Abstract
MR1T cells are a novel population of T cells that recognize self-metabolite antigens presented by the monomorphic molecule MR1. MR1T cells can kill tumor cells, showing promise for off-the-shelf anti-tumor immunotherapy.

We demonstrate that human MR1T cell clones exhibit potent cytotoxicity against leukemic cell lines and primary leukemias. In vivo studies revealed that a prototype MR1T cell clone reduced tumor burden and enhanced survival in a xenotransplant HEL AML mouse model. By exploiting pharmacological modulation of tumor metabolism with the cytostatic antimetabolite Pemetrexed, we observed increased MR1 surface expression, which led to a significant boost in MR1-mediated killing by MR1T cells.

Our findings provide proof of concept that drug treatment may enhance MR1T cell killing of tumor cells in vivo, supporting the development of combination strategies to maximize the therapeutic efficacy of this T cell population.

Abstract

Lumpy skin disease virus (LSDV) is increasingly recognized as a promising recombinant vector for multivalent vaccine development due to its strong immunogenicity and safety profile in cattle. Bluetongue virus (BTV), in contrast, is characterized by high genetic variability and complex pathogenesis, creating challenges for vaccine design. An associated vaccine targeting both pathogens would represent a valuable tool for integrated disease control.

This project focuses on the rational selection and incorporation of bluetongue virus genes VP2, VP7, and NS1, identified as key protective antigens, into the recombinant platform based on LSDV proteins. VP2 and VP7 are the major capsid proteins responsible for serotype-specific neutralizing antibody responses and induction of protective immunity, while NS1 contributes to robust cellular immune activation. Through comprehensive analysis of scientific and patent literature, these genes were prioritized as the most promising candidates for broad-spectrum and durable protection.

The design strategy involves fusing BTV antigens with LSDV immunogenic proteins to ensure stable expression and presentation within the recombinant construct. This integrated system is expected to elicit a combined humoral and cellular immune response, enhancing protection against both LSDV and BTV, while minimizing the risk of adverse post-vaccination effects.

By uniting evidence-based antigen selection with recombinant vector engineering, this work outlines a pathway toward an innovative, associated vaccine capable of addressing two economically important cattle diseases simultaneously, thus advancing the field of veterinary vaccinology and livestock biosecurity.

This study is carried out with the financial support of the Committee of Science of the Ministry of Science and Higher Education of the Republic of Kazakhstan, AP26198397.

Abstract

Aging is accompanied by a diminished immune capacity to defend against infections and a chronic, low-grade inflammatory state known as immunosenescence, which promotes autoantibody production. In addition to its impact on infection susceptibility, aging is also recognized as an environmental risk factor for various autoimmune diseases. Among them, systemic lupus erythematosus (SLE)—a prototypic autoimmune disease characterized by diverse autoantibody production and systemic inflammation—shows an association with aging. However, the mechanisms by which aging contributes to its pathogenesis remain unclear. Our laboratory identified a novel CD4⁺ T cell subset linked to aging and autoimmunity, including SLE, using flow cytometry and RNA sequencing of over 400 healthy individuals and patients with autoimmune diseases. We designated this subset as “ThA (Age-associated helper T) cells” (Science Immunology, 2024). ThA cells are CXCR3^midCD4⁺ T cells with a unique chemokine receptor profile distinct from other Th subsets and are regulated by the transcription factor ZEB2. They exhibit cytotoxic activity and B cell helper function while being CXCR5-negative, suggesting a central role in extrafollicular humoral immune responses that are closely associated with autoantibody production. Intriguingly, integrated analysis of gene expression data from various CD4⁺ T cell subsets and clinical information in SLE patients revealed that the gene expression changes in ThA cells most strongly reflect SLE disease activity. In this session, I will present recent findings on ThA cells, which increase with aging and contribute to the pathogenesis of autoimmune diseases, along with future perspectives.

Abstract:  
The development of innovative vaccine technologies has been a turning point in preventive and therapeutic medicine. Unlike traditional vaccines based on attenuated or inactivated pathogens, new platforms are designed to address more complex health challenges, including persistent infections, malignancies, and immune-mediated disorders. These approaches have been driven by the need to improve safety, minimize adverse reactions, and expand vaccination coverage beyond acute infectious diseases. One of the most significant catalysts for this rapid transformation has been the emergence of global health emergencies, particularly the COVID-19 pandemic. The unprecedented urgency of this crisis has accelerated the transition of third-generation vaccines, such as messenger RNA, DNA, and viral vector platforms, from experimental concepts to large-scale human applications. Their rapid design, adaptability, and synthetic manufacturing processes have enabled rapid responses to evolving viral threats, demonstrating the potential of these technologies to reshape future vaccination strategies.

Despite these advances, significant challenges remain. Issues such as the durability of immune protection, susceptibility to antigenic variation, cold chain requirements, and equitable global access continue to limit widespread implementation. Moreover, the novelty of these platforms raises questions about long-term safety, regulatory compliance, and public acceptance. Addressing these barriers will require coordinated scientific innovation, adaptable clinical research frameworks, and international collaboration to ensure the benefits of next-generation vaccines are realized globally. Ultimately, the integration of these technologies into sustainable health systems presents an opportunity not only to strengthen pandemic preparedness but also to expand the role of vaccines in combating chronic and emerging diseases.