repertoires were extensively profiled at the clonotypic level over time as part of another study, we proteomically identified secreted IgG clonotypes that had class-switched to IgG4. Matching of these clonotypes detected as IgG4 to those defined as SARS-CoV-2 spike-specific revealed that, while a minority of total clonotypes, they were elicited early in the immunization series and tended to be more highly mutated, more prevalent, and more persistent than clonotypes in the serological repertoire that were not detected as IgG4. Consistent with the increase in secreted vaccine-specific IgG4 over time, but its poorer placental transfer, these clonotypes were detected at greater levels in maternal but not cord blood at the time of delivery as compared to 28 days post the second vaccine dose. These findings indicate some impact in the kinetics, characteristics, and functions of the humoral response that may be associated with pregnancy-related immune modulation. Conservation of the late class-switch recombination to IgG4 that has previously been associated with mRNA-based SARS-CoV-2 vaccines raises questions about how different immunological states and vaccine components influence short- and long-term characteristics of the humoral immune response.
BACKGROUND:The Brighton Collaboration's GAIA initiative developed harmonised case definitions (CDs) to standardise safety monitoring for maternal immunisation studies globally. These definitions use levels of diagnostic certainty (LOC) to support use across settings with differing diagnostic capacity, but their real-world performance and applicability have remained uncertain. A 2023 review found that around half of GAIA CDs had not been evaluated and that several key outcomes performed poorly with high rates of cases that could not be classified at LOC 1-3 (achieving only LOC-4). METHODS:Ovid MEDLINE, EMBASE, and Web of Science databases were searched for research studies in English-language publications from 2014 to May 5th, 2025, that assessed the performance of the GAIA case definitions in routine care or research. Two reviewers independently screened studies and extracted data, resolving any discrepancies through consensus. The review protocol was registered with PROSPERO (CRD42025620433). RESULTS:Database searches identified 4260 records; after deduplication and two-stage screening, 10 studies including 42,587 cases were eligible. Three definitions had not been evaluated (ectopic pregnancy, postpartum endometritis, neurodevelopmental delay), and several others have only been assessed in high-income settings. While CDs for maternal death, neonatal death, and preterm birth performed well, others had high proportions of unclassifiable cases, achieving only LOC-4. Variability was seen with some studies able to classify 100% of potential cases, whilst others were only able to classify 50% at LOC 1-3. CONCLUSIONS:Although progress has been made in evaluating GAIA case definitions, challenges remain in understanding their applicability across settings and data sources. Variability likely reflects differences in setting-level resources, data availability and documentation quality, as well as limitations inherent to the definitions themselves, highlighting the need for targeted refinement and broader validation to support robust, standardised, and comparable maternal immunisation safety surveillance globally.
BACKGROUND:The COVID-19-pandemic prompted global vaccination campaigns, raising important questions about vaccine-induced immune responses in lactating women and the transfer of SARS-CoV-2-specific antibodies through human milk. This study investigated the presence of SARS-CoV-2-specific IgA and IgG antibodies in breastmilk for up to 6 months following COVID-19 vaccination and booster doses with either mRNA or adenoviral vector (AVV) vaccines. METHOD:The COVALAC-study was a prospective cohort study conducted in Belgium. Women were recruited between February and March 2021, followed for 180 days post-vaccination and 28 days post-booster. Breastmilk samples were collected at multiple timepoints and analyzed for IgA and IgG antibodies. Participants received either mRNA (BNT162b2, mRNA-127) or AVV (ChAdOx1 nCoV-19) vaccines. Antibody concentrations were measured using an in-house immunoassay, and analyses compared responses between vaccine types. RESULTS:Of the 115 participants, 40% received BNT162b2, 4.3% mRNA-1273, and 55.7% ChAdOx1-S as their primary vaccination. Of these, 31 participants received an mRNA booster (11 homologous, 20 heterologous boosters). IgA and IgG antibody levels were monitored pre- and post-vaccination, showing a stronger antibody response after mRNA vaccination compared to AVV, after roughly 14 days (IgA receptor binding domain [RBD] 1.13 BAU/mil; 0.61-1.67; IgG RBD 2.56 BAU/mil; 0.76-4.71, up to 1 month, for most antibodies. Both homologous and heterologous boosters further increased antibody titers (IgA RBD 0,85 BAU/ml; 1.09-1.72). CONCLUSION:COVID-19 vaccination during lactating induces SARS-CoV-2 specific IgA and IgG antibodies in human milk. Antibody levels were higher following mRNA vaccination compared to AVV vaccination, with booster doses enhancing these levels further.
Tetanus-diphtheria-acellular pertussis (Tdap) vaccination during pregnancy protects newborns from pertussis in the early months of life. Previous research indicated that Tdap vaccination during pregnancy may blunt Bordetella pertussis (B. pertussis)-specific antibody responses in infants following acellular (aP) and whole cell pertussis (wP) vaccination. However, the effect of preexisting antibodies on infants’ responses to diphtheria toxoid (DT), tetanus toxoid (TT) and B. pertussis antigens is less well-understood. This study aims to quantify the effect of preexisting anti-DT, anti-TT, and B. pertussis-specific antibody levels from Tdap vaccination during pregnancy on infants’ post-primary and post-booster responses to aP- and wP-containing vaccines. This retrospective analysis utilized data collected from a randomized controlled trial (NCT02408926) between 2015 and 2018. Pregnant women received Tdap vaccination between 27 and 36 weeks gestation. Their term infants were randomized to receive either a pentavalent DTwP-HB-Hib (wP) or a hexavalent DTaP-HB-Hib-IPV (aP) vaccine. Preexisting immunity was defined as the levels of anti-DT, anti-TT, anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), and anti-pertactin (PRN) IgG at month 2 (pre-vaccination). Blood samples were collected at birth, month 2, month 7 (following primary series vaccination at 2, 4, 6 months), month 18 (pre-booster), and month 19 (post booster). A total of 132 aP-vaccinated and 123 wP-vaccinated children completed this study. High levels of pre-vaccination antibody levels correlated with lower geometric mean ratios (GMRs) at post-primary and post-booster following wP- and aP-containing vaccination. This effect was observed consistently across all vaccine antigens following primary and booster doses. The clinical significance of this observation requires further investigation.
OBJECTIVES:To assess geographical variation in maternal measles antibody levels from birth to nine months of age, to inform recommendations for the timing of the first measles vaccine dose. METHODS:Stored infant serum samples from 11 countries taken at delivery and/or follow-up time points prior to measles vaccination (N=2845) were tested for measles plaque reduction neutralisation (PRNT) and measles, mumps, and rubella immunoglobulin G at a central laboratory. Antibody decay in infants was modelled using linear mixed effects models with participant-level random intercepts and random slopes. Proportions of infants with antibody concentrations above the clinical protection threshold (0.12 IU/mL) were estimated at each age. RESULTS:At birth, most (94%, 519/552) infants had PRNT ≥0.12 IU/mL, but geometric mean concentrations ranged from 0.32 IU/mL (Guatemala) to 1.60 IU/mL (Pakistan). There was no geographical variation in the decay rate of PRNT nor immunoglobulin G. Geometric mean PRNT fell below 0.12 IU/mL between ages 2.5 months (Guatemala) and 6.2 months (Pakistan). At age 6 months, <50% of infants had PRNT ≥0.12 IU/mL in all countries except Pakistan. CONCLUSIONS:Reliance on maternal antibodies for protection until age 9 months or later leaves most infants with insufficient direct protection against measles infection between ages 6-9 months.
BACKGROUND:Cell-mediated immunity (CMI), in addition to the humoral immune response, is crucial in clearing infections. Cytokines are important mediators of the immune system and play a role during pregnancy and childbirth. This study assesses circulating cytokine levels in peripartum maternal and cord blood samples at term and preterm delivery. MATERIALS AND METHODS:Samples from 37 mother-infant pairs from a previously conducted maternal immunization study were used to quantify levels of 6 cytokines [interferon (IFN)-γ, interleukin (IL)-10, IL-17A, IL-1β, IL-6 and tumor necrosis factor-α] using the Meso Scale Discovery® ultrasensitive S-plex assay. The effect of various factors on measured cytokine levels was determined. RESULTS:Weak to moderate correlations between maternal and cord blood cytokine levels were found. A trend for lower cytokine levels for preterm compared with term delivery was observed. The trend for lower cytokine levels was also seen for cesarean section compared with vaginal delivery and multiparous compared with primiparous women, but only in maternal serum samples. After correction for other variables, the effects of gestational age at delivery and parity were only significant for, respectively, IFN-γ and IL-6 in maternal serum. CONCLUSIONS:The assessment of circulating cytokine levels in mother-infant pairs at term and preterm deliveries provides a unique insight into the presence of cytokines in maternal and cord blood and their interplay at delivery. It also highlights the complexity of the maternal-fetal immune relationship and underscores the need for further investigation into the origin of cytokines in newborns and the impact of vaccination in pregnancy on CMI at delivery.
Health-related misinformation on social media may affect vaccination behavior, particularly among (soon-to-be) mothers. Research suggested different strategies to correct misinformation, but it is unclear which strategies work best for what group and in what situation. Addressing the call for more emotion-based debunking strategies, this study examined how text genre (narrative vs. expository) and harm presence (with vs. without harm-stressing messages) interact to affect emotional responses, and debunking efficacy in corrective texts about vaccination and reproductive health, specifically targeting pregnant or planning-to-be pregnant women (N = 432) with varying levels of vaccine skepticism. We further assessed social media engagement, and information-seeking intentions. In particular, harm presence was tested as a moderator in the relationship between text genre and emotional responses, which in turn, mediate outcomes such as engagement with corrective texts and further information-seeking intentions on social media. Results from an online experimental survey showed that, in general, corrective texts about COVID-19 vaccine misinformation were more effective in reducing misconceptions compared to control texts. For women not skeptical towards vaccination, narratives with harm-stressing messages (vs. no harm) induced most negative emotions, reducing debunking efficacy, social media engagement, and information-seeking intention. For women skeptical towards vaccination, narratives (vs. expository) elicited stronger negative emotions, irrespective of harm-stressing messages, leading to decreased debunking efficacy, social media engagement, and the intention to seek information. This study illuminates the importance of tailoring vaccination corrective texts for different vaccine skepticism groups, avoiding one-size-fits-all strategies and being mindful of strong negative emotions and their counter-persuasive impact.
ABSTRACT Streptococcus pneumoniae serotype 23B, a non-vaccine serotype, has shown an increasing prevalence and penicillin non-susceptibility among carriage and invasive pneumococcal disease (IPD) isolates. Recently, a novel penicillin non-susceptible genotype has emerged, named 23B1. In the framework of the Belgian pneumococcal carriage study, we studied the prevalence of 23B 0 /23B1 among 586 23B strains (2016–2022) in 172 day care centers from 6- to 30-month-old children and among 130 pediatric 23B IPD isolates (2007–2021). Pneumococci were whole genome sequenced to determine the capsular polysaccharide genotype and sequence type (ST). Antimicrobial susceptibility testing determined penicillin and amoxicillin MICs, as well as resistance to co-trimoxazole and levofloxacin. 23B carriage was stable during 2016 ̶ 2022 except in the 2020–2021 winter season when it increased. The proportion of genotype 23B1 compared to 23B 0 decreased from 2016 ̶ to 2022 but remained consistently higher than 23B 0 . In 2020–2021, an increase in the proportion of 23B1 was reflected in an overall increase in 23B carriage. All increases in 23B IPD cases were almost entirely driven by 23B1. The median penicillin MICs were significantly different for 23B 0 (0.03 mg/L) and 23B1 (0.25 mg/L). In 2021, increased intermediate levofloxacin susceptibility was noted in 23B. 23B1-associated ST2372 was the most prevalent ST in carriage and IPD during 2013–2022. We show that an increase in 23B carriage among children was paralleled in pediatric IPD in Belgium, reiterating the utility of pneumococcal surveillance in the day care population. Serotype 23B is reported worldwide as an important pediatric non-PCV13 serotype with reduced penicillin susceptibility, with 23B1 as the presumed driver for the increased prevalence. IMPORTANCE During the COVID-19 pandemic, the 23B serotype of Streptococcus pneumoniae has increased in prevalence in healthy carriage isolates from Belgian day care centers and pediatric (younger than 18 years of age) invasive pneumococcal disease (IPD) isolates. Additionally, an increase in penicillin non-susceptibility was also observed within this serotype. Recently, a genetic variant of 23B, named 23B1, was discovered, which is known to be related to decreased penicillin susceptibility. We showed that increases in 23B prevalence in healthy carriage and IPD cases always coincided with 23B1 expansions, leading to higher penicillin non-susceptibility rates. Increases in 23B in the day care population paralleled pediatric 23B IPD increases, indicating the vital role of day care monitoring of pneumococcal carriage. Countries should stay vigilant for prevalence increases in S. pneumoniae serotype 23B, given the decreased susceptibility to penicillin and co-trimoxazole of the 23B1 variant.
Pneumococcal conjugate vaccines (PCVs) reduce Streptococcus pneumoniae infection and carriage. After switching from PCV13 to PCV10 in 2015-2016, Belgium switched back to PCV13 in 2019. Building on our systematic monitoring of childhood nasopharyngeal carriage since 2016, here, we analyze the serotypes of S. pneumoniae and other pathogens in children attending daycare centers (DCCs) from 2018 to 2021. From the period of 2018-2019 to 2020-2021, we included a total of 2,741 nasopharyngeal swabs collected from children aged 6 to 30 months. We identified S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus and conducted serotyping and antimicrobial susceptibility assessments of S. pneumoniae strains using culture methods and real-time PCR. S. pneumoniae carriage was frequent and quite stable over the three study years. H. influenzae and M. catarrhalis were more frequently carried than S. pneumoniae. Frequency of all PCV13-serotypes together among S. pneumoniae carriers decreased significantly from 19.4% in 2018-2019 to 9.9% in 2020-2021 (p < .001), largely due to the decreased serotype 19A carriage. Resistance of pneumococcal strains to penicillin increased significantly over the three study years. Two years after the second switch to PCV13 in 2019, pneumococcal serotype 19A carriage decreased again significantly in Belgian children attending daycare centers.
Transfer of antibodies across the placenta provides critical early life protection for neonates against infection. Understanding factors influencing efficient transfer is vital for enhancing neonatal immunity and improving maternal vaccination strategies. Stored maternal and cord serum samples from studies in The Gambia, Guatemala, Mali, The Netherlands, Pakistan, Thailand, UK and Vietnam were processed for measles plaque reduction neutralisation titres (PRNT), and measles, mumps and rubella immunoglobulin G (IgG) (multiplex immunoassay) at a central laboratory (N = 557 pairs). Nutritional indicators (ferritin, soluble transferrin receptor, retinol binding protein) and total IgG, were measured in subsets of maternal serum. Transplacental transfer ratios (TPTRs) were calculated and factors associated with maternal IgG, cord IgG and TPTRs explored in multivariable regression. At delivery, most mothers (range 78 % Guatemala to 100 % Pakistan, Netherlands) and infants (range 86 % Guatemala to 100 % Netherlands, UK) had PRNT above the threshold of clinical protection (0.12 IU/mL). Maternal and cord antibody concentrations across diverse geographical settings were highly correlated. TPTRs were highest in high-income countries; geometric mean range 0.7 (Pakistan) to 2.2 (Netherlands), and were correlated across antigens. However, TPTRs varied widely within low/middle-income countries. In models adjusting for country, higher maternal total IgG was consistently associated with lower TPTR. In multivariable regression, lower iron status, indicated by increasing soluble transferrin receptor concentration, was significantly associated with lower TPTR for measles neutralising antibody. There is marked geographical variation in TPTRs, and following adjustment for this, measurable factors in maternal blood can inform estimates of transplacental transfer efficiency.
An optimally designed experiment reaches results quicker, at a lower cost, or with fewer observations and is therefore crucial in maximizing resource efficiency in research. In immunization studies, the primary goal is often to characterize antibody kinetics-the change in antibody concentration over time. However, nonlinear models for antibody kinetics present substantial challenges for study design, particularly the need to provide information on the parameters of interest. We propose a novel framework to facilitate the design of immunization studies using simple, understandable information. We assume that the mean antibody concentration follows the structural form of the beta density until reaching a plateau. Using the time and height of the maximum and the time and height of the plateau, we can uniquely determine the antibody kinetics curve. Optimal sampling schedules are determined using D-optimality, with D-efficiency used to compare designs. In a robustness analysis across 12 scenarios, we analyzed the framework's sensitivity to misspecification in the initial information. When misspecifying one parameter at a time, the median D-efficiencies exceeded 0.95 and the first quartiles were greater than or equal to 0.9 for all parameters, highlighting the robustness of the framework. Misspecification in the height of the plateau and time of the maximum affected the D-efficiency the most. The great advantage of the framework is that we only need intuitive information from the medical professionals to design an immunization study, in which determining the antibody kinetics is the main goal.