With birth, the newborn is transferred from a quasi-sterile environment to the outside world. At this time, the neonatal immune system is inexperienced and continuously subject to a process of development as it encounters different antigenic stimuli after birth. It is initially characterized by a bias toward T helper 2 phenotype, reduced T helper 1, and cytotoxic responses to microbial stimuli, low levels of memory, and effector T and B cells and a high production of suppressive T regulatory cells. The aim of this setting, during fetal life, is to maintain an anti-inflammatory state and immune-tolerance. Maternal antibodies are transferred during pregnancy through the placenta and, in the first weeks of life of the newborn, they represent a powerful tool for protection. Thus, optimization of vaccination in pregnancy represents an important strategy to reduce the burden of neonatal infections and sepsis. Beneficial effects of maternal immunization are universally recognized, although the optimal timing of vaccination in pregnancy remains to be defined. Interestingly, the dynamic exchange that takes place at the fetal-maternal interface allows the transfer not only of antibodies, but also of maternal antigen presenting cells, probably in order to stimulate the developing fetal immune system in a harmless way. There are still controversial effects related to maternal immunization including the so called “immunology blunting,” i.e., a dampened antibody production following infant's vaccination in those infants who received placentally transferred maternal immunity. However, clinical relevance of this phenomenon is still not clear. This review will provide an overview of the evolution of the immune system in early life and discuss the benefits of maternal vaccination. Current maternal vaccination policies and their rationale will be summarized on the road to promising approaches to enhance immunity in the neonate.

Selective IgA deficiency (SIgAD) is the most common human primary immune deficiency (PID). It is classified as a humoral PID characterized by isolated deficiency of IgA (less than 7 mg/dL but normal serum IgG and IgM) in subjects greater than 4 years of age. Intrinsic defects in the maturation of B cells and a perturbation of Th cells and/or cytokine signals have been hypothesized to contribute to SIgAD pathogenesis. The genetic basis of IgA deficiency remains to be clarified. Patients with SIgAD can be either asymptomatic or symptomatic with clinical manifestations including allergy, autoimmunity and recurrent infections mainly of the respiratory and gastrointestinal tract. Studies analyzing allergy on SIgAD patients showed prevalence up to 84%, supporting in most cases the relationship between sIgAD and allergic disease. However, the prevalence of allergic disorders may be influenced by various factors. Thus, the question of whether allergy is more common in SIgAD patients compared to healthy subjects remains to be defined. Different hypotheses support an increased susceptibility to allergy in subjects with SIgAD. Recurrent infections due to loss of secretory IgA might have a role in the pathogenesis of allergy, and vice versa. Perturbation of microbiota also plays a role. The aim of this review is to examine the association between SIgAD and atopic disease and to update readers on advances over time at this important interface between allergy and SIgAD.

Vaccination against COVID-19 is the most effective tool to protect both the individual and the community from this potentially life-threatening infectious disease. Data from phase-3 trials showed that two doses of the BNT162b2 vaccine were safe, immunogenic, and effective against COVID-19 in children aged 5–11 years. However, no surveys in real-life settings have been carried out in this age range. Here, we conducted a cross-sectional study to evaluate the short-term adverse reactions (ARs) and the rate of protection against infection of the BNT162b2 vaccine in children aged 5–11 years by the compilation of two surveillance questionnaires conceived using Google Forms. Five-hundred and ninety one children were included in the analysis. ARs were reported by 68.9% of the children, being mainly local. The incidence of systemic ARs, especially fever, was higher after the second dose. The incidence of infection after completing the immunization accounted for 13.6% of the children. COVID-19 symptoms reported were mild, with the exception of one case of pneumonia. Only 40% of infected participants needed to take medication to relieve symptoms, mostly paracetamol and NSAIDs, and none reported persistent symptoms. The Pfizer–BioNTech vaccine in children aged 5–11 years is safe and well tolerated. The mild clinical course of COVID-19 in immunized children confirmed the favorable risk–benefit ratio, encouraging parents to immunize their children.

Background: During the lockdown period caused by the SARS-CoV-2 pandemic, we monitored via online survey the trend of allergic symptoms and the therapeutic compliance in patients followed at our center. Material and methods: In June 2020, we selected children followed at the Allergy and Immunology Service of Umberto I Hospital, aged between 6 and 16 years old, diagnosed with asthma and/or rhinitis and sensitized to grass pollen or dust mite. We sent an email with 12 multiple-choice questions investigating several areas: type of disease and sensitization, recurrence of symptoms, medication use during lockdown compared to the same period of the previous year. Results: The results of 82 questionnaires showed that 17.8% of patients suffered from asthma, 24.4% from rhinitis, and 57.8% from both. Within the group of asthmatic children, most of them presented an improvement of their symptoms. Likewise, with regard to allergic rhinitis, most of them reported better clinical conditions. Regarding treatment, we observed a global decrease in the use of on-demand therapies (salbutamol, nasal corticosteroid, and antihistamine) for both pathologies. In addition, there was a reduction in the use of basal therapy for asthma and rhinitis from 2019 (23.3%) to 2020 (15.5%). Conclusions: Our data show a general trend of clinical improvement and a reduction in the use of on-demand and basal therapy in allergic children during the lockdown.

Starting from the “Hygiene Hypothesis” to the “Microflora hypothesis” we provided an overview of the symbiotic and dynamic equilibrium between microbiota and the immune system, focusing on the role of dysbiosis in atopic march, particularly on allergic rhinitis. The advent of deep sequencing technologies and metabolomics allowed us to better characterize the microbiota diversity between individuals and body sites. Each body site, with its own specific environmental niches, shapes the microbiota conditioning colonization and its metabolic functionalities. The analysis of the metabolic pathways provides a mechanistic explanation of the remote mode of communication with systems, organs, and microflora of other body sites, including the ecosystem of the upper respiratory tract. This axis may have a role in the development of respiratory allergic disease. Notably, the microbiota is significant in the development and maintenance of barrier function; influences hematopoiesis and innate immunity; and shows its critical roles in Th1, Th2, and Treg production, which are necessary to maintain immunological balance and promote tolerance, taking part in every single step of the inflammatory cascade. These are microbial biotherapy foundations, starting from probiotics up to postbiotics and parabiotics, in a still-ongoing process. When considering the various determinants that can shape microbiota, there are several factors to consider: genetic factors, environment, mode of delivery, exposure to antibiotics, and other allergy-unrelated diseases. These factors hinder the engraftment of probiotic strains but may be upgradable with postbiotic and parabiotic administration directly on molecular targets. Supplementation with postbiotics and parabiotics could represent a very exciting perspective of treatment, bypassing probiotic limitations. At present, this avenue remains theoretical and to be explored, but it will certainly be a fascinating path to follow.

(1) Background: Preterm birth exposes the infant to the known risk factors for atopic diseases. We aimed to study the neonatal risk factors and to describe the clinical manifestations of atopy, including the march of symptoms, in a cohort of preschool children born preterm. (2) Methods: We enrolled neonates with gestational age < 32 weeks or birth weight < 1500 g. We classified patients in cases and controls according to the presence of at least one atopic manifestation. (3) Results: We observed 72 cases and 93 controls. Multivariate models showed that the administration of more than one cycle of antibiotics (B 0.902, p = 0.026) and gestational diabetes (B 1.207, p = 0.035) influence the risk of atopy in babies born preterm. In addition, risk of atopic dermatitis was influenced by gestational age < 29 weeks (B −1.710, p = 0.025) and gestational diabetes (B 1.275, p = 0.027). The risk of wheeze was associated with familiarity for asthma (B 1.392, p = 0.022) and the administration of more than one cycle of antibiotics (B 0.969, p = 0.025). We observed a significant reduction in the rate of atopic manifestation after 2 years of life (33.9% vs. 23.8%, p < 0.05). (4) Conclusions: Modifiable (gestational diabetes, antibiotics use) and unmodifiable (familiarity for asthma) conditions influence the risk of atopy in babies born preterm. Extreme prematurity reduces the risk of atopic dermatitis. Preterm babies showed a peculiar atopic march.