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Keywords = precision vaccinology

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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 1444
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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33 pages, 2619 KB  
Review
Precision Adjuvant Strategies in Vaccine Development for Substance Use Disorders: Variability and Mechanistic Insights
by Yuanzhi Bian, Qiaoqiao Ci, Xin M. Luo and Chenming Zhang
Pharmaceutics 2025, 17(9), 1223; https://doi.org/10.3390/pharmaceutics17091223 - 20 Sep 2025
Cited by 4 | Viewed by 2260
Abstract
Substance use disorders (SUDs) remain a major global health challenge with limited treatment options and high relapse rates. Vaccines that induce drug-sequestering antibodies have shown promise, but their efficacy is hindered by the poor immunogenicity of small-molecule haptens. Adjuvants, substances that enhance immune [...] Read more.
Substance use disorders (SUDs) remain a major global health challenge with limited treatment options and high relapse rates. Vaccines that induce drug-sequestering antibodies have shown promise, but their efficacy is hindered by the poor immunogenicity of small-molecule haptens. Adjuvants, substances that enhance immune responses, are critical for overcoming this limitation and improving vaccine efficacy. This review synthesizes over two decades of preclinical and clinical research to guide rational adjuvant design for SUD vaccines. Five major adjuvant classes are examined: aluminum-salt adjuvants, emulsion adjuvants, toll-like receptor (TLR) agonists, protein immunopotentiators, and cytokine modulators. Their physicochemical properties, innate immune activation profiles, and applications in nicotine, stimulant, and opioid vaccines are discussed. Comparative analyses reveal pronounced drug-specific and carrier-specific variability. Case studies illustrate the superior performance of a complementary TLR-agonist pair in a nicotine nanovaccine versus its limited effect in oxycodone vaccines. They also reveal the differential efficacy of an oil-in-water emulsion adjuvant across antigen types. Four principles emerge: (i) no adjuvant is universally optimal; (ii) drug pharmacology influences immune signaling; (iii) adjuvant-carrier compatibility is important; (iv) complementary adjuvant pairings often outperform single agents. These insights support a precision-vaccinology paradigm that tailors adjuvant strategies to each drug class and the delivery vehicle, advancing the development of next-generation SUD vaccines. Full article
(This article belongs to the Section Biopharmaceutics)
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28 pages, 2489 KB  
Review
Role of the Virome in Vaccine-Induced Immunization
by Rossella Cianci, Mario Caldarelli, Paola Brani, Annalisa Bosi, Alessandra Ponti, Cristina Giaroni and Andreina Baj
Vaccines 2025, 13(9), 895; https://doi.org/10.3390/vaccines13090895 - 23 Aug 2025
Cited by 4 | Viewed by 2460
Abstract
The human virome—comprising viruses that can persist in a host, those that benefit the host, and those that remain latent—has gained increasing acceptance as a modulator of immune response toward vaccination. The factors known to influence vaccine efficacy include host genetics, age, and [...] Read more.
The human virome—comprising viruses that can persist in a host, those that benefit the host, and those that remain latent—has gained increasing acceptance as a modulator of immune response toward vaccination. The factors known to influence vaccine efficacy include host genetics, age, and bacterial microbiota, while the virome is a much less considered fourth dimension. This article reviews how components of the virome such as Torque Teno Virus (TTV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and bacteriophages impact both innate and adaptive immune responses, including mechanisms of immune pre-activation, trained immunity, and molecular mimicry from both beneficial and detrimental perspectives for vaccine-induced immunization. Emphasis is given to immunocompromised populations such as transplant recipients and those with HIV, where virome composition has been shown to correlate with vaccine responsiveness. Experimental models support clinical observations on how chronic viral exposures can either enhance or inhibit vaccine efficacy. Finally, we discuss virome-aware precision vaccinology and call for the integration of the virome in the development of immunization strategies, thus improving outcomes through customization. Full article
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29 pages, 5219 KB  
Article
Design and Validation of a Multi-Epitope mRNA Vaccine Construct Against Human Monkeypox Virus (hMPXV) by Annotating Protein of Intracellular Mature Virus (IMV) Form of hMPXV
by Mohammad Asrar Izhari, Siraj B. Alharthi, Raed A. Alharbi, Ahmad H. A. Almontasheri, Wael A. Alghamdi, Abdulmajeed Abdulghani A. Sindi, Ahmad Abdulmajed Salem, Ali Mahzari, Fahad Alghamdi and Ahmed R. A. Gosady
Biomedicines 2025, 13(6), 1439; https://doi.org/10.3390/biomedicines13061439 - 11 Jun 2025
Cited by 5 | Viewed by 3377
Abstract
Background: hMPXV poses a major public health risk due to its human-to-human transmissibility, severe complications, especially in immunocompromised individuals, and global spread, necessitating effective surveillance and stringent prophylactic measures to mitigate its colossal impact. Objective: The study aimed to annotate hMPXV(IMV) [...] Read more.
Background: hMPXV poses a major public health risk due to its human-to-human transmissibility, severe complications, especially in immunocompromised individuals, and global spread, necessitating effective surveillance and stringent prophylactic measures to mitigate its colossal impact. Objective: The study aimed to annotate hMPXV(IMV) proteins to propose a potential reverse vaccinology-based vaccine against hMPXV. Methods: The target MPXV(IMV) protein’s sequences, formatted in FASTA, were sourced from genome/proteome databases (BV-BRC and UniProt) (accessed on 6 November 2024), followed by CD-Hit-based redundancy removal. Epitope prediction for B-cells (lymphocytes), cytotoxic T-cells or cytotoxic T-lymphocytes (CTLs), and helper T-cells (HTLs) was executed using ABCpred, IEDB’s ANNs 4.0, and an artificial neural network-based alignment tool (NN-align 2.3)/ML-based tool (NetMHCII 2.3). Various immunoinformatics filters (antigenicity, toxicity, and allergenicity) were applied to substantiate the potency and safety of the formulated vaccine candidate. The constructed vaccine’s physiochemical and structural features (secondary and tertiary), with structural stability (confirmed by molecular docking followed by dynamic simulation with TLRs (TLR4 & TLR2) and MHCs), were determined. Additionally, cloning (using pET-28a(+) vector) was conducted to verify the vaccine’s expression potential and translation efficiency. The construct’s population coverage was also ascertained. Results: The MPXV-2-Beta vaccine constructs, of the six initially designed constructs, was identified as the most promising candidate, signifying nonallergenic profile and nontoxic features, with a predicted antigenicity score (PAS) = 0.7202, 407 residues, a molecular weight of 43,102.1 Da, pI of 9.2, and favorable stability parameters (AI: 65.65, GRAVY: −0.597, I-i: 25.92). It showed high solubility (score: 0.942). The ProSA Z-score of −9.38 confirmed the structural stability, reliability, and precision of the MPXV-2-Beta 3D model, which is comparable to experimental structures. Furthermore, 98.8% of all the residues nested within favored or allowed regions in a critical Ramachandran plot signified the model’s exceptional structural integrity and quality. Docking and dynamic simulation of MPXV-2-Beta with TLRs (TLR4 & TLR2) and MHCs demonstrated stiffer docking stability (strong polar and nonpolar interaction) and negative eigenvalue value (during dynamic simulation), suggesting its ability to enhance immune receptor activation under physiological conditions. MPXV-2-Beta was predicted to trigger a robust immune response (IR) with comprehensive world population coverage (98.55%, SD = 10.41). Conclusions: Based on the evaluated parameters, the MPXV-2-Beta designed in this study exhibited significant potential as an effective candidate against hMPXV. This study establishes a foundation for developing an efficient vaccine against hMPXV, requiring further experimental and clinical validation to confirm computational findings. Full article
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38 pages, 776 KB  
Review
Transforming Aquaculture through Vaccination: A Review on Recent Developments and Milestones
by Iosif Tammas, Konstantina Bitchava and Athanasios I. Gelasakis
Vaccines 2024, 12(7), 732; https://doi.org/10.3390/vaccines12070732 - 1 Jul 2024
Cited by 59 | Viewed by 14284
Abstract
Aquaculture has rapidly emerged as one of the fastest growing industries, expanding both on global and on national fronts. With the ever-increasing demand for proteins with a high biological value, the aquaculture industry has established itself as one of the most efficient forms [...] Read more.
Aquaculture has rapidly emerged as one of the fastest growing industries, expanding both on global and on national fronts. With the ever-increasing demand for proteins with a high biological value, the aquaculture industry has established itself as one of the most efficient forms of animal production, proving to be a vital component of global food production by supplying nearly half of aquatic food products intended for human consumption. As in classic animal production, the prevention of diseases constitutes an enduring challenge associated with severe economic and environmental repercussions. Nevertheless, remarkable strides in the development of aquaculture vaccines have been recently witnessed, offering sustainable solutions to persistent health-related issues challenging resilient aquaculture production. These advancements are characterized by breakthroughs in increased species-specific precision, improved vaccine-delivery systems, and innovations in vaccine development, following the recent advent of nanotechnology, biotechnology, and artificial intelligence in the -omics era. The objective of this paper was to assess recent developments and milestones revolving around aquaculture vaccinology and provide an updated overview of strengths, weaknesses, opportunities, and threats of the sector, by incorporating and comparatively discussing various diffuse advances that span across a wide range of topics, including emerging vaccine technologies, innovative delivery methods, insights on novel adjuvants, and parasite vaccine development for the aquaculture sector. Full article
(This article belongs to the Special Issue Fish Disease Occurrence and Immune Prevention and Control)
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15 pages, 3888 KB  
Review
Precision Vaccinology Approaches for the Development of Adjuvanted Vaccines Targeted to Distinct Vulnerable Populations
by Branden Lee, Etsuro Nanishi, Ofer Levy and David J. Dowling
Pharmaceutics 2023, 15(6), 1766; https://doi.org/10.3390/pharmaceutics15061766 - 19 Jun 2023
Cited by 11 | Viewed by 3702
Abstract
Infection persists as one of the leading global causes of morbidity and mortality, with particular burden at the extremes of age and in populations who are immunocompromised or suffer chronic co-morbid diseases. By focusing discovery and innovation efforts to better understand the phenotypic [...] Read more.
Infection persists as one of the leading global causes of morbidity and mortality, with particular burden at the extremes of age and in populations who are immunocompromised or suffer chronic co-morbid diseases. By focusing discovery and innovation efforts to better understand the phenotypic and mechanistic differences in the immune systems of diverse vulnerable populations, emerging research in precision vaccine discovery and development has explored how to optimize immunizations across the lifespan. Here, we focus on two key elements of precision vaccinology, as applied to epidemic/pandemic response and preparedness, including (a) selecting robust combinations of adjuvants and antigens, and (b) coupling these platforms with appropriate formulation systems. In this context, several considerations exist, including the intended goals of immunization (e.g., achieving immunogenicity versus lessening transmission), reducing the likelihood of adverse reactogenicity, and optimizing the route of administration. Each of these considerations is accompanied by several key challenges. On-going innovation in precision vaccinology will expand and target the arsenal of vaccine components for protection of vulnerable populations. Full article
(This article belongs to the Special Issue Designing and Developing the Next Generation of Vaccine Adjuvants)
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10 pages, 133 KB  
Review
From Antigen Delivery System to Adjuvanticy: The Board Application of Nanoparticles in Vaccinology
by Diana Boraschi and Paola Italiani
Vaccines 2015, 3(4), 930-939; https://doi.org/10.3390/vaccines3040930 - 5 Nov 2015
Cited by 56 | Viewed by 8967
Abstract
In the last years, nanotechnologies have raised great interest because of the potential applications of engineered nanoparticles in nanomedicine (i.e., in vaccination, in diagnostic imaging procedures, and as therapeutic drug delivery systems). The use of nanoparticles in medicine has brought about [...] Read more.
In the last years, nanotechnologies have raised great interest because of the potential applications of engineered nanoparticles in nanomedicine (i.e., in vaccination, in diagnostic imaging procedures, and as therapeutic drug delivery systems). The use of nanoparticles in medicine has brought about the issue of their interaction with the immune system for two main reasons: first, understanding how long nanomedicines could persist in the organism and exert their beneficial effects before being recognized and eliminated by our defensive systems; second, understanding how the immune responses can be modulated by nanoparticles in order to obtain optimal effects. This issue is crucial in vaccine formulations based on the use of nanoparticles, which can operate both as a delivery system to enhance antigen processing and as an immunostimulatory adjuvant to induce and amplify protective immunity, in part because of their ability to activate the inflammasome and induce the maturation of interleukin 1β. Nanoparticles can be excellent adjuvants due to their biocompatibility and their physicochemical properties (e.g., size, shape, and surface charge), which can be tailored to obtain different immunological effects. This review provides an overview of recent strategies for the use of nanoparticles as promising/attractive adjuvants for novel prophylactic and therapeutic vaccines. The use of nanovaccines, with their practically infinite possibilities of specific design, could open the way to precision vaccinology, i.e., vaccine formulations tailored on the individual immune reactivity status. Full article
(This article belongs to the Special Issue Nanoparticle-Based Vaccines)
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