Mutations in two genes can result in activated PI3Kδ syndrome (APDS), a rare immunodeficiency disease with limited therapeutic options. Seletalisib, a potent, selective PI3Kδ inhibitor, was evaluated in patients with APDS1 and APDS2. In the phase 1b study (European Clinical Trials Database 2015-002900-10) patients with genetic and clinical confirmation of APDS1 or APDS2 received 15–25 mg/d seletalisib for 12 wk. Patients could enter an extension study (European Clinical Trials Database 2015-005541). Primary endpoints were safety and tolerability, with exploratory efficacy and immunology endpoints. Seven patients (median age 15 years; APDS1 n = 3; APDS2 n = 4) received seletalisib; five completed the phase 1b study. For the extension study, four patients entered, one withdrew consent (week 24), three completed ≥84 wk of treatment. In the phase 1b study, patients had improved peripheral lymphadenopathy (n = 2), lung function (n = 1), thrombocyte counts (n = 1), and chronic enteropathy (n = 1). Overall, effects were maintained in the extension. In the phase 1b study, percentages of transitional B cells decreased, naive B cells increased, and senescent CD8 T cells decreased (human cells); effects were generally maintained in the extension. Seletalisib-related adverse events occurred in four of seven patients (phase 1b study: hepatic enzyme increased, dizziness, aphthous ulcer, arthralgia, arthritis, increased appetite, increased weight, restlessness, tendon disorder, and potential drug-induced liver injury) and one of four patients had adverse events in the extension (aphthous ulcer). Serious adverse events occurred in three of seven patients (phase 1b study: hospitalization, colitis, and potential drug-induced liver injury) and one of four patients had adverse events in the extension (stomatitis). Patients with APDS receiving seletalisib had improvements in variable clinical and immunological features, and a favorable risk–benefit profile was maintained for ≤96 wk. Key Points Seletalisib, a PI3Kδ inhibitor, was evaluated in seven patients with APDS1 and APDS2. Following treatment, patients had improvements in clinical and immunological features. Seletalisib had a favorable risk–benefit profile in a phase 1b study up to 96 wk.

Background: We have previously reported that an early initiation of highly active antiretroviral therapy (HAART) in HIV-1 vertically infected children enhanced the function of memory B-cells gained during childhood routine vaccinations. On the other hand, a significant waning of immunity was observed for patients with a late treatment. In this follow-up study, we report data from a sample of patients in our cohort including late-treated patients being revaccinated with routine childhood vaccines. Methods: The levels of serum antibodies and cellular immunity were measured by antigen-specific enzyme-linked immunosorbent assay and B-cell ELISpot. Moreover, flow cytometry on the frequencies of mature-activated (CD10−CD21−) and double-negative (CD27–IgD–) B-cells as hallmarks of immune activation and immune senescence, respectively, was performed for all patients. Results: Reduced protective humoral immunity and cellular immunity to routine childhood vaccines was observed in late-treated patients. Moreover, we found that timing of HAART related with the frequencies of mature activated and double negative. Conclusions: Altogether the data presented in this follow-up study reenforce the importance for an early start of HAART in HIV-1 vertically infected individuals and suggest that timing of HAART is a fundamental factor to take into account for vaccination design in this population.

Routine vaccination is among the most effective clinical interventions to prevent diseases as it is estimated to save over 3 million lives every year. However, the full potential of global immunization programs is not realised because population coverage is still suboptimal. This is also due to the inadequate immune response and paucity of informative correlates of protection upon immunization of vulnerable individuals such as newborns, preterm infants, pregnant women, and elderly individuals as well as those patients affected by chronic and immune compromising medical conditions. In addition, these groups are undervaccinated for a number of reasons, including lack of awareness of vaccine-preventable diseases and uncertainty or misconceptions about the safety and efficacy of vaccination by parents and healthcare providers. The presence of these nonresponders/undervaccinated individuals represents a major health and economic burden to society, which will become particularly difficult to address in settings with limited public resources. This review describes innovative and experimental approaches that can help identify specific genomic profiles defining nonresponder individuals for whom specific interventions might be needed. We will provide examples that show how such information can be useful to identify novel biomarkers of safety and immunogenicity for future vaccine trials. Finally, we will discuss how system biology “OMICs” data can be used to design bioinformatic tools to predict the vaccination outcome providing genetic and molecular “signatures” of protective immune response. This strategy may soon enable identification of signatures highly predictive of vaccine safety, immunogenicity, and efficacy/protection thereby informing personalized vaccine interventions in vulnerable populations.

Despite relevant recommendations and evidences on the efficacy of influenza vaccination in health care workers (HCWs), vaccination coverage rates in Europe and Italy currently do not exceed 25%. Aim of the study is to measure the variations in vaccination coverage rates in an Italian pediatric hospital after a promotion campaign performed in the period October–December 2017. The design is a pre-post intervention study. The intervention is based on a wide communication campaign and an expanded offer of easy vaccination on site. The study was carried out at Bambino Gesù Children’s hospital in Rome, Italy, on the whole population of HCWs. Univariate and multivariate statistical analyses were performed. Vaccination coverage rate increased in 2017/18 campaign compared with the 2016/17 one (+95 HCWs vaccinated; +4.4%). The highest increases were detected in males (+45.7%), youngest employees (+142.9%), mean age of employment (+175%), other HCWs (+209.1%), Emergency Area (+151.6%) and Imaging Diagnostic Department (+200.0%). At multivariate logistic regression, working in some departments and being nurses represents a higher risk of being unvaccinated. Although the vaccination coverage rate remained low, a continuous increase of the coverage rate and development of a different consciousness in HCWs was highlighted. The study significantly identified the target for future campaigns.

Maternal immunization is a key strategy for protecting pregnant individuals and newborns from infectious diseases. This review examines the mechanisms and benefits of maternal immunization, with a focus on transplacental IgG transfer and immune system interactions. We provide an overview of current recommendations and the safety and efficacy profiles of maternal vaccines, including influenza, tetanus–diphtheria–acellular pertussis (Tdap), respiratory syncytial virus (RSV), COVID-19, and hepatitis B. Additionally, we analyze the barriers to maternal immunization, such as misinformation, vaccine hesitancy, and disparities in healthcare access, while exploring potential strategies to overcome these challenges through targeted educational initiatives, improved provider communication, and policy-driven interventions aimed at increasing vaccine confidence and accessibility. Finally, this review highlights recent innovations and future directions in maternal immunization, including emerging vaccines for Group B Streptococcus and cytomegalovirus. Expanding immunization programs and advancing research on maternal–fetal immunity are essential to optimizing vaccination strategies, improving public health outcomes, and reducing the global burden of infectious diseases.