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Eight German and eight Italian children were observed during their first year in preschool. Cultural differences and similarities in play and behavior and sex differences are reported. Findings suggest that strategies that children use to enter kindergarten or a new group exist universally. (Author/RH)

Background: As COVID-19 becomes endemic, understanding antibody response and transfer during pregnancy is crucial to inform policy and vaccination schedules. While good immunogenicity has been shown from SARS-CoV-2 vaccines, few data are available demonstrating functional responses in pregnant populations and infants., Methods: A prospective, multi-site observational study was completed across 14 centers in England from April 23, 2020, to December 21, 2022. Demographic, COVID infection and vaccination data were collected. Maternal and cord blood samples were taken at delivery, with maternal and neonatal blood samples taken at 6 weeks for participants who had been infected or vaccinated. Antibody concentrations were measured using antibody-dependent complement deposition, antibody-dependent neutrophil phagocytosis, ACE2 inhibition and Roche and EuroImmun antibody binding assays at the UK Health Security Agency., Results: Maternal vaccination and infection both produced an antibody response in 100% of mothers and 93.8% and 92.9% of neonates, respectively, which persisted at 6 weeks in 95%. The strongest response was seen in mothers who were both vaccinated and infected. Anti-spike antibody response decreased almost 25-fold from first to third trimester vaccination (P=0.013). Placental transfer of antibodies post-infection showed varied results depending on the assay used, with higher transfer ratios observed in assays measuring Fc-mediated antibody effector functions and IgG-specific responses., Conclusions: Maternal vaccination is associated with good immunogenicity and successful antibody transfer to the neonate, particularly with vaccination in early pregnancy. Further study is needed to determine the mechanism by which the timing of vaccination affects antibody transfer. When measuring placental transfer of antibodies, consideration of the assay to use is essential., Competing Interests: All authors declare no conflict of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Bordetella pertussis epidemics persist as transmission remains unabated despite high acellular pertussis vaccination rates. BPZE1, a live attenuated intranasal pertussis vaccine, was designed to prevent B pertussis infection and disease. We aimed to assess the immunogenicity and safety of BPZE1 compared with the tetanus-diphtheria-acellular pertussis vaccine (Tdap)., Methods: In this double-blind, phase 2b trial at three research centres in the USA, healthy adults aged 18-50 years were randomly assigned (2:2:1:1) via a permuted block randomisation schedule to receive BPZE1 vaccination followed by BPZE1 attenuated challenge, BPZE1 vaccination followed by placebo challenge, Tdap followed by BPZE1 attenuated challenge, or Tdap followed by placebo challenge. On day 1, lyophilised BPZE1 was reconstituted with sterile water and given intranasally (0·4 mL delivered to each nostril), whereas Tdap was given intramuscularly. To maintain masking, participants in the BPZE1 groups received an intramuscular saline injection, and those in the Tdap groups received intranasal lyophilised placebo buffer. The attenuated challenge took place on day 85. The primary immunogenicity endpoint was the proportion of participants achieving nasal secretory IgA seroconversion against at least one B pertussis antigen on day 29 or day 113. Reactogenicity was assessed up to 7 days after vaccination and challenge, and adverse events were recorded for 28 days after vaccination and challenge. Serious adverse events were monitored throughout the study. This trial is registered with ClinicalTrials.gov, NCT03942406., Findings: Between June 17 and Oct 3, 2019, 458 participants were screened and 280 were randomly assigned to the main cohort: 92 to the BPZE1-BPZE1 group, 92 to the BPZE1-placebo group, 46 to the Tdap-BPZE1 group, and 50 to the Tdap-placebo group. Seroconversion of at least one B pertussis-specific nasal secretory IgA was recorded in 79 (94% [95% CI 87-98]) of 84 participants in the BPZE1-BPZE1 group, 89 (95% [88-98]) of 94 in the BPZE1-placebo group, 38 (90% [77-97]) of 42 in the Tdap-BPZE1 group, and 42 (93% [82-99]) of 45 in the Tdap-placebo group. BPZE1 induced broad and consistent B pertussis-specific mucosal secretory IgA responses, whereas Tdap did not induce consistent mucosal secretory IgA responses. Both vaccines were well tolerated, with mild reactogenicity and no serious adverse events related to study vaccination., Interpretation: BPZE1 induced nasal mucosal immunity and produced functional serum responses. BPZE1 has the potential to avert B pertussis infections, which ultimately could lead to reduced transmission and diminished epidemic cycles. These results should be confirmed in large phase 3 trials., Funding: ILiAD Biotechnologies., Competing Interests: Declaration of interests CK, KS, MT, PG, KR, and SN are equity holders in, and current or former employees of or consultants to, ILiAD Biotechnologies. VEM reports leadership of the Pearl institutional review. SN is a former employee of Novartis. AG has received honoraria from Sanofi Pasteur. CL holds patents on the BPZE1 vaccine (licensed to ILiAD Biotechnologies) and reports consulting fees from, and holds equity in, ILiAD Biotechnologies. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Pertussis vaccines have drastically reduced the disease burden in humans since their implementation. Despite their success, pertussis remains an important global public health challenge. Bordetella pertussis resurgence could be a result of greater surveillance combined with improved diagnosis methods, changes in Bordetella pertussis biology, vaccine schedules, and/or coverage. Additionally, mechanisms of protection conferred by acellular pertussis (aP) and whole-cell pertussis (wP) vaccines differ qualitatively. There are no clear immune correlates of protection for pertussis vaccines. Pertussis antigens can induce toxin neutralizing antibodies, block adherence or engage complement mediated phagocytic/bactericidal killing., Areas Covered: We reviewed the existing evidence on antibody-mediated serum bactericidal and opsonophagocytic activity and discussed the relevance of these functional antibodies in the development of next-generation pertussis vaccines., Expert Opinion: Current paradigm proposes that wP vaccines may confer greater herd protection than aP vaccines due to their enhanced clearance of bacteria from the nasopharynx in animal models. Functional antibodies may contribute to the reduction of nasal colonization, which differentiates aP and wP vaccines. Understanding the intrinsic differences in protective immune responses elicited by each class of vaccines will help to identify biomarkers that can be used as immunological end points in clinical trials.

The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants., (© 2022. The Author(s).)

Complement is a key component of functional immunological assays used to evaluate vaccine-mediated immunity to a range of bacterial and viral pathogens. However, standardization of these assays is complicated due to the availability of a human complement source that lacks existing antibodies acquired either through vaccination or natural circulation of the pathogen of interest. We have developed a method for depleting both IgG and IgM in 200 mL batches from pooled hirudin-derived human plasma by sequential affinity chromatography using a Protein G Sepharose column followed by POROS™ CaptureSelect™ IgM Affinity resin. The production of large IgG- and IgM-depleted batches of human plasma that retains total hemolytic and alternative pathway activities allows for improved assay standardization and comparison of immune responses in large clinical trials., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18-55 years ( NCT04324606 ). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.

Whooping cough is a re-emerging respiratory tract infection. It has become clear that there is a need for better understanding of protective immune responses and variation between Bordetella pertussis strains to aid the development of improved vaccines. In order to survive in the host, B. pertussis has evolved mechanisms to evade complement-mediated killing, including the ability to bind complement-regulatory proteins. Here we evaluate the variation in interactions with the complement system among recently isolated strains. Isolates whose genomes appear highly similar and cluster together on a SNP-based dendrogram were found to vary significantly in resistance to complement-mediated killing and in the deposition of C3b/iC3b, C5b-9 and C1 esterase inhibitor (C1-INH). The key role of Vag8 as a receptor for C1-INH was confirmed and its expression was shown to vary in a panel of isolates. A Vag8 knockout mutant showed increased sensitivity to complement-mediated killing. Antibodies in convalescent sera blocked C1-INH binding to B. pertussis and may play an important role in natural immunity.

Aim: To disclose the prevalence of adult "silent" coeliac disease in Denmark and Sweden., Experimental Design: 1573 Danish and 1866 Swedish healthy blood donors were screened for the presence of serum anti-gliadin antibodies (AGA) by enzyme-linked immunosorbent assay. AGA-positive serum samples were further analysed for IgA anti-endomysium antibodies (EmA) by indirect immunofluorescence microscopy., Main Results: The Danish donor population had a higher mean age than the Swedish (41.4 years versus 37.6 years) and a higher proportion of females (41% versus 32%), and had a lower mean level of AGA (17.3 units versus 20.6 units). Sixty-one (3.9%) Danish donors had AGA above the cut-off limit, and four of these also had positive EmA tests. Sixty (3.2%) Swedish donors had AGA above the cut-off limit, and five of these also had positive EmA. Coeliac pathology was proven by biopsy in all five coeliac disease-suspected Swedish donors. No small intestinal biopsy was performed in the coeliac disease-suspected Danish donors., Conclusions: Based upon the finding of EmA in AGA-positive serum samples, silent coeliac disease may be suspected in 1 per 394 Danish blood donors (2.5 per 1,000). A similar rate was proven in 1 per 373 Swedish blood donors (2.7 per 1,000), indicating no major differences in the prevalence of adult silent coeliac disease between the two neighbouring countries.

Of 771 children (381 Swedish and 390 Danish) investigated during 1972-1989 because of suspected coeliac disease (CD), 179 proved to have the disease. Surprisingly only 24 CD patients were Danish whereas 155 were Swedish, despite the very similar ethnic, geographical, and cultural backgrounds of the two populations. The Danish CD children were diagnosed at an older age (mean 5.5 versus 1.5 years). Breastfeeding habits were comparable. The estimated content of gliadin in the officially recommended diets of the two countries in 1987 differed substantially, the Swedish diet containing more than 40 times more gliadin than the Danish (4400 mg versus 100 mg) at the age of eight months, and four times more (3600 mg versus 900 mg) at the age of 12 months. Compared to the Swedish diet, the Danish infant diet contained significantly larger amounts of rye flour, which is low in gluten. The earlier introduction of food items with a high gluten content in the Swedish as compared with the Danish diet could be a possible explanation for the great difference in incidence and symptomatology of CD between the two populations.

Gastric emptying of meals of human milk or infant formula was studied in 17 healthy infants aged 4 weeks to 6 months using a marker dilution technique. In the 24 studies performed gastric emptying followed a biphasic pattern in 11 and a linear pattern in 12 studies. The average gastric half-emptying time for meals of human milk was 48 min, and for meals of infant formula 78 min. After 1 hour an average of 29.5 ml of human milk and 22.7 ml of infant formula per 0.1 m2 of body surface area had emptied from the stomach.