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PubMed2026

Artificial intelligence for translational personalized neoantigen cancer vaccine development.

Personalized neoantigen cancer vaccine is a promising strategy for precision immunotherapy by targeting patient-specific and mutation-derived tumor antigens. Early clinical studies have demonstrated the feasibility, safety, and immunogenicity of these vaccines across multiple solid tumors, with encouraging outcomes particularly when combined with immune checkpoint blockade. However, broader clinical translation remains limited by sequential bottlenecks across the vaccine development pipeline, including false-positive neoantigen selection,  imperfect modeling of antigen processing and HLA presentation, limited prediction of T-cell receptor recognition, and challenges in formulation, delivery, and manufacturing. Artificial intelligence and advanced computational workflows are increasingly integrated into this pipeline to improve candidate prioritization and support more reproducible decision-making. In this review, we summarize clinical progress and key translational barriers in personalized neoantigen vaccination, and discuss how AI-enabled approaches may contribute across four major stages: multi-omics integration for neoantigen discovery, processing-aware HLA presentation prediction, structure-aware and TCR-informed immunogenicity modeling, and data-driven formulation optimization, particularly for lipid nanoparticle-based delivery systems. These approaches are able to help narrow biological and chemical search spaces, improve prioritization, and provide mechanistic insights into antigen presentation and immune recognition rather than replacing experimental validation. This articlefurther addresses future implementation challenges, including dataset diversity, model interpretability, prospective benchmarking, manufacturing traceability, and evolving regulatory frameworks for individualized mRNA cancer immunotherapies. Integrating computational innovation with rigorous immunological validation, scalable manufacturing, and regulatory oversight will be essential for advancing personalized neoantigen vaccines toward broader clinical implementation.

Cancer Vaccines↗

PubMed2025

Advancing the fight against tuberculosis: integrating innovation and public health in diagnosis, treatment, vaccine development, and implementation science.

Tuberculosis (TB) remains one of the leading causes of infectious disease mortality worldwide, increasingly complicated by the emergence of drug-resistant strains and limitations in existing diagnostic and therapeutic strategies. Despite decades of global efforts, the disease continues to impose a significant burden, particularly in low- and middle-income countries (LMICs) where health system weaknesses hinder progress. This comprehensive review explores recent advancements in TB diagnostics, antimicrobial resistance (AMR surveillance), treatment strategies, and vaccine development. It critically evaluates cutting-edge technologies including CRISPR-based diagnostics, whole-genome sequencing, and digital adherence tools, alongside therapeutic innovations such as shorter multidrug-resistant TB regimens and host-directed therapies. Special emphasis is placed on the translational gap-highlighting barriers to real-world implementation such as cost, infrastructure, and policy fragmentation. While innovations like the Xpert MTB/RIF Ultra, BPaLM regimen, and next-generation vaccines such as M72/AS01E represent pivotal progress, their deployment remains uneven. Implementation science, cost-effectiveness analyses, and health equity considerations are vital to scaling up these tools. Moreover, the expansion of the TB vaccine pipeline and integration of AI in diagnostics signal a transformative period in TB control. Eliminating TB demands more than biomedical breakthroughs-it requires a unified strategy that aligns innovation with access, equity, and sustainability. By bridging science with implementation, and integrating diagnostics, treatment, and prevention within robust health systems, the global community can accelerate the path toward ending TB.

diagnostic innovation↗

PubMed2015

New approaches to HIV vaccine development.

Development of a safe and effective vaccine for HIV is a major global priority. However, to date, efforts to design an HIV vaccine with methods used for development of other successful viral vaccines have not succeeded due to HIV diversity, HIV integration into the host genome, and ability of HIV to consistently evade anti-viral immune responses. Recent success in isolation of potent broadly neutralizing antibodies (bnAbs), in discovery of mechanisms of bnAb induction, and in discovery of atypical mechanisms of CD8T cell killing of HIV-infected cells, have opened new avenues for strategies for HIV vaccine design.

AIDS Vaccines↗

PubMed2026

Immunoinformatics Approach for Optimization of Targeted Vaccine Design: New Paradigm in Clinical Trials and Healthcare Management.

INTRODUCTION: The immunoinformatics approach combines bioinformatics and computational tools, offering a revolutionary method for improving vaccine development by analyzing immune responses at the molecular level. Immunoinformatics enables the creation of customized vaccines designed for specific infections or cancer cells. OBJECTIVE: The primary objective of immunoinformatics is to enhance the vaccine development process by predicting and boosting the body's immune response. It aims to identify potential immunogenic epitopes and biomarkers that are important for creating vaccines with greater specificity and efficacy, especially when dealing with large-scale data. METHODS: Immunoinformatics utilizes a combination of proteomic, genomic, and epigenomic data, as well as machine learning algorithms and artificial intelligence techniques. These tools predict how various immunological components, e.g., T-cell and B-cell epitopes, interact with the immune system. This approach allows researchers to avoid traditional trial-and-error methods, enabling the efficient identification of potential vaccine candidates. Additionally, personalized vaccines can be developed by considering individual genetic and immunological characteristics. RESULTS: The use of immunoinformatics techniques accelerates the screening of vaccine candidates, enhances patient stratification, and optimizes formulations for clinical trials. This approach has been shown to improve vaccine safety, efficacy, and development speed. It also holds promise for managing healthcare on a large scale by producing vaccines tailored to specific populations, thereby improving the overall effectiveness of vaccination programs. CONCLUSION: Immunoinformatics represents a transformative approach to vaccine research, improving clinical trial efficiency and enabling the development of more reliable, flexible, and personalized vaccines. This approach has the potential to significantly enhance global healthcare outcomes by accelerating the vaccine development process and optimizing vaccination strategies.

Immunoinformatics↗

PubMed2025

Bacteriophages as vaccine platforms: Opportunities and challenges in translation.

Bacteriophages (phages) have recently received increased interest as versatile candidates for vaccine development. Their inherent characteristics, such as ease of genetic manipulation, high-density antigen display, intrinsic immunostimulatory properties, demonstrated human safety, and scalability in bacterial hosts, make them attractive as next-generation vaccine platforms. Additionally, their cost-effective production, stability, and existing regulatory approval for food and compassionate phage therapy provide a strong foundation for further development of phage-based vaccines. This commentary summarizes the types of phages, the strategies used, and current advances in phage-based vaccine development for viral and bacterial targets, and discusses the promises and challenges of this platform for novel vaccine development. Phage-based vaccines represent an innovative and promising platform for vaccine development to address significant medical and public health challenges, particularly in antimicrobial resistance, pandemic preparedness, and One Health. Accumulative experimental data have demonstrated that phage-based vaccines induce specific cellular, humoral, and mucosal immune responses at magnitudes comparable to those induced by other vaccine platforms. However, a better understanding of phage biology (interactions with the human immune system and microbiome), more carefully designed preclinical studies, Good Manufacturing Practice production development, the regulatory framework, and ultimately clinical trials are needed before the full potential of this platform is realized.

Animals↗

PubMed2026

A reusable model of pangenome selection informs optimal surveillance strategies over vaccine introductions.

BACKGROUND: The human pathogen Streptococcus pneumoniae is a major cause of disease, including pneumonia and meningitis. The introduction of Pneumococcal Conjugate Vaccines (PCVs) initially reduced the burden of disease through a reduction of colonisation by vaccine-targeted serotypes. However, since PCVs only target a proportion of pneumococcal serotypes, they shift intraspecific competition, eventually allowing non-targeted types to 'replace' vaccine types. Understanding the host and pathogen factors causing replacement is important for future vaccine development. Mechanistic understanding of vaccine replacement dynamics is crucial for forecasting and optimisation of genomic surveillance strategies to evaluate realised vaccine effectiveness. METHODS: We developed a mathematical model of the genomic and demographic factors which explain vaccine replacement, used this model to replicate serotype-frequency changes, and investigated cost-effective genomic surveillance strategies. We extended a forward-time model based on the Wright-Fisher model, developing a user-friendly model framework that describes the post-vaccine dynamics of S. pneumoniae populations. Our model describes vaccine replacement as a function of vaccine impact, immigration of new strains, and negative frequency-dependent selection (NFDS) on the accessory genome content. RESULTS: We used our model to study vaccine replacement in newly sequenced genomic surveillance data from Kathmandu (Nepal), and existing data from Massachusetts (US) and Southampton (UK), with distinct surveillance strategies. We showed that the model with NFDS better replicates replacement dynamics than a null model without NFDS, and that NFDS likely only acts on part of the S. pneumoniae accessory genome. We found consistent estimates for vaccination effectiveness across the different study locations and region-specific genes under NFDS, highlighting the importance of conducting genomic surveillance in each country of interest. By simulating data from the model, we showed that an optimal surveillance strategy prioritises per-sampling sample size over sampling frequency for small sampling budgets. CONCLUSIONS: Our model can be used to predict vaccine replacement dynamics after PCV introduction, and can be easily reapplied to analyse new data from vaccine introductions or new regions. Our model is available in the R package Stubentiger (Studying Balancing Evolution (NFDS) To Investigate Genome Replacement) on GitHub https://github.com/bacpop/Stubentiger .

Streptococcus pneumoniae↗

PubMed2025

Global biological sample collections from tuberculosis studies: a scoping review.

Progress in tuberculosis vaccine development is hindered by the incomplete understanding of protective immunity and other disease mechanisms. An interconnected network of sample biorepositories from tuberculosis studies could help to address these gaps. To assess the feasibility of such a resource, we conducted a scoping review of tuberculosis observational studies and vaccine clinical trials. The included studies collected at least one biological sample from tuberculosis cases, contacts, or controls and had more than 100 participants. We contacted the corresponding authors of these studies to determine the sample availability and interest in interconnected biorepositories. For the period 2014-24, we identified 104 observational studies and 18 vaccine trials that collected biological samples from 35 075 tuberculosis cases, 39 450 contacts or controls, and 45 628 trial participants across 43 countries. The commonly collected samples were blood, human genomic DNA, RNA, and sputum. Interest among the contacted investigators was high. Interconnected sample biorepositories could facilitate large-scale investigations and accelerate progress towards tuberculosis vaccine development.

Humans↗

PubMed2025

Malaria: Factors affecting disease severity, immune evasion mechanisms, and reversal of immune inhibition to enhance vaccine efficacy.

Malaria is a complex parasitic disease caused by species of Plasmodium parasites. Infection with the parasites can lead to a spectrum of symptoms and disease severity, influenced by various parasite, host, and environmental factors. There have been some successes in developing vaccines against the disease recently, but the vaccine efficacies require improvement. Some issues associated with the difficulties in developing a sterile vaccine include high antigenic diversity, switching expression of the immune targets, and inhibition of immune pathways. Current vaccine research focuses on identifying conserved and protective epitopes, developing multivalent vaccines (including the whole parasite), and using more powerful adjuvants. However, overcoming the systematic immune inhibition and immune cell dysfunction/exhaustion may be required before high titers of protective antibodies can be achieved. Increased expression of surface molecules such as CD86 and MHC II on antigen-presenting cells and blocking immune checkpoint pathways (interactions of PD-1 and PD-L1; CTLA-4 and CD80) using small molecules could be a promising approach for enhancing vaccine efficacy. This assay reviews the factors affecting the disease severity, the genetics of host-parasite interaction, immune evasion mechanisms, and approaches potentially to improve host immune response for vaccine development.

Humans↗

PubMed2026

CRISPR-Cas and Infectious Diseases: A Decade of Translational Advances in Molecular Biotechnology.

CRISPR-Cas systems have emerged as a versatile tool for diagnosing, treating, and preventing infectious diseases. This review highlights translational advancements in CRISPR-Cas-based applications, concentrating on the past decades in diagnostics, therapeutic genome editing, and vaccine development. The article highlights key platforms like DETECTR and SHERLOCK, which enable rapid, sensitive pathogen detection, and explores CRISPR-Cas9 systems in therapeutic strategies for directly targeting viral genomes and combating antimicrobial resistance. It also examines the role of CRISPR-Cas9 in engineering live-attenuated and personalized neoantigen vaccines. Principal findings demonstrate a clear progression from experimental proof-of-concept to preclinical applications primarily in CRISPR-based diagnostics and the engineering of live-attenuated vaccine candidates, whereas translation in CRISPR-based therapeutics and personalized neoantigen vaccines for infectious diseases remains at earlier, more exploratory stages. CRISPR-based diagnostics have progressed further toward clinical evaluation than therapeutics due to delivery and safety constraints, while personalized neoantigen vaccines are included mainly as an emerging, comparative concept for infectious diseases rather than a mature application. This review uniquely integrates CRISPR-based diagnostics, therapeutics, and vaccine development within a single infectious disease framework, critically assesses their current maturity, and systematically highlights technical, regulatory, and ethical barriers alongside realistic future priorities. The review concludes that while CRISPR-Cas holds transformative potential for infectious disease management, significant challenges in delivery efficiency, off-target effects, and ethical regulation must be addressed to ensure safe and equitable clinical translation.

Humans↗

PubMed2024

In vitro one-pot construction of influenza viral genomes for virus particle synthesis based on reverse genetics system.

The reverse genetics system, which allows the generation of influenza viruses from plasmids encoding viral genome, is a powerful tool for basic research on viral infection mechanisms and application research such as vaccine development. However, conventional plasmid construction using Escherichia coli (E.coli) cloning is time-consuming and has difficulties handling DNA encoding genes toxic for E.coli or highly repeated sequences. These limitations hamper rapid virus synthesis. In this study, we establish a very rapid in vitro one-pot plasmid construction (IVOC) based virus synthesis. This method dramatically reduced the time for genome plasmid construction, which was used for virus synthesis, from several days or more to about 8 hours. Moreover, infectious viruses could be synthesized with a similar yield to the conventional E.coli cloning-based method with high accuracy. The applicability of this method was also demonstrated by the generation of recombinant viruses carrying reporter genes from the IVOC products. This method enables the pathogenicity analysis and vaccine development using genetically modified viruses, and it is expected to allow for faster analysis of newly emerging variants than ever before. Furthermore, its application to other RNA viruses is also expected.

Genome, Viral↗

PubMed2026

Construction of Reverse Genetics System for Feline Calicivirus FCV-BJ616 and Proteomic Analysis.

Feline calicivirus (FCV) is a primary cause of upper respiratory tract infections and oral ulcerative disease in cats and exhibits substantial genetic diversity that complicates prevention and control. In this study, we isolated the FCV-BJ616 strain, established a reverse-genetics system, and investigated its pathogenic mechanisms, thereby providing a foundation for antibody-based therapies and broad-spectrum vaccine development. The virus was purified by three rounds of plaque cloning, and its morphology was examined by electron microscopy. VP1 expression was confirmed by immunofluorescence and Western blotting. Using integrated systems-biology and reverse-genetics approaches, an infectious clone of rFCV-BJ616 was successfully assembled and rescued, exhibiting genetic stability comparable to that of the parental strain. In vivo infection experiments showed that rFCV-BJ616 retained wild-type virulence, causing persistent high fever, weight loss, and multiorgan pathology in infected cats. Proteomic analysis indicated that infection with FCV-BJ616 or rFCV-BJ616 markedly activated cytokine-mediated inflammatory signaling pathways. Both FCV-BJ616 and rFCV-BJ616 significantly upregulated the expression of IL-8, S100A8/A9, and TLR3, which are associated with acute inflammation and tissue damage. Furthermore, elevated IFN-β levels concomitant with STAT1 downregulation suggested a transient attenuation of antiviral signaling during early immune activation. These findings were corroborated by ELISA-based validation of serum cytokine profiles. Collectively, this study provides new insights into the molecular pathogenesis and evolution of FCV-BJ616 and establishes a robust reverse-genetics platform for precise genome manipulation and future vaccine development.

Animals↗

PubMed2026

A genetic manipulation tool based on the GP35 recombinase for targeted gene editing in mycoplasmas of ruminants.

Pathogenic ruminant mycoplasmas are major etiological agents in cattle and small ruminants and are responsible for substantial economic losses in the livestock industry. Progress in pathogenesis research and vaccine development has been hampered by a lack of effective genetic tools. The applicability of common genome editing platforms, such as CRISPR, is inherently restricted in these organisms owing to their minimal genomes, the absence of a cell wall, and low homologous recombination efficiency. Although transposon-mediated random mutagenesis and single-base editing are currently used in the editing of bovine mycoplasma, the stochastic nature of transposons, the risk of single-base random deamination, and limitations in editing window selection hinder the genetic manipulation of bovine mycoplasma. Here, we introduce a plasmid-based methodology that employs the GP35 recombinase from bacteriophage SPP1 to mediate long single-stranded DNA (ssDNA) recombineering, thereby enabling precise gene insertions and deletions in Mycoplasma bovis, with a positive-editing rate of 77.78% - 100%. This targeted system eliminates the risk of random deamination. Leveraging this tool, we generated a panel of M. bovis mutants affecting metabolic and virulence genes and obtained key insights into Mb0564, identified as a novel adhesin. The 192 to 287 aa region of GP35 is critical for interaction with SSB. Structural conservation analysis further suggested that this GP35-ssDNA editing system possesses a high potential for translation to other ruminant pathogens. Collectively, our approach expands the existing genetic toolkit for M. bovis, advances synthetic biology and M. bovis pathobiology, facilitates vaccine development, and strengthens the control of high-impact livestock diseases in line with the One Health framework.

Animals↗

PubMed2026

Influence of Major Histocompatibility Complex (MHC) Diversity on Immune Modulation, Pathogenesis, and Control of Lumpy Skin Disease Virus.

INTRODUCTION: Lumpy Skin Disease Virus (LSDV), a member of the genus Capripoxvirus within the family Poxviridae, is an economically important transboundary viral pathogen affecting cattle and water buffalo. The disease causes severe production losses through decreased milk yield, infertility, hide damage, reduced growth performance, and occasional mortality. The rapid geographic spread of LSDV, together with its vectorborne transmission and emerging recombinant strains, has intensified the need for improved understanding of viral pathogenesis, host immune responses, and effective prevention strategies. In particular, the role of the bovine Major Histocompatibility Complex (BoLA/MHC) in regulating antiviral immunity, disease susceptibility, and vaccine responsiveness has gained increasing scientific attention. METHODS: This review summarises the published literature related to the epidemiology, transmission, structure, pathogenesis, diagnosis, prevention, and control of LSDV, with special emphasis on the immunological and molecular role of bovine MHC molecules. Relevant studies concerning BoLA-mediated antigen presentation, immunoinformaticsbased epitope prediction, vaccine development, antiviral drug repurposing, molecular docking, genomic surveillance, and diagnostic approaches, including PCR- and ELISAbased assays, were critically evaluated. Recent advances in computational biology, molecular virology, and host-pathogen interaction studies were also reviewed. RESULTS: The reviewed studies demonstrate that Lumpy Skin Disease Virus (LSDV) possesses a complex double-stranded DNA genome enabling immune modulation and efficient transmission through arthropod vectors such as mosquitoes, ticks, and biting flies. Disease progression involves systemic viral replication, vascular injury, dermal necrosis, and inflammatory skin lesions. Real-time PCR remains the most sensitive diagnostic method for early detection, while ELISA supports surveillance. Evidence highlights the central role of bovine Major Histocompatibility Complex (BoLA) molecules in antigen presentation and T-cell activation. Computational studies identified promising BoLA-binding epitopes and repurposed antiviral candidates, including ivermectin, theaflavin, canagliflozin, and tepotinib, for future therapeutic development. DISCUSSION: Current evidence indicates that effective LSDV control requires integration of molecular diagnostics, vector management, vaccination, and host immunogenetics. BoLAguided immunoinformatics provides promising opportunities for developing multi-epitope vaccines, although experimental validation remains essential. Similarly, repurposed antiviral candidates require comprehensive in vivo and pharmacological evaluation before clinical application. Future research should focus on elucidating viral immune-evasion mechanisms, validating predicted epitopes, and translating computational findings into practical vaccines and therapeutics for sustainable disease control. CONCLUSION: Lumpy Skin Disease continues to pose a major threat to global cattle health and livestock economies. Advances in molecular diagnostics, genomic surveillance, antiviral drug discovery, and BoLA-guided vaccine design provide promising opportunities for improved disease control. Understanding the interaction between LSDV and the bovine MHC system is essential for developing next-generation vaccines, immunotherapeutics, and precision disease-management strategies. Future research should prioritise experimental validation of predicted epitopes, large-scale vaccine trials, and mechanistic studies on host-virus immune interactions to establish effective and sustainable global control programs for LSDV.

BoLA↗

PubMed2026

Global vaccine readiness: equity-by-design in pandemic preparedness and response.

INTRODUCTION: COVID-19 showed that rapid vaccine development and roll-out, while lifesaving, can still yield large, avoidable harms when equity is not considered from the outset. Disparities in vaccine timing and coverage, especially in low-resource settings, amplified health and economic burdens, highlighting the need for preparedness frameworks that combine speed with fairness. AREAS COVERED: We synthesize evidence from literature and policy reports regarding global vaccine roll-out, focusing on avertable mortality under alternative sharing scenarios, procurement design, pooled mechanisms such as COVAX, and the role of distributed manufacturing and delivery capacity. We also examine how transparent data-sharing, effective public communication, genomic surveillance, adaptive trial designs, and modeling hubs can support more responsive and equitable vaccine deployment. Across six reflection points, we translate these lessons into practical priorities for future pandemic readiness, including strengthening healthcare infrastructure, equitable procurement, data transparency, and safeguarding public health decision-making from political and commercial distortion. EXPERT OPINION: We argue that equity-by-design is essential if vaccine innovation is to deliver equitable public health impact. This requires geographically distributed manufacturing, transparency, equity-conditioned advance purchase agreements, and pre-agreed, epidemiology-triggered allocation of vaccines. We recommend institutionalizing disaggregated reporting, standardized data-sharing, greater pathogen genomic sequencing capacity, and communication strategies that support public health protection while countering misinformation.

Humans↗

PubMed2026

Comprehensive genomic and computational insights into Brucella suis: pan-genome analysis, evolutionary perspectives, and in-silico vaccine design.

BACKGROUND: Brucella suis is a zoonotic intracellular pathogen responsible for brucellosis, mainly in swine and humans. Although numerous genome sequences are publicly available, an integrative genomic analysis combining pan-genome architecture, structural organization, evolutionary relationships, and vaccine-associated targets remains limited. RESULTS: In this study, we analyzed 91 publicly available B.suis genomes to characterize their pan-genome composition and genomic structure. The pan-genome exhibited an open configuration, indicating continued genomic diversification. A total of 2,146 core genes were identified, representing conserved functions essential for species maintenance, while the accessory genome reflected strain-level variability. Phylogenetic reconstruction based on single-copy orthologs revealed distinct evolutionary clades among the strains. A complementary phylogenetic analysis of pan-genome gene presence-absence patterns further supported clade differentiation and highlighted variation in accessory gene repertoires. Comparative synteny and genome structural analyses demonstrated largely conserved chromosomal organization with localized rearrangements across strains. Screening of the core proteome identified 64 putative antigenic proteins with predicted surface localization and immunogenic properties. Additionally, resistance-associated determinants related to tetracycline and doxycycline were detected in one genome within the dataset. CONCLUSIONS: This comprehensive genomic analysis defines the pan-genome structure, evolutionary relationships, and genome organization of B.suis. The integration of core and pan-genome-based phylogenies provides complementary insights into strain diversification, while the identified conserved antigenic candidates offer a foundation for future experimental validation and rational vaccine development strategies.

Genome, Bacterial↗

PubMed2016

Immunodominant Dengue Virus-Specific CD8+ T Cell Responses Are Associated with a Memory PD-1+ Phenotype.

UNLABELLED: Dengue disease is a large public health problem that mainly afflicts tropical and subtropical regions. Understanding of the correlates of protection against dengue virus (DENV) is poor and hinders the development of a successful human vaccine. The present study aims to define DENV-specific CD8(+)T cell responses in general and those of HLA alleles associated with dominant responses in particular. In human blood donors in Nicaragua, we observed a striking dominance of HLA B-restricted responses in general and of the allele B*35:01 in particular. Comparing these patterns to those in the general population of Sri Lanka, we found a strong correlation between restriction of the HLA allele and the breadth and magnitude of CD8(+)T cell responses, suggesting that HLA genes profoundly influence the nature of responses. The majority of gamma interferon (IFN-γ) responses were associated with effector memory phenotypes, which were also detected in non-B*35:01-expressing T cells. However, only the B*35:01 DENV-specific T cells were associated with marked expression of the programmed death 1 protein (PD-1). These cells did not coexpress other inhibitory receptors and were able to proliferate in response to DENV-specific stimulation. Thus, the expression of particular HLA class I alleles is a defining characteristic influencing the magnitude and breadth of CD8 responses, and a distinct, highly differentiated phenotype is specifically associated with dominant CD8(+)T cells. These results are of relevance for both vaccine design and the identification of robust correlates of protection in natural immunity. IMPORTANCE: Dengue is an increasingly significant public health problem as its mosquito vectors spread over greater areas; no vaccines against the virus have yet been approved. An important step toward vaccine development is defining protective immune responses; toward that end, we here characterize the phenotype of the immunodominant T cell responses. These DENV-reactive T cells express high levels of the receptor programmed death 1 protein (PD-1), while those from disease-susceptible alleles do not. Not only does this represent a possible correlate of immunodominance, but it raises the hypothesis that PD-1 might be a regulator that prevents excessive damage while preserving antiviral function. Further, as this study employs distinct populations (Nicaraguan and Sri Lankan donors), we also confirmed that this pattern holds despite geographic and ethnic differences. This finding indicates that HLA type is the major determinant in shaping T cell responses.

Alleles↗

PubMed2026

Research note: Development of a recombinant duck enteritis virus vector expressing DHAV-3 VP1 and DTMUV prM/TE genes.

Duck enteritis virus (DEV) is a promising viral vector for vaccine development. In a previous study, an HDR-CRISPR/Cas9-based strategy was used to generate a recombinant virus, rDEV-DHAV-VP1, by inserting the VP1 gene of duck hepatitis A virus type 3 (DHAV-3) into the UL27/UL26 intergenic region of DEV vaccine strain, resulting in good genetic stability and immunogenicity. In the present study, the same strategy was applied to insert the EGFP gene into the US7/US8 and LORF11/UL55 intergenic regions of a DEV vaccine strain. Among the evaluated insertion sites, the highest level of EGFP expression was observed at the US7/US8 locus, followed by the UL27/UL26 locus. Based on rDEV-DHAV-VP1, the pre-membrane (prM) and truncated envelope (TE) genes of duck Tembusu virus (DTMUV) were further inserted into the US7/US8 locus, resulting in a bivalent recombinant virus, rDEV-VP1-prM/TE. The recombinant virus exhibited growth kinetics comparable to those of the parental virus, while maintaining efficient expression and high genetic stability of the inserted genes. These findings indicate that the HDR-CRISPR/Cas9 system is an efficient strategy for generating stable DEV-based recombinant vectors and provides a promising platform for the development of multivalent vaccines against major duck viral diseases.

CRISPR/Cas9 genome editing↗

PubMed2025

Advances in Helicobacter pylori lipopolysaccharide structure and function.

Helicobacter pylori is a widespread pathogen responsible for chronic gastritis, peptic ulcers, and an elevated risk of gastric cancer. Lipopolysaccharide (LPS), localized exclusively in the outer leaflet of the outer membrane, is essential for maintaining bacterial integrity. Recent advances have deepened our understanding of H. pylori LPS structure, particularly lipid A modifications and the redefinition of the core oligosaccharide and O-antigen regions. The complete set of enzymes involved in LPS biosynthesis has been identified in the reference strain G27, and comparative genomics has revealed a notable regional difference (the absence of the heptan domain in East Asian strains). Here, we summarize recent insights into the structure and function of H. pylori LPS, emphasizing its role in bacterial persistence and its promise as a target for LPS-based glycoconjugate vaccine development.

Helicobacter pylori↗