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Keywords = systems vaccinology

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32 pages, 7579 KB  
Review
Nanoparticle Engineering in Modern Vaccinology: From Delivery Platforms to Immune-Programming Architectures
by Andrey Bogoyavlenskiy, Vladimir Berezin, Madina Alexyuk, Pavel Alexyuk and Elmira Omirtayeva
Molecules 2026, 31(14), 2501; https://doi.org/10.3390/molecules31142501 - 17 Jul 2026
Viewed by 327
Abstract
Recent advances in vaccinology have accelerated the shift from conventional live-attenuated and inactivated vaccines toward subunit and nucleic acid-based platforms. Although these next-generation vaccines offer improved safety, rapid adaptability, and manufacturing flexibility, their relatively low intrinsic immunogenicity often requires efficient adjuvants and delivery [...] Read more.
Recent advances in vaccinology have accelerated the shift from conventional live-attenuated and inactivated vaccines toward subunit and nucleic acid-based platforms. Although these next-generation vaccines offer improved safety, rapid adaptability, and manufacturing flexibility, their relatively low intrinsic immunogenicity often requires efficient adjuvants and delivery systems. Nanoparticle-based vaccine platforms have therefore emerged as versatile tools capable of protecting antigens, improving targeted delivery, and modulating both innate and adaptive immune responses. This review summarizes the major classes of nanovaccine platforms, including lipid and polymeric nanoparticles, self-assembling protein nanostructures such as virus-like particles and ferritin nanocages, saponin-based self-assembling complexes, and inorganic nanomaterials. Particular attention is given to how vaccine performance is determined not only by material composition but also by nanoparticle physicochemical properties, biodistribution, cellular uptake, and mechanisms of immune activation. We further discuss the major challenges limiting clinical translation, including scalable manufacturing, safety evaluation, quality control, regulatory requirements, and long-term biocompatibility. Finally, emerging strategies involving hybrid and personalized nanovaccine platforms are highlighted, illustrating how nanotechnology and immunoengineering are transforming vaccine development for both prophylactic and therapeutic applications. Full article
(This article belongs to the Special Issue Nanomaterials for Biomedicine: Innovations and Challenges)
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26 pages, 3418 KB  
Article
SARS-CoV-2 mRNA Vaccination Induces Reduced T-Cell Apoptosis in Patients with Solid Tumors
by Ana Belda-Marco, Lucía Serrano-García, Andrés Moret, Carlos Fresneda-Portillo, María Victoria Domínguez-Márquez, Ana Comes-Raga, Beatriz Jávega, José-Enrique O’Connor, Juan Carlos Andreu-Ballester, Antonio Llombart-Cussac and María Leonor Fernández-Murga
Int. J. Mol. Sci. 2026, 27(14), 6173; https://doi.org/10.3390/ijms27146173 - 10 Jul 2026
Viewed by 333
Abstract
Messenger RNA (mRNA) vaccines represent a transformative platform in vaccinology, with applications extending beyond SARS-CoV-2 to other infectious diseases and cancer immunotherapy. However, patients with solid tumors receiving active anticancer treatment were largely underrepresented in pivotal vaccination trials, limiting understanding of vaccine-induced immunity [...] Read more.
Messenger RNA (mRNA) vaccines represent a transformative platform in vaccinology, with applications extending beyond SARS-CoV-2 to other infectious diseases and cancer immunotherapy. However, patients with solid tumors receiving active anticancer treatment were largely underrepresented in pivotal vaccination trials, limiting understanding of vaccine-induced immunity in this population. In this prospective exploratory study, we assessed humoral and cellular immune responses after two doses of SARS-CoV-2 mRNA vaccines in 39 patients with solid tumors undergoing active treatment. Blood samples were collected before vaccination and approximately two months after the second vaccine dose, prior to the next treatment cycle. Anti-spike IgG, neutralizing antibodies, receptor-binding domain (RBD) levels, interleukin-6 (IL-6), hematological parameters, immune cell subsets, T-cell differentiation, and early apoptosis in αβ and γδ T-cell subsets were analyzed. Vaccination induced a robust humoral response, with high post-vaccination anti-spike IgG levels (median 988.69 BAU/mL), 97.44% seropositivity, 96.88% true seroconversion among baseline IgG−/NAb− patients, and strong neutralizing antibody activity (median 85.73%). Hematological parameters and IL-6 levels remained broadly stable, suggesting no detectable increase in systemic inflammation during the study period. Cellular analyses identified a reduction in peripheral CD19+ B-cell frequencies and decreased early apoptosis, particularly in CD8+ T cells and CD3+CD56+ NKT-like cells. Although changes in T-cell frequencies and differentiation profiles were also observed, these findings were attenuated after exclusion of participants with possible prior SARS-CoV-2 exposure and should be interpreted as exploratory. Overall, these results show that patients with solid tumors receiving active treatment can mount robust humoral responses to SARS-CoV-2 mRNA vaccination and suggest measurable post-vaccination changes in lymphocyte dynamics, including reduced early T-cell apoptosis. Full article
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28 pages, 5617 KB  
Review
Avian Orthoreovirus in China: Molecular Evolution, Transmission Ecology, Immune Modulation, and Integrated Control in the Genomic Era
by Lijuan Yin, Peier Huang, Yanhua Xu, Ouyang Peng, Kensi Zhu, Ermin Xie, Shenghua Yang, Jin Liu, Xuesong Li, Zhuanqiang Yan, Jianping Qin and Wencheng Lin
Viruses 2026, 18(7), 728; https://doi.org/10.3390/v18070728 - 30 Jun 2026
Viewed by 393
Abstract
Avian orthoreovirus (ARV) has re-emerged as one of the most important viral pathogens affecting modern poultry production worldwide. In China, the epidemiological landscape of ARV has undergone a substantial transformation over the past decade, characterized by increasing genotypic diversity, frequent genome reassortment, an [...] Read more.
Avian orthoreovirus (ARV) has re-emerged as one of the most important viral pathogens affecting modern poultry production worldwide. In China, the epidemiological landscape of ARV has undergone a substantial transformation over the past decade, characterized by increasing genotypic diversity, frequent genome reassortment, an expanding host range, and recurrent vaccine-breakthrough outbreaks. Growing evidence indicates that contemporary ARV populations evolve within a dynamic multispecies transmission network shaped by intensive poultry production, host adaptation, and vaccine-associated selective pressures. Recent molecular studies have revealed extensive genetic heterogeneity among circulating strains and highlighted the limitations of conventional σC-based classification systems for accurately describing viral evolution, pathogenicity, and antigenic diversity. Whole-genome analyses further demonstrate that reassortment among chicken-origin, duck-origin, and goose-origin orthoreoviruses plays a pivotal role in generating novel viral variants with altered biological properties. In parallel, accumulating evidence suggests that ARV exerts broad immunomodulatory effects through the disruption of innate antiviral signaling, impairment of lymphoid organ function, interference with vaccine responsiveness, and the enhancement of susceptibility to secondary infections. These findings indicate that ARV should be regarded not only as an arthrotropic pathogen but also as an important immunopathological agent influencing flock health and productivity. This review summarizes current knowledge of ARV in China, with an emphasis on molecular epidemiology, genomic evolution, reassortment mechanisms, transmission ecology, immune interference, vaccine escape, and integrated prevention strategies. Particular attention is given to the increasing importance of whole-genome surveillance, phylodynamic analysis, and multispecies epidemiological monitoring for understanding contemporary ARV evolution. Future perspectives involving structural vaccinology, precision immunization, metagenomics-assisted surveillance, and predictive evolutionary modeling are also discussed. Collectively, sustainable ARV control will likely require genome-informed and adaptive prevention frameworks integrating virology, immunology, epidemiology, and precision poultry management. Full article
(This article belongs to the Special Issue Avian Reovirus 2026)
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27 pages, 7890 KB  
Review
Viral Vaccine Adjuvant Strategies for Shaping Durable Immunity Across the Human Lifespan
by Swarandeep Singh, Surabhi Gautam, Vidhi Thakkar, Sanjeev Kumar and Devyani Joshi
Vaccines 2026, 14(6), 508; https://doi.org/10.3390/vaccines14060508 - 4 Jun 2026
Viewed by 705
Abstract
Vaccination remains one of the most effective strategies for preventing infectious diseases. Yet, the success of modern vaccines increasingly depends on the rational design of adjuvants that enhance and shape immune responses. In this review, we examine current and emerging adjuvant strategies for [...] Read more.
Vaccination remains one of the most effective strategies for preventing infectious diseases. Yet, the success of modern vaccines increasingly depends on the rational design of adjuvants that enhance and shape immune responses. In this review, we examine current and emerging adjuvant strategies for viral vaccines across the human lifespan. Traditional adjuvants, particularly aluminum salts, have long served as the foundation of vaccine formulations. Still, their limitations have driven the exploration of novel platforms, including emulsions, nucleic acid-based adjuvants, and advanced particulate delivery platforms with intrinsic immunostimulatory properties. These newer approaches act through diverse mechanisms, such as activating innate immune pathways via pattern recognition receptors (PRRs) and stimulating antigen-presenting cells (APCs), thereby improving both humoral and cellular immunity. Recent advances in molecular biology, nanotechnology, and systems vaccinology have deepened mechanistic understanding and enabled more precise modulation of immune responses. However, significant challenges remain, including incomplete knowledge of adjuvant mechanisms, limited diversity among licensed adjuvants, safety concerns, and inconsistent efficacy across age groups. In particular, immune immaturity in infants and immunosenescence in older adults highlight the need for age-specific adjuvant strategies. The review identifies critical gaps in comparative studies, long-term safety data, and the development of adjuvants capable of inducing broad and durable immunity. Further, this article integrates licensed and emerging viral vaccine adjuvants through a lifespan framework. Addressing these limitations through interdisciplinary research and precision-based approaches will be essential for advancing next-generation vaccines and improving global preparedness for emerging infectious diseases. Full article
(This article belongs to the Special Issue Advances in Vaccine Adjuvants)
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19 pages, 681 KB  
Review
Cultures Through Time: Forging a Xeno-Free Future for Cell Culture-Based Virology
by Arvind Singh Kaulsay, Nurshariza Abdullah and Nur Amelia Azreen Adnan
Vaccines 2026, 14(6), 476; https://doi.org/10.3390/vaccines14060476 - 28 May 2026
Viewed by 539
Abstract
As a cornerstone of modern science, cell lines are the foundational platforms for key medical advances. They enable vaccinology (through viral propagation and attenuation), gene therapy (via vector development), and biopharmaceutical production (via recombinant protein expression). Designer mammalian, avian, and insect expression systems, [...] Read more.
As a cornerstone of modern science, cell lines are the foundational platforms for key medical advances. They enable vaccinology (through viral propagation and attenuation), gene therapy (via vector development), and biopharmaceutical production (via recombinant protein expression). Designer mammalian, avian, and insect expression systems, including Vero, MDCK, HEK293, BHK21, CHO, PER.C6, EB66, and Sf21/Sf9, have become indispensable cellular platforms, delivering enhanced biologic yields, superior genetic stability, and validated end-product biosafety. Simultaneous advances in cell culture media optimization have enabled a critical shift from serum-dependent media to serum-free, chemically defined, and xeno-free alternatives, which aim to restore compositional traceability of culture media components, reduce potential residual xenogeneic proteins in serum-supplemented media, and promote reproducibility even at the molecular level. This review emphasizes the far-reaching influence of cell culture systems as the expression powerhouse that sustains modern virology, whilst focusing on recent cell-engineering methods and optimization strategies in culture media that have facilitated this shift. Full article
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27 pages, 1632 KB  
Review
One Health Perspective on the Enterotoxigenic Escherichia coli Diversity
by Ricardo Rodríguez-Martínez, Jetsi Mancilla-Rojano, Sara A. Ochoa, Graciela Castro-Escarpulli, Ariadnna Cruz-Córdova and Juan Xicohtencatl-Cortes
Microorganisms 2026, 14(6), 1171; https://doi.org/10.3390/microorganisms14061171 - 22 May 2026
Viewed by 2833
Abstract
In this review, the virulence factors involved in enterotoxigenic Escherichia coli (ETEC) colonization and pathogenesis are analyzed, with an emphasis on colonization factors, enterotoxins and antigenic diversity as central challenges in vaccine development. ETEC remains a major cause of diarrhea worldwide, particularly in [...] Read more.
In this review, the virulence factors involved in enterotoxigenic Escherichia coli (ETEC) colonization and pathogenesis are analyzed, with an emphasis on colonization factors, enterotoxins and antigenic diversity as central challenges in vaccine development. ETEC remains a major cause of diarrhea worldwide, particularly in vulnerable populations. Despite extensive research, no broadly protective licensed vaccines are available largely because of antigenic heterogeneity and the limited understanding of immune correlates of protection. We identified critical knowledge gaps in antigen prioritization and host–pathogen interactions and translational limitations that have hindered vaccine success. We critically evaluated emerging platforms (including mRNA vaccines, nanoparticles, multiepitope strategies, and reverse vaccinology) for their potential to overcome variability and increase immunogenicity. We examined the roles of ecological environmental reservoirs associated with human and animal systems, in addition to antimicrobial pressure, in shaping ETEC evolution and vaccine effectiveness within a One Health framework; moreover, we propose an integrated approach that links genomic surveillance-based vaccine ecology and next-generation vaccine technologies to support adaptive immunogen design. This review provides actionable recommendations for the development of broadly protective and translationally viable ETEC vaccines from the One Health perspective. Full article
(This article belongs to the Special Issue Advancement in Enterotoxigenic Escherichia coli (ETEC) Vaccines)
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28 pages, 417 KB  
Review
A Comparative Review of Veterinary and Human Vaccine Development Strategies: Insights into Herpesvirus Vaccinology from Latency to Elimination
by Guangyi Liu, Xiaoyang Zhao, Yuezhi Lin, Xiaojun Wang and Diqiu Liu
Vaccines 2026, 14(3), 249; https://doi.org/10.3390/vaccines14030249 - 7 Mar 2026
Viewed by 1578
Abstract
Background: Members of the virus family Herpesviridae are among the most successful pathogen groups in evolutionary history. They not only pose a serious public health threat to humans but also cause significant economic losses in the global livestock industry. The primary immunological challenge [...] Read more.
Background: Members of the virus family Herpesviridae are among the most successful pathogen groups in evolutionary history. They not only pose a serious public health threat to humans but also cause significant economic losses in the global livestock industry. The primary immunological challenge in developing sterilizing vaccines is the lifelong latency of herpesviruses in the nervous system or lymphoid tissues. Methods: This analysis compares the vaccine strategies designed against the five most important Alphaherpesvirinae pathogens: HSV-1/2, PRV, BHV-1, EHV-1/4, and FHV-1. The contrast between the globally licensed veterinary vaccines and the relative stagnation in the field of human HSV vaccines is stark. However, there are notable success stories regarding the implementation of ‘Marker Vaccines’ (DIVA strategies) in veterinary medicine. This review examines various vaccine modalities, assessing their potential to mitigate clinical outbreaks and their shortcomings in preventing viral shedding and establishing latency. Results: This study reveals common technical bottlenecks across species, attributed to immune evasion mechanisms such as the downregulation of MHC I, TAP inhibition, the failure to induce robust mucosal IgA, and safety concerns regarding the recombination of live vectors. Conclusions: This review highlights several promising avenues that could lead to enhanced herpesvirus vaccines and recommends the rational design of T-cell epitopes alongside innovative mucosal adjuvants. Furthermore, it bridges the gap between veterinary and human vaccinology from a One Health perspective, suggesting that lessons learned from veterinary practices could facilitate necessary breakthroughs in human medicine. Full article
(This article belongs to the Special Issue Vaccine and Vaccination in Veterinary Medicine)
18 pages, 1089 KB  
Review
From Innate to Adaptive: Paradigm Shifts and Frontier Challenges in Next-Generation Vaccine Design
by Siqi Huang, Shaochen Yu, Mengjie Zhang, Yuting Huang, Beibei Tian and Jian Lu
Vaccines 2026, 14(3), 228; https://doi.org/10.3390/vaccines14030228 - 28 Feb 2026
Cited by 1 | Viewed by 2305
Abstract
The unprecedented success of mRNA vaccines during the COVID-19 pandemic marks a fundamental paradigm shift in vaccinology, moving the field from empirical pathogen modification toward the rational engineering of host immunity. This review synthesizes recent breakthroughs to construct a conceptual framework for understanding [...] Read more.
The unprecedented success of mRNA vaccines during the COVID-19 pandemic marks a fundamental paradigm shift in vaccinology, moving the field from empirical pathogen modification toward the rational engineering of host immunity. This review synthesizes recent breakthroughs to construct a conceptual framework for understanding how modern vaccines function as programmable immune instructions. We first analyze the innate immune system as an instructional center, where recognition of vaccine components dictates the quality of ensuing adaptive responses. We then examine the germinal center (GC) as a micro-evolutionary engine for antibody maturation, the output of which can be tuned by vaccine design. The discussion centers on three integrated pillars of next-generation vaccines: computationally designed immunogens, spatiotemporally controlled adjuvant systems, and intelligent delivery platforms, emphasizing that their synergy is essential for achieving broad, durable protection against complex pathogens. Finally, we explore how the convergence of systems vaccinology, artificial intelligence, and personalized medicine is guiding the field toward a more predictable and rapid-response future, while also outlining key advances and persistent challenges. Full article
(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)
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25 pages, 919 KB  
Review
From Design to Clinical Use: mRNA Vaccines for Infectious Diseases and Cancer
by Yulin Cui, Ziyue Liang and Hua Cong
Vaccines 2026, 14(3), 202; https://doi.org/10.3390/vaccines14030202 - 25 Feb 2026
Cited by 3 | Viewed by 3093
Abstract
mRNA vaccines represent a revolutionary advance in vaccinology, boasting advantages like rapid development, robust immunogenicity and flexible antigen design over traditional vaccines. This review systematically summarizes the core research progress of mRNA vaccines, including their structural composition with five functional elements and novel [...] Read more.
mRNA vaccines represent a revolutionary advance in vaccinology, boasting advantages like rapid development, robust immunogenicity and flexible antigen design over traditional vaccines. This review systematically summarizes the core research progress of mRNA vaccines, including their structural composition with five functional elements and novel subtypes (linear mRNA, self-amplifying RNA, circular RNA) with unique biological characteristics and application value. It elaborates on the immune activation mechanism of mRNA vaccines, which mimic natural viral infection to trigger both innate and adaptive immunity, and analyzes mainstream delivery systems (lipid nanoparticles, dendritic cells, protamine, exosomes, polymers) with their respective performance, advantages and bottlenecks. This review also details the clinical application status of mRNA vaccines in infectious diseases (influenza, rabies, monkeypox, SARS-CoV-2, HIV, parasites) and cancer therapy, highlighting promising preclinical and clinical results of candidate vaccines and combined therapeutic regimens. Additionally, it addresses the current limitations of mRNA vaccines, such as delivery inefficiency, production costs, and cold chain constraints. Finally, this review prospects the future development direction, emphasizing that the optimization of delivery systems, antigen design and production processes will further promote the clinical translation and diversified application of mRNA vaccines in disease prevention and treatment. Full article
(This article belongs to the Section Vaccine Design, Development, and Delivery)
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45 pages, 5401 KB  
Review
Virus Biomimetic-Delivery Systems for the Production of Vaccines
by Marcela-Elisabeta Barbinta-Patrascu, Irina Negut and Bogdan Bita
Biomimetics 2026, 11(2), 150; https://doi.org/10.3390/biomimetics11020150 - 18 Feb 2026
Cited by 1 | Viewed by 2248
Abstract
The persistent emergence of infectious diseases has underscored the critical demand for next-generation vaccine technologies that are safe, effective, and scalable. This review explores virus biomimetic delivery systems, focusing on virus-like particles (VLPs) and virosomes as promising platforms for vaccine and therapeutic development. [...] Read more.
The persistent emergence of infectious diseases has underscored the critical demand for next-generation vaccine technologies that are safe, effective, and scalable. This review explores virus biomimetic delivery systems, focusing on virus-like particles (VLPs) and virosomes as promising platforms for vaccine and therapeutic development. VLPs are self-assembled nanostructures composed of viral structural proteins that mimic native virions without carrying genetic material, while virosomes are reconstituted viral envelopes that retain functional glycoproteins but lack a nucleocapsid. Both systems provide strong immunogenicity and safety by mimicking viral architecture while eliminating the risk of replication. The paper examines various expression platforms for VLP production, including bacterial, yeast, insect, mammalian, and plant-based systems, highlighting their respective advantages, challenges, and optimization strategies. Mechanistic insights into antigen presentation, immune activation, and cellular uptake pathways are discussed to explain their superior performance in eliciting humoral and cellular immune responses. Furthermore, current applications of VLPs and virosomes in vaccines against major pathogens such as SARS-CoV-2, influenza, Newcastle disease virus, malaria, hepatitis, and respiratory syncytial virus are reviewed, demonstrating their versatility and clinical potential. By integrating molecular engineering, nanotechnology, and biofabrication strategies, virus biomimetic systems represent a transformative frontier in vaccinology, immunotherapy, and targeted drug delivery. Full article
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24 pages, 1480 KB  
Review
Future Perspectives on the Application of Systems Biology and Generative Artificial Intelligence in the Design of Immunogenic Peptides for Vaccines
by José M. Pérez de la Lastra, Isidro Sobrino, Víctor M. Rodríguez Borges and José de la Fuente
Vaccines 2026, 14(2), 177; https://doi.org/10.3390/vaccines14020177 - 13 Feb 2026
Cited by 1 | Viewed by 2058
Abstract
Peptide-based vaccines offer a modular and readily manufacturable platform for both prophylactic and therapeutic immunization. However, their broader translation has been constrained by the limited capacity to predict protective immunity directly from sequence-level features. Recent advances in systems vaccinology and high-throughput immune profiling [...] Read more.
Peptide-based vaccines offer a modular and readily manufacturable platform for both prophylactic and therapeutic immunization. However, their broader translation has been constrained by the limited capacity to predict protective immunity directly from sequence-level features. Recent advances in systems vaccinology and high-throughput immune profiling have substantially expanded the experimental evidence, while generative artificial intelligence now enables de novo design of peptide immunogens and multi-epitope antigens under precisely controlled constraints. This review approaches how these complementary developments are transforming peptide vaccine research, moving beyond classical reverse vaccinology and conventional epitope prediction toward integrated, data-driven design frameworks. We discuss key generative model architectures and conditioning strategies aligned with vaccine objectives, including approaches that account for structural presentation, antigen processing and population-level human leukocyte antigen (HLA) diversity. Central to this perspective is the requirement for rigorous experimental validation and for strengthening the computational–experimental feedback loop through iterative in vitro and in vivo testing informed by systems-level immune readouts. We highlight representative applications spanning infectious diseases, cancer immunotherapy and vector-borne vaccinology, and we outline major technical and translational challenges that must be addressed to enable robust real-world deployment. Finally, we propose future directions for precision peptide vaccinology, emphasizing standardized functional benchmarks, the development of richer curated datasets linking sequence space to immune outcomes, and the early incorporation of formulation and delivery constraints into generative design pipelines. Full article
(This article belongs to the Special Issue The Development of Peptide-Based Vaccines)
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16 pages, 737 KB  
Review
Metabolomics in Infectious Diseases and Vaccine Response: Insights into Neglected Tropical and Non-Neglected Pathogens
by Mahbuba Rahman, Hasbun Nahar Hera and Urbana Islam Barsha
Infect. Dis. Rep. 2026, 18(1), 10; https://doi.org/10.3390/idr18010010 - 12 Jan 2026
Cited by 1 | Viewed by 1439
Abstract
Background/objectives: Metabolomics has emerged as a powerful systems-biology tool for deciphering dynamic metabolic alterations occurring during infectious diseases and following vaccination. While genomics and proteomics provide extensive molecular and regulatory information, metabolomics uniquely reflects the biochemical phenotype associated with infection, immune activation, and [...] Read more.
Background/objectives: Metabolomics has emerged as a powerful systems-biology tool for deciphering dynamic metabolic alterations occurring during infectious diseases and following vaccination. While genomics and proteomics provide extensive molecular and regulatory information, metabolomics uniquely reflects the biochemical phenotype associated with infection, immune activation, and immunometabolic reprogramming. The objective of this review is to provide an integrated analysis of metabolomics applications across both neglected tropical diseases (NTDs) and non-NTD pathogens, highlighting its dual role in biomarker discovery and vaccine response evaluation. Methods: A comprehensive literature-based synthesis was conducted to examine metabolomic studies in infectious diseases and vaccinology. Metabolic perturbations associated with specific pathogens, as well as vaccine-induced metabolic changes and correlates of immune responses, were systematically analyzed and compared across NTD and non-NTD contexts. Results: Distinct pathogen- and vaccine-associated metabolic signatures were identified, reflecting alterations in glycolysis, amino acid metabolism, lipid remodeling, and immunoregulatory pathways. Comparative analysis revealed both shared and disease-specific metabolic biomarkers across NTDs and non-NTD infections. Importantly, vaccine-related metabolic correlates were shown to mirror immune activation states and, in some cases, predict immunogenicity and response durability. Conclusions: This review bridges metabolomics research in infectious disease pathogenesis and vaccine immunology across the NTD and non-NTD spectrum. By integrating these domains, it introduces the concept of “metabolic immuno-signatures” as predictive and translational tools for evaluating vaccine efficacy and immune response outcomes. Full article
(This article belongs to the Special Issue Review on Infectious Diseases)
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28 pages, 671 KB  
Review
In Situ Vaccination by Tumor Ablation: Principles and Prospects for Systemic Antitumor Immunity
by Tinatin Chikovani and Eli Magen
Vaccines 2025, 13(11), 1114; https://doi.org/10.3390/vaccines13111114 - 30 Oct 2025
Cited by 9 | Viewed by 3150
Abstract
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 [...] Read more.
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
(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)
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28 pages, 8441 KB  
Review
Recombinant Chimeric Virus-like Particles of Human Papillomavirus Produced by Distinct Cell Lineages: Potential as Prophylactic Nanovaccine and Therapeutic Drug Nanocarriers
by Cyntia Silva Oliveira, Dirce Sakauchi, Érica Akemi Kavati Sasaki and Aurora Marques Cianciarullo
Viruses 2025, 17(9), 1209; https://doi.org/10.3390/v17091209 - 4 Sep 2025
Cited by 2 | Viewed by 3669
Abstract
Antigenicity and immunogenicity define a potent immunogen in vaccinology. Nowadays, there are simplified platforms to produce nanocarriers for small-peptide antigen delivery, derived from various infectious agents for the treatment of a variety of diseases, based on virus-like particles (VLPs). They have good cell-penetrating [...] Read more.
Antigenicity and immunogenicity define a potent immunogen in vaccinology. Nowadays, there are simplified platforms to produce nanocarriers for small-peptide antigen delivery, derived from various infectious agents for the treatment of a variety of diseases, based on virus-like particles (VLPs). They have good cell-penetrating properties and protective action for target molecules from degradation. Human papillomavirus (HPV) causes anogenital warts and six types of cancer in infected women, men, or children, posing a challenge to global public health. The HPV capsid is composed of viral type-specific L1 and evolutionarily conserved L2 proteins. Produced in heterologous systems, the L1 protein can self-assemble into VLPs, nanoparticles sized around 50–60 nm, used as prophylactic vaccines. Devoid of the viral genome, they are safe for users, offering no risk of infection because VLPs do not replicate. The immune response induced by HPV VLPs is promoted by conformational viral epitopes, generating effective T- and B-cell responses. Produced in different cell systems, HPV16 L1 VLPs can be obtained on a large scale for use in mass immunization programs, which are well established nowadays. The expression of heterologous proteins was evaluated at various transfection times by transfecting cells with vectors encoding codon-optimized HPV16L1 and HPV16L2 genes. Immunological response induced by chimeric HPV16 L1/L2 VLP was evaluated through preclinical assays by antibody production, suggesting the potential of broad-spectrum protection against HPV as a prophylactic nanovaccine. These platforms can also offer promising therapeutic strategies, covering the various possibilities for complementary studies to develop potential preventive and therapeutic vaccines with broad-spectrum protection, using in silico new epitope selection and innovative nanotechnologies to obtain more effective immunobiologicals in combating HPV-associated cancers, influenza, hepatitis B and C, tuberculosis, human immunodeficiency virus (HIV), and many other illnesses. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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15 pages, 302 KB  
Review
Revolutionizing Veterinary Vaccines: Overcoming Cold-Chain Barriers Through Thermostable and Novel Delivery Technologies
by Rabin Raut, Roshik Shrestha, Ayush Adhikari, Arjmand Fatima and Muhammad Naeem
Appl. Microbiol. 2025, 5(3), 83; https://doi.org/10.3390/applmicrobiol5030083 - 19 Aug 2025
Cited by 8 | Viewed by 6883
Abstract
Veterinary vaccines are essential tools for controlling infectious and zoonotic diseases, safeguarding animal welfare, and ensuring global food security. However, conventional vaccines are hindered by cold-chain dependence, thermal instability, and logistical challenges, particularly in low- and middle-income countries (LMICs). This review explores next-generation [...] Read more.
Veterinary vaccines are essential tools for controlling infectious and zoonotic diseases, safeguarding animal welfare, and ensuring global food security. However, conventional vaccines are hindered by cold-chain dependence, thermal instability, and logistical challenges, particularly in low- and middle-income countries (LMICs). This review explores next-generation veterinary vaccines, emphasizing innovations in thermostability and delivery platforms to overcome these barriers. Recent advances in vaccine drying technologies, such as lyophilization and spray drying, have improved antigen stability and storage resilience, facilitating effective immunization in remote settings. Additionally, novel delivery systems, including nanoparticle-based formulations, microneedles, and mucosal routes (intranasal, aerosol, and oral), enhance vaccine efficacy, targeting immune responses at mucosal surfaces while minimizing invasiveness and cost. These approaches reduce reliance on cold-chain logistics, improve vaccine uptake, and enable large-scale deployment in field conditions. The integration of thermostable formulations with innovative delivery technologies offers scalable solutions to immunize livestock and aquatic species against major pathogens. Moreover, these strategies contribute significantly to One Health objectives by mitigating zoonotic spillovers, reducing antibiotic reliance, and supporting sustainable development through improved animal productivity. The emerging role of artificial intelligence (AI) in vaccine design—facilitating epitope prediction, formulation optimization, and rapid diagnostics—further accelerates vaccine innovation, particularly in resource-constrained environments. Collectively, the convergence of thermostability, advanced delivery systems, and AI-driven tools represents a transformative shift in veterinary vaccinology, with profound implications for public health, food systems, and global pandemic preparedness. Full article
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