Search Results (1,332)

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies, with 5-year survival rates consistently below 5% despite advances in surgery, chemotherapy, and targeted therapy. Worldwide, PDAC remains highly lethal, with 458,918 new cases and 432,242 deaths in 2018—about a 94% mortality-to-incidence ratio. The limited therapeutic efficacy is largely attributed to the pronounced heterogeneity of the disease, late clinical presentation, and the strongly immunosuppressive tumor microenvironment. In recent years, mRNA-based vaccines encoding patient-specific neoantigens have emerged as a promising immunotherapeutic modality. By delivering tailored antigenic sequences, these vaccines are capable of eliciting potent cytotoxic T-cell responses against tumor-restricted epitopes, thereby enhancing tumor immunogenicity while minimizing off-target effects. This review summarizes the biological rationale underlying mRNA vaccination in PDAC, recent progress in preclinical and early clinical trials, and key obstacles related to antigen selection, delivery platforms, and the immunosuppressive stroma. The potential integration of neoantigen mRNA vaccines into multimodal therapeutic strategies, including immune checkpoint inhibition and chemotherapy, is also discussed, underscoring their prospective role in overcoming resistance mechanisms and improving clinical outcomes in PDAC. However, most current data come from early-phase trials, with long-term benefits yet unproven. Definitive conclusions on efficacy and survival await results from ongoing randomized studies expected by 2028–2029. Further progress in neoantigen identification, delivery systems, and combination strategies is crucial to fully harness mRNA vaccine potential in PDAC. Full article

Duck viral hepatitis (DVH), a highly contagious disease, is caused primarily by duck hepatitis A virus (DHAV). The viral genotypes exhibit significant diversity, creating a challenge as monovalent vaccines fail to provide cross-genotype protection in ducklings. This study aimed to design a multi-epitope peptide vaccine targeting different genotypes of DHAV. Using immunoinformatics approaches, we systematically identified key antigenic determinants, including linear B-cell epitopes, cytotoxic T-cell epitopes (CTL), and helper T-cell epitopes (HTL). Based on these, a novel vaccine candidate was developed. The vaccine construct was subjected to rigorous computational validation: (1) Molecular docking with Toll-like receptors (TLRs) predicted immune interaction potential. (2) Molecular dynamics simulations assessed complex stability. (3) In silico cloning ensured prokaryotic expression feasibility. Then, we conducted preliminary experimental validation for the actual effect of the vaccine candidate, including recombinant protein expression in E. coli, enzyme-linked immunosorbent assay (ELISA) quantification of humoral responses, and Western blot analysis of cross-reactivity. ELISA results demonstrated that the vaccine candidate could induce high-titer antibodies in immunized animals, with potency reaching up to 1:128,000, and the immune serum showed strong reactivity with recombinant VP proteins. Western blot analysis using duck sera confirmed epitope conservancy across genotypes. Collectively, the multi-epitope vaccine candidate developed in this study represents a highly promising broad-spectrum strategy against DHAV. The robust humoral immunity it elicits, coupled with its demonstrated cross-reactivity, constitutes compelling proof-of-concept, laying a solid foundation for advancing to subsequent challenge trials and translational applications. Full article

Background/Objectives: Epitope-based matching has emerged as a refined approach for assessing donor–recipient compatibility in renal transplantation. However, limited data are available on HLA Class I epitope distribution among Indian patients, particularly from northern India, where substantial allelic diversity is known to influence immunological risk. Methods: This retrospective analysis evaluated HLA Class I single-antigen bead (SAB) antibody data from 218 consecutive renal-transplant candidates who tested positive for anti-HLA antibodies between July 2018 and September 2024. HLA Class I epitopes were identified and analyzed using MATCH IT Antibody Software (Immucor, version 1.5.0). Demographic variables and sensitization history (previous transplant, transfusion, pregnancy) were reviewed. Results: A total of 504 distinct epitopes were identified, with 65GK and 163LG emerging as the most frequent motifs. The predominance of these epitopes mirrors the high prevalence of alleles such as HLA-A*24 and HLA-B*35 reported in North-Indian populations. The data suggest a strong influence of regional allele architecture on the immunogenic epitope landscape. Conclusions: This study provides the first baseline characterization of HLA Class I epitope distribution among northern-Indian renal-transplant candidates. The findings emphasize the need for establishing population-specific HLA epitope databases and highlight the potential of epitope-based matching to enhance donor selection and minimize immunological risk in Indian transplantation programs. Full article

Bovine parainfluenza virus type 3 (BPIV3) is a significant pathogen implicated in bovine respiratory disease complex (BRDC), leading to lung tissue destruction, immunosuppression, and subsequent bacterial infections in cattle, hence incurring considerable economic losses globally. Notwithstanding its importance, a limited number of commercial vaccinations are presently accessible. The fusion (F) protein and hemagglutinin-neuraminidase (HN) protein, as protective antigens of the Paramyxoviridae family, can elicit neutralizing antibodies and are regarded as optimal candidates for the creation of genetically modified vaccines. A multi-epitope-based peptide vaccine (MEBPV) was developed by immunoinformatics methodologies by choosing epitopes from the F and HN proteins characterized by high antigenicity, moderate toxicity, and limited allergenic potential. The epitopes were combined with suitable linkers and adjuvants to produce the vaccine, whose physicochemical qualities, immunological attributes, solubility, and structural stability were improved and evaluated using computational methods. Molecular docking and molecular dynamics simulations demonstrated the strong potential binding affinity and stability of the vaccination with TLR2, TLR3, and especially TLR4 receptors. Immune simulations forecasted strong humoral and cellular responses, accompanied by a significant elevation in interferon-γ (IFN-γ) production. The vaccine sequence was later cloned into the pET-28a (+) vector for possible expression in Escherichia coli. Despite in silico predictions suggesting a favorable immunogenic potential, additional in vitro and in vivo studies are necessary to confirm its protective efficacy and safety. This research establishes a solid foundation for the creation of safe and efficacious subunit vaccines targeting BPIV3 and presents novel perspectives for the formulation of vaccinations against additional viral infections. Full article

Background/Objectives: T cell bispecific antibodies (TCBs) result in the activation of T cell receptor signaling upon binding to tumor antigens providing signal 1 to T cells. To enhance and sustain their activity, a co-stimulatory signal 2 is required. Here CEACAM5-targeted 4-1BBL antibody fusion proteins for combination with CEA-TCB (cibisatamab, RG7802) are described in an investigation of the relationship between the CEACAM5 epitope and T cell activity. Methods: CEACAM5-targeted bispecific 4-1BBL antibody fusion proteins (CEA-4-1BBLs) were generated based on different CEACAM5 antibodies and characterized in vitro in Jurkat-4-1BB reporter and PBMC cell assays. The impact of shed CEA on in vitro activity and cynomolgus cross-reactivity was studied. In vivo efficacy was assessed in human stem cell humanized NSG mice xenograft models bearing MKN-45 and HPAFII tumors. Results: MFE23-4-1BBL and Sm9b-4-1BBL showed superior functional activity in Jurkat-4-1BB reporter and primary T cell assays when combined with the CD3 antibody V9, whereas T84.66-LCHA-4-1BBL and A5B7-4-1BBL performed better when combined with CEA-TCB. In humanized NSG mice MKN-45 and HPAFII xenograft models, T84.66-LCHA-4-1BBL mediated the best anti-tumor efficacy. Conclusions: For the assessment of the combination of CEA-TCB with CEA-4-1BBL, co-stimulatory antibody fusion protein in vitro assays are not sufficient to fully capture the complex relationships affecting efficacy. Thus, screening with different cell assays and in vivo efficacy studies in combination with CEA-TCB are essential to select the best candidate. Based on the totality of data on the T84.66-LCHA-4-1BBL antibody fusion protein comprising the CEACAM5 antibody, T84.66-LCHA was selected as the optimal combination partner for CEA-TCB. Full article

Background: Poxviruses constitute a family of large dsDNA viruses that can infect a plethora of species including humans. Historically, poxviruses have caused a health burden in multiple outbreaks. The large genome of poxviruses favors reverse vaccinology approaches that can determine potential antigens and epitopes. Here, we propose the modeling of a user-friendly database containing the predicted antigens and epitopes of a large cohort of poxvirus proteomes using the existing PoxiPred method for reverse vaccinology of poxviruses. Methods: In the present study, we obtained the whole proteomes of as many as 37 distinct poxviruses. We utilized each proteome to predict both antigenic proteins and T-cell epitopes of poxviruses with the aid of an Artificial Intelligence method, namely the PoxiPred method. Results: In total, we predicted 3966 proteins as potential antigen targets. Of note, we considered that this protein may exist in a set of proteoforms. Subsets of these proteins constituted a comprehensive repository of 54,291 linear T-cell epitopes. We combined the outcome of the predictions in the format of a web tool that delivers a database of antigens and epitopes of poxviruses. We also developed a comprehensive repository dedicated to providing access to end-users to obtain AI-based screened antigens and T-cell epitopes of poxviruses in a user-friendly manner. These antigens and epitopes can be utilized to design experiments for the development of effective vaccines against a plethora of poxviruses. Conclusions: The TCEPVDB repository, already deployed to the web under an open-source coding philosophy, is free to use, does not require any login, does not store any information from its users. Full article

Background and Aims: C1q is an autoantigen in different autoimmune disorders, Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN) among them. The two functional domains of C1q, the collagen-like region (CLR) and the globular head region (gC1q), are frequently recognized by autoantibodies in SLE and LN when C1q is immobilized. We studied whether autoantibodies to C1q in SLE and LN patients recognized C1q as a soluble autoantigen and whether the act of immobilization was a prerequisite for the recognition of C1q autoepitopes localized on gC1q domains. Methods: The interaction of soluble C1q and its globular fragments ghA, ghB, and ghC with immobilized IgG autoantibodies (and vice versa) from sera of 48 patients with SLE and LN was studied with ELISA. Data were compared using Spearman correlation coefficient. Fluorescence spectroscopy was used to study the interaction between C1q and LN IgG autoantibodies both presented in solution. Results: We found that anti-C1q autoantibodies from SLE and LN patients specifically bound C1q and gC1q fragments, ghA, ghB, and ghC, both as immobilized and soluble antigens. Correlation analysis indicated a negative correlation between the levels of autoantibodies against immobilized and soluble C1q and immobilized and soluble gC1q fragments which indicates different epitopes when these proteins were recognized as autoantigens in soluble and immobilized conformations. Conclusions: Serum C1q in patients with SLE is a target molecule for binding from anti-C1q autoantibodies. The gC1q region undergoes a conformational change in an immobilized and a soluble form, thus exposing different epitope-binding sites. Full article

Background: Respiratory syncytial virus (RSV) is a major pathogen of acute lower respiratory tract infection (LRTI) in infants, the elderly, and immunocompromised individuals. This review focuses on the progress of RSV vaccine development, especially subunit vaccines targeting the fusion protein (F) and attachment glycoprotein (G), aiming to summarize key strategies, challenges, and future directions in the field. Methods: The review is based on a comprehensive literature search and analysis of recent studies on RSV vaccine development, with a specific focus on subunit vaccines and related technologies. Results: Approved vaccines such as Abrysvo and Arexvy utilize structural engineering to stabilize the prefusion conformation of the F protein (PreF), thereby exposing neutralizing epitopes. Subunit vaccine candidates such as DS-Cav1 and DT-PreF enhance stability through disulfide bonds and dityrosine linkages, while ADV110 targets the conserved domain of the G protein to elicit cross-strain immunity. Virus-like particle (VLP) vaccines like IVX-A12 combine RSV and human metapneumovirus antigens to provide broad-spectrum immunity. However, challenges exist, including maintaining PreF stability, overcoming immunosenescence in the elderly, and addressing safety concerns like Guillain-Barré syndrome (GBS). Conclusions: Future RSV vaccine development should center on combined PreF-G protein vaccines, VLP technology, and optimizing cold-chain logistics to improve global accessibility and overcome existing challenges, thereby providing more effective prevention and control of RSV infections. Full article

Background: Molecular mimicry contributes to the development of unwanted responses to self-antigens. Autoimmune phenomena have been observed in diseases caused by Aedes aegypti-transmitted arboviruses, but the occurrence of mimicry between salivary and human proteins has been unexplored. Methods: We used bioinformatic tools to determine if peptides from Aedes aegypti salivary proteins were present in the human proteome. We further characterized the potential of shared sequences to induce immunity by analyzing their predicted binding to MHC molecules and their occurrence in peptides from the Immune Epitope Database (IEDB). Results: We analyzed 9513 octapeptides from 29 Aedes aegypti salivary proteins against the human proteome and found 47 peptides identical to sequences from 52 human proteins, ranging in length from 8 to 18 amino acids. We found 302 matches of peptides predicted to bind with high affinity to MHC-I and MHC-II alleles associated with autoimmune diseases, and 14 human peptides containing shared sequences with Aedes aegypti salivary proteins validated as immunogenic in the IEDB. Conclusions: These results support the existence of molecular mimicry between Aedes aegypti salivary proteins and human antigens and provide a framework for studies to determine its contribution to responses directed to self-antigens in the context of arboviral infections. Full article

Background/Objectives: Streptococcus suis is a zoonotic pathogen that causes infections in pigs and humans, leading to significant economic losses. S. suis can evade the immune system of hosts and induce persistent infections. Early detection and vaccination are crucial for controlling the disease in swine industries. This study aimed to investigate candidate recombinant protein for antibodies against S. suis detection and subunit vaccine development. Methods: The whole genome of S. suis BM407 was analyzed using bioinformatic tools to predict suitable proteins and genes for recombinant protein expression. Partial extracellular factor protein (epf) genes of S. suis serotype 2 DMST18783 were amplified. A 3301 bp amplicon was digested, and a specific 615 bp fragment was inserted into a pQE81L-KAN vector. Then, the constructed plasmid was cloned and expressed in Escherichia coli DH10β. Purified protein was analyzed using SDS-PAGE. In addition, translated amino acid sequences were analyzed for immune response properties, molecular docking, molecular dynamic simulation, and epitope prediction. Results: The amino acid sequence of recombinant extracellular factor protein (rEF) was revealed as a promising antigen containing putative protective regions as linear epitopes. Furthermore, the rEF was expressed as a histidine-tagged recombinant protein, and its properties were nearly similar to the predicted rEF using bioinformatic tools. Binding of the recombinant EF (rEF) protein was found to reduce fluctuations in the swine toll-like receptor 2. Furthermore, the rEF contained several regions that were predicted to be epitopes for both B-cells and T-cells. Conclusions: This study indicates that the recombinant EF fragment is a promising candidate for detecting antibodies against S. suis and as a component of a subunit vaccine. Full article

Senecavirus A (SVA) causes a vesicular disease in pigs with clinical signs indistinguishable from those of other swine vesicular diseases. To enable serological differentiation infected from vaccinated animals (DIVA), we developed indirect ELISAs (iELISAs) based on recombinant non-structural proteins (NSPs). A His-tagged tandem antigen, r3AB-3C, was designed by integrating immunodominant B-cell epitopes from 3AB and 3C proteins, and was successfully expressed in Escherichia coli (E. coli) and purified alongside the individual r3AB and r3C proteins. Serological evaluation results showed that the immunoreactivity of the r3AB-3C iELISA was superior to that of r3AB, which in turn was better than r3C. The r3AB-3C and r3AB iELISAs were subsequently validated. The cut-off values were established at sample-to-positive (S/P) ratios of ≥0.2635 for the r3AB-3C iELISA and ≥0.5775 for the r3AB iELISA. The r3AB-3C iELISA demonstrated higher sensitivity for detecting infection-induced antibodies than the r3AB iELISA, despite the later seroconversion of anti-NSP antibodies compared to neutralizing antibodies. In a serosurvey, the r3AB-3C iELISA revealed seropositivity rates of 35.2% in 2023 and 22.3% in 2024. In conclusion, the r3AB-3C iELISA is a valuable serological tool for monitoring SVA infection, effectively supporting DIVA strategies. Full article

Dengue virus remains a major global health threat due to the lack of a safe and broadly effective vaccine. Traditional antibody-based vaccines often show limited protection and can exacerbate disease severity in individuals without prior exposure. A new generation of T-cell epitope-based vaccines offers a promising and safer approach by activating the cellular arm of the immune system to complement antibody responses. Instead of targeting only surface structural proteins, these vaccines focus on highly conserved peptide regions within non-structural proteins, particularly NS3 and NS5, that are shared across all four dengue virus serotypes. Peptides such as DTTPFGQQR, KPGTSGSPI, and MYFHRRDLRL have been identified as potent immunogenic targets capable of inducing strong cytotoxic and helper T-cell responses, promoting viral clearance and long-term immune memory. Advanced immunoinformatic enables precise prediction and selection of epitopes with high binding affinity to human leukocyte antigens and broad cross-serotype conservation. These peptides can be integrated into next-generation vaccine delivery systems, including messenger RNA and nanoparticle platforms, which enhance antigen presentation, improve molecular stability, and reduce the risk of antibody-dependent disease enhancement. Together, this integrative design represents a rational path toward a safer, cross-protective, and durable dengue vaccine that closely mimics the balanced cellular and humoral immunity observed after natural infection, offering renewed hope for effective global dengue prevention. Full article

Background/Objectives: Varicellovirus bovinealpha1 and Varicellovirus bovinealpha5 (BoAHV-1 and BoAHV-5), respectively, are widely distributed pathogens that cause distinct clinical conditions in cattle including infectious bovine rhinotracheitis, infectious pustular vulvovaginitis/balanoposthitis, and meningoencephalitis. Due to the establishment of viral latency, controlling these infections is challenging, and vaccination remains the most effective strategy. In this study, vaccine candidates targeting both BoAHV-1 and BoAHV-5 were developed. Methods: A synthetic gene encoding immunodominant epitopes from the gB and gD proteins and tegument phosphoprotein of BoAHV-1 and BoAHV-5 was designed to produce a multi-epitope recombinant antigen, expressed both in a prokaryotic system (RecBoAHV) and by a modified vaccinia Ankara (MVA-BoAHV) viral vector. The binding affinity of MHC-I to bovine leukocyte antigens (BoLA) was predicted using the NetMHCpan tool (version 4.1). The immunogenicity of the vaccine candidates was evaluated in rabbit and mouse models, using prime-boost immunization protocols. Sera from bovines naturally infected with BoAHV-1 and/or BoAHV-5 were used to evaluate the chimeric protein antigenicity. Immune responses were assessed by indirect ELISA and Western blot. Results: The recombinant multi-epitope protein was effectively recognized by IgG and IgM antibodies in sera from cattle naturally infected with BoAHV-1 or BoAHV-5, confirming the antigenic specificity. Both RecBoAHV and MVA-RecBoAHV induced strong and specific humoral immune responses in rabbits following a homologous prime-boost regimen. In mice, both homologous and heterologous prime-boost protocols revealed robust immunogenicity, particularly after the second booster dose. Conclusions: These findings highlight the immunogenic potential of the RecBoAHV multi-epitope vaccine candidates for controlling BoAHV-1 and BoAHV-5 infections. Further characterization of these vaccine formulations is currently underway in bovine, the target specie. Full article

Cancer immunotherapy has redefined oncology’s goals, aiming for durable systemic immunity rather than mere cytoreduction. However, many solid tumors remain refractory due to immunosuppressive microenvironments and antigenic heterogeneity. Local tumor ablation techniques—including radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, irreversible electroporation (IRE), and high-intensity focused ultrasound (HIFU)—are being re-evaluated beyond their historic cytoreductive role. This comprehensive review synthesizes the paradigm of tumor ablation as an in situ vaccination strategy, a concept that leverages the tumor itself as a source of antigens and the ablation process to generate endogenous adjuvants. We detail the mechanistic underpinnings, highlighting how ablation induces immunogenic cell death (ICD), releasing damage-associated molecular patterns (DAMPs) such as calreticulin, ATP, HMGB1, and cytosolic DNA. These signals activate innate immunity via pathways like cGAS-STING, promote dendritic cell maturation, and facilitate epitope spreading. We critically examine the determinants of efficacy, including the critical impact of ablation modality on the “DAMP signature,” the necessity of complete ablation, and the pivotal role of the host’s immune contexture. Furthermore, we explore the induction of tertiary lymphoid structures (TLS) as a key anatomical site for sustained immune priming. Translational strategies are extensively discussed, focusing on optimizing procedural techniques, rationally combining ablation with immune checkpoint inhibitors (ICIs) and innate immune agonists, and developing a robust biomarker framework. By adopting the core principles of vaccinology—meticulous attention to antigen, adjuvant, route, and schedule—ablation can be engineered into a reproducible platform for systemic immunotherapy. This review concludes by addressing current limitations and outlining a roadmap for clinical translation, positioning interventional oncology as a central discipline in the future of immuno-oncology. Full article

Background: Mammalian orthoreovirus is a ubiquitous double-stranded RNA virus that causes mild respiratory and enteric infections, primarily in infants and young children. Its significant environmental stability and association with conditions like celiac disease highlight an unmet medical need, as no licensed vaccine or antiviral treatment currently exist. Methods: An immunoinformatics-driven approach was employed to design a multi-epitope vaccine. The highly antigenic inner capsid protein Sigma-2 was used to predict cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and linear B cell epitopes using NetCTL, NetMHCpan, NetMHCIIpan, and IEDB tools. Selected epitopes were fused with appropriate linkers. The construct’s antigenicity, allergenicity, and physicochemical properties were evaluated. The tertiary structure was predicted with AlphaFold2, refined, and validated. Molecular docking with TLR2 and TLR4 was performed using HDOCK, and immune response simulation was conducted with C-ImmSim. Finally, the sequence was codon-optimized for E. coli expression using JCat. Results: The final vaccine construct comprises one CTL, four HTLs, and one B cell epitope. It is antigenic (VaxiJen score: 0.5026), non-allergenic, and non-toxic and possesses favorable physicochemical properties, including stability (instability index: 32.28). Molecular docking revealed exceptionally strong binding to key immune receptors, particularly TLR2 (docking score: −324.37 kcal/mol). Immune simulations predicted robust antibody production (elevated IgM, IgG1, and IgG2) and lasting memory cell formation. Codon optimization yielded an ideal CAI value of 0.952 and a GC content of 57.15%, confirming high potential for recombinant expression. Conclusions: This study presents a novel multi-epitope vaccine candidate against reovirus, designed to elicit broad cellular and humoral immunity. Comprehensive in silico analyses confirm its structural stability, potent interaction with innate immune receptors, and high potential for expression. These findings provide a strong rationale for further wet-lab studies to validate its efficacy and advance it as a promising prophylactic candidate. Full article