Despite decades of research, HIV-1 continues to infect millions annually, underscoring the urgent need for a safe and effective vaccine to curb the ongoing global pandemic. Among the many strategies explored, viral vectors have been the most intensively studied, with adenoviral and poxviral platforms serving as the leading approaches. These vectors have advanced through extensive preclinical evaluation and multiple large-scale clinical trials, demonstrating safety and the ability to induce cellular and humoral responses. Yet, they have also revealed key challenges, including pre-existing vector immunity, limited durability of responses, and in some cases, increased susceptibility to infection. Importantly, these trials clarified the limitations of Env-focused immunity, highlighted the value of heterologous prime-boost regimens, and reinforced the dual need for broadly neutralizing antibodies and functional T cell responses. While vector-based COVID vaccines achieved protective efficacy, lessons learned from adenoviral and poxviral efforts continue to shape the field, directly informing the design of next-generation platforms such as mRNA and engineered viral vectors.
Publications by Year: 2025
2025
Childhood malnutrition in Syria has become an underrecognized threat to the country's recovery. Recent data indicate high rates of anemia and stunting among children under five years, especially in rural areas, reversing global progress and undermining both physical and cognitive development. These deficits carry long-term economic consequences, including reduced productivity and persistent intergenerational poverty. The crisis is preventable. Syria once maintained a national food-fortification program, and similar efforts in neighboring countries have demonstrated effectiveness even under economic strain. Reintroducing fortified bread, still the country's main staple, would offer a low-cost, high-impact intervention capable of improving child health on a large scale and restoring public confidence. Addressing malnutrition is therefore not only a public-health priority but also a critical step toward national recovery and the future stability of Syria's next generation.
BACKGROUND: This study presents patient-reported outcomes (PROs) from the phase 1/2 BRUIN (NCT03740529) trial of pirtobrutinib monotherapy for the treatment of B-cell malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL).
METHODS: PROs were collected at each cycle using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and item library (IL) sets for CLL/SLL- and MCL-related symptoms and an Expanded Fatigue measure. Prespecified analyses included descriptive change from baseline, time to worsening (TTW) using Kaplan-Meier method, and longitudinal analyses using a mixed model for repeated measures.
RESULTS: A total of 263 patients with CLL/SLL and 124 with non-blastoid MCL who received pirtobrutinib monotherapy after prior BTKi were included in the final PRO analysis. The proportion of patients with CLL/SLL who improved or remained stable from baseline through Cycle 31 remained above 80% for physical function (PF), CLL/SLL-related symptoms, fatigue, and global health status/quality of life (GHS/QoL). The proportion of patients with MCL who improved or remained stable through Cycle 20 remained above 70% for PF, MCL-related symptoms, fatigue, and GHS/QoL. Median TTW was not reached in either CLL or MCL. Longitudinal analyses for PF, CLL/SLL-related symptoms, fatigue, and GHS/QoL consistently met statistically significant and clinically-meaningful improvement from baseline for CLL. PRO assessments remained stable over time for MCL.
CONCLUSIONS: The final analysis from the BRUIN trial demonstrates stability in PROs throughout the duration of treatment with pirtobrutinib. Most patients with CLL/SLL and MCL reported stable or improved outcomes throughout the study.
This mini review article focuses on pharmacomicrobiomics, or the study of how the composition and activity of microorganisms in the body, in particular in the gut, impact drug pharmacokinetics and pharmacodynamics. This evolving field has profound implications for personalized medicine in the management of chronic inflammatory diseases. Particularly in dermatology, patient response to an expanding collection of biologic and small molecule inhibitor therapies coming out on the market remains unpredictable. The decision to start which therapy depends on physician preference, rather than based on what is expected to be the treatment response of each individual. This therapeutic uncertainty leads to sequential treatment failures, increased patient morbidity, and substantial healthcare expenditure. This mini-review synthesizes the evidence surrounding the gut microbiome as a predictive biomarker for therapeutic response in inflammatory skin diseases. We will examine the past use of pharmacomicrobiomics in oncology, where gut microbial signatures were found to predict response to immunotherapy in melanoma. We then analyze the present, focusing on the robust translational models from inflammatory bowel disease (IBD) and rheumatoid arthritis (RA), and the established gut dysbiosis in dermatologic conditions such as psoriasis and hidradenitis suppurativa (HS). Finally, we consider the future, discussing the potential for microbiome-based diagnostics to guide therapy selection for chronic inflammatory skin diseases.
There is increasing interest in smartphone digital mental health interventions (DMHIs) for managing schizophrenia. Currently, numerous applications (or, apps) that target different specific domains (e.g., medication adherence, social functioning, relapse prediction, and general mental well-being) have been developed and evaluated in research studies; however, few are commercially available to patients. The emergence of DMHIs has also highlighted the critical role of app engagement and the therapeutic alliance in effective treatments. This has driven the adoption of hybrid care models that integrate traditional psychotherapy with smartphone-based tools for symptom monitoring and intervention delivery, such as psychoeducation, cognitive-behavioral therapy for psychosis modules, and other targeted supports. This clinical review examines the current landscape of DMHIs for managing schizophrenia, including research evaluating outcomes related to effectiveness and implementation.
[This corrects the article DOI: 10.3389/fnins.2025.1516746.].
Early B cells develop centrally and then migrate peripherally to mediate the essential immune functions of antigen presentation, immune regulation, and immunoglobulin production. B cell development is tightly regulated, ensuring the generation of distinctive B cell clones, each carrying a fixed B cell receptor and therefore antigen specificity. Defects in B cell development can underlie a variety of clinical phenotypes, including immunodeficiency, autoimmunity, and B cell leukemia. The study of human genetic variation has enabled the discovery of critical pathways for immune cell development, differentiation, and generation of immune repertoire diversity. Here, we focus on the complete allelic spectrum impacting central B cell development, including rare and common genetic variation, to shed light on unique and shared mechanisms underlying predisposition to B cell lymphopenia, autoimmunity, and leukemia.
INTRODUCTION: Understanding how inflammatory dietary potential modulates the gut microbiota diversity, composition, and function remains a topic of ongoing debate. The present study aims to assess the longitudinal relationship between inflammatory dietary potential and gut microbiota characteristics in older adults with overweight/obesity and metabolic syndrome.
METHODS: This longitudinal sub-study and secondary analyses nested under the context of the PREvención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial included 648 participants (mean age 65 ± 5 years, 47 % women). Inflammatory dietary potential was based on energy-adjusted dietary inflammatory index (E-DII) score, assessed using a validated 143-item food frequency questionnaire. Gut microbiota was characterized using 16S rRNA sequencing and 518 identified faecal metabolites were analysed through liquid chromatography-tandem mass spectrometry. The relationship between E-DII score (exposure) and gut microbiota alpha and beta diversity and composition, in terms of microbial genera, and faecal metabolites (outcome) with available data at two timepoints (baseline and 1-year thereafter), and longitudinally, was subsequently analysed.
RESULTS: Anti-inflammatory dietary potential as measured by lower E-DII score, either as continuous or categorical, demonstrated significant associations with increased alpha diversity indices (i.e., Chao1, Inverse Simpson and Shannon; all P < 0.05), and distinct beta diversity profiles at baseline (R2 = 0.004; PERMANOVA P = 0.047) and after 1-year (R2 = 0.006; PERMANOVA P = 0.003). Furthermore, anti-inflammatory E-DII score was associated with 24 microbial genera, 4 faecal metabolites, and 1 metabolomic network (all FDR < 0.05). Pro-inflammatory E-DII score was also associated with 1 microbial genera and 2 faecal metabolites (all FDR < 0.05). Results remained significant when evaluating changes in E-DII over time with changes in alpha diversity indices and metabolomic network.
CONCLUSION: Anti-inflammatory dietary potential of diet may enhance gut microbiota diversity and potentially modulate its composition in older adults with metabolic syndrome.