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Keywords = Capsid-targeted viral inactivation

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20 pages, 986 KiB  
Review
Past, Present, and Future of Viral Vector Vaccine Platforms: A Comprehensive Review
by Justin Tang, Md Al Amin and Jian L. Campian
Vaccines 2025, 13(5), 524; https://doi.org/10.3390/vaccines13050524 - 15 May 2025
Viewed by 2495
Abstract
Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often [...] Read more.
Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often superior to what traditional inactivated or subunit vaccines can achieve. This has accelerated their application to a wide array of pathogens and disease targets, from well-established threats like HIV and malaria to emerging infections such as Ebola, Zika, and SARS-CoV-2. The COVID-19 pandemic further highlighted the agility of viral vector platforms, with several adenovirus-based vaccines quickly authorized and deployed on a global scale. Despite these advances, significant challenges remain. One major hurdle is pre-existing immunity against commonly used vector backbones, which can blunt vaccine immunogenicity. Rare but serious adverse events, including vector-associated inflammatory responses and conditions like vaccine-induced immune thrombotic thrombocytopenia (VITT), have raised important safety considerations. Additionally, scaling up manufacturing, ensuring consistency in large-scale production, meeting rigorous regulatory standards, and maintaining equitable global access to these vaccines present profound logistical and ethical dilemmas. In response to these challenges, the field is evolving rapidly. Sophisticated engineering strategies, such as integrase-defective lentiviral vectors, insect-specific flaviviruses, chimeric capsids to evade neutralizing antibodies, and plug-and-play self-amplifying RNA approaches, seek to bolster safety, enhance immunogenicity, circumvent pre-existing immunity, and streamline production. Lessons learned from the COVID-19 pandemic and prior outbreaks are guiding the development of platform-based approaches designed for rapid deployment during future public health emergencies. This review provides an exhaustive, in-depth examination of the historical evolution, immunobiological principles, current platforms, manufacturing complexities, regulatory frameworks, known safety issues, and future directions for viral vector-based vaccines. Full article
(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)
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17 pages, 6448 KiB  
Article
The Protective Effects and Immunological Responses Induced by a Carboxymethyl Cellulose Microcapsule-Coated Inactivated Vaccine Against Largemouth Bass Ranavirus (LMBRaV) in Largemouth Bass (Micropterus salmoides)
by Jiale Zhai, Yuding Fan, Yiqun Li, Mingyang Xue, Yan Meng, Zhenyu Huang, Jie Ma, Yong Zhou and Nan Jiang
Vaccines 2025, 13(3), 233; https://doi.org/10.3390/vaccines13030233 - 25 Feb 2025
Viewed by 827
Abstract
Background: Epizootics of largemouth bass ranavirus (LMBRaV) in largemouth bass (Micropterus salmoides) populations are associated with elevated mortality and significant financial losses. Given the lack of effective and safe medication to treat this disease, oral vaccination, which directly targets the intestinal [...] Read more.
Background: Epizootics of largemouth bass ranavirus (LMBRaV) in largemouth bass (Micropterus salmoides) populations are associated with elevated mortality and significant financial losses. Given the lack of effective and safe medication to treat this disease, oral vaccination, which directly targets the intestinal mucosal immune system, is crucial for disease resistance. Methods: This study utilized carboxymethyl cellulose (CMC) to coat LMBRaV inactivated vaccine (LIV) (micro-CMC@LIV). The morphology and characteristics of the CMC microcapsules were determined. In vitro simulated gastric and intestinal conditions were used to validate that the microcapsules could tolerate gastric conditions and subsequently release their contents in the intestinal tract. This was confirmed using CMC-coated coumarin 6 (C6) fluorescence microcapsules. Results: After the oral administration of micro-CMC@LIV, the detection of LMBRaV major capsid protein confirmed effective antigen release and absorption in the midgut and hindgut. Neutralizing antibody titers were significantly higher (1:81.71) in the micro-CMC@LIV group compared to the uncoated vaccine group (1:21.69). The expression of genes linked to the innate and adaptive immune systems was upregulated post-micro-CMC@LIV treatment. Following the LMBRaV challenge, the micro-CMC@LIV group exhibited a relative percent survival (RPS) of 82.14%, significantly higher than the uncoated vaccine group (61.61%). Droplet digital PCR analysis revealed significantly lower viral loads in the liver, spleen, and head kidney of the micro-CMC@LIV group compared to the control group and the uncoated vaccine group. Conclusions: These results collectively suggest that the CMC-coated LIV can be effectively delivered to the intestinal tract and induce robust antibody and immune responses, providing a reliable method for preventing and controlling LMBRaV disease in the largemouth bass industry. Full article
(This article belongs to the Special Issue Next-Generation Vaccines for Animal Infectious Diseases)
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17 pages, 2141 KiB  
Article
Long-Term Protection in Atlantic Salmon (Salmo salar) to Pancreas Disease (PD) Can Be Achieved Through Immunization with Genetically Modified, Live Attenuated Salmonid Alphavirus 3
by Stine Braaen, Øystein Wessel, Håvard Bjørgen and Espen Rimstad
Vaccines 2025, 13(2), 190; https://doi.org/10.3390/vaccines13020190 - 15 Feb 2025
Viewed by 760
Abstract
Background: Pancreas disease (PD) is a serious disease in European salmonid aquaculture caused by salmonid alphavirus (SAV), of which six genotypes (SAV1–6) have been described. The use of inactivated virus and DNA PD vaccines is common in marine salmonid aquaculture and has [...] Read more.
Background: Pancreas disease (PD) is a serious disease in European salmonid aquaculture caused by salmonid alphavirus (SAV), of which six genotypes (SAV1–6) have been described. The use of inactivated virus and DNA PD vaccines is common in marine salmonid aquaculture and has contributed to a reduction of the occurrence of disease; however, outbreaks are still frequent. Methods: In this study, we compared the long-term protection after immunization of Atlantic salmon (Salmo salar) with three different clones of attenuated infectious SAV3. The clones were made by site-directed mutagenesis targeting the glycoprotein E2 to disrupt the viral attachment and/or nuclear localization signal (NLS) of the capsid protein to disrupt the viral suppression of cellular nuclear-cytosol trafficking. The resulting clones (Clones 1–3) were evaluated after injection of Atlantic salmon for infection dynamics, genetic stability, transmission, and protection against a subsequent SAV3 challenge. Results: Attenuated clones demonstrated reduced virulence, as indicated by lower viral RNA loads, diminished transmission to cohabitant fish, and minimal clinical symptoms compared to the virulent wild-type virus. The clones mutated in both capsid and E2 exhibited the most attenuation, observed as rapid clearing of the infection and showing little transmission, while the clone with glycoprotein E2 mutations displayed greater residual virulence but provided stronger protection, seen as reduced viral loads upon subsequent challenge with SAV3. Despite their attenuation, all viral clones caused significant reductions in weight gain. Conclusions: Despite promising attenuation and protection, this study highlights the trade-offs between virulence and immunogenicity in live vaccine design. Concerns over environmental risks, such as the shedding of genetically modified virus, necessitate further evaluation. Future efforts should optimize vaccine candidates to balance attenuation, immunogenicity, and minimal side effects. Full article
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22 pages, 2158 KiB  
Article
Broad-Spectrum, Potent, and Durable Ceria Nanoparticles Inactivate RNA Virus Infectivity by Targeting Virion Surfaces and Disrupting Virus–Receptor Interactions
by Candace R. Fox, Kritika Kedarinath, Craig J. Neal, Jeremy Sheiber, Elayaraja Kolanthai, Udit Kumar, Christina Drake, Sudipta Seal and Griffith D. Parks
Molecules 2023, 28(13), 5190; https://doi.org/10.3390/molecules28135190 - 4 Jul 2023
Cited by 5 | Viewed by 2734
Abstract
There is intense interest in developing long-lasting, potent, and broad-spectrum antiviral disinfectants. Ceria nanoparticles (CNPs) can undergo surface redox reactions (Ce3+ ↔ Ce4+) to generate ROS without requiring an external driving force. Here, we tested the mechanism behind our prior [...] Read more.
There is intense interest in developing long-lasting, potent, and broad-spectrum antiviral disinfectants. Ceria nanoparticles (CNPs) can undergo surface redox reactions (Ce3+ ↔ Ce4+) to generate ROS without requiring an external driving force. Here, we tested the mechanism behind our prior finding of potent inactivation of enveloped and non-enveloped RNA viruses by silver-modified CNPs, AgCNP1 and AgCNP2. Treatment of human respiratory viruses, coronavirus OC43 and parainfluenza virus type 5 (PIV5) with AgCNP1 and 2, respectively, prevented virus interactions with host cell receptors and resulted in virion aggregation. Rhinovirus 14 (RV14) mutants were selected to be resistant to inactivation by AgCNP2. Sequence analysis of the resistant virus genomes predicted two amino acid changes in surface-located residues D91V and F177L within capsid protein VP1. Consistent with the regenerative properties of CNPs, surface-applied AgCNP1 and 2 inactivated a wide range of structurally diverse viruses, including enveloped (OC43, SARS-CoV-2, and PIV5) and non-enveloped RNA viruses (RV14 and feline calicivirus; FCV). Remarkably, a single application of AgCNP1 and 2 potently inactivated up to four sequential rounds of virus challenge. Our results show broad-spectrum and long-lasting anti-viral activity of AgCNP nanoparticles, due to targeting of viral surface proteins to disrupt interactions with cellular receptors. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Drugs Discovery)
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17 pages, 2429 KiB  
Article
Development of Highly Efficient Resistance to Beet Curly Top Iran Virus (Becurtovirus) in Sugar Beet (B. vulgaris) via CRISPR/Cas9 System
by Kubilay Yıldırım, Musa Kavas, İlkay Sevgen Küçük, Zafer Seçgin and Çiğdem Gökcek Saraç
Int. J. Mol. Sci. 2023, 24(7), 6515; https://doi.org/10.3390/ijms24076515 - 30 Mar 2023
Cited by 13 | Viewed by 3177
Abstract
Beet Curly Top Iran Virus (BCTIV, Becurtovirus) is a dominant and widespread pathogen responsible for great damage and yield reduction in sugar beet production in the Mediterranean and Middle East. CRISPR-based gene editing is a versatile tool that has been successfully used [...] Read more.
Beet Curly Top Iran Virus (BCTIV, Becurtovirus) is a dominant and widespread pathogen responsible for great damage and yield reduction in sugar beet production in the Mediterranean and Middle East. CRISPR-based gene editing is a versatile tool that has been successfully used in plants to improve resistance against many viral pathogens. In this study, the efficiency of gRNA/Cas9 constructs targeting the expressed genes of BCTIV was assessed in sugar beet leaves by their transient expression. Almost all positive control sugar beets revealed systemic infection and severe disease symptoms (90%), with a great biomass reduction (68%) after BCTIV agroinoculation. On the other hand, sugar beets co-agronioculated with BCTIV and gRNA/Cas9 indicated much lower systemic infection (10–55%), disease symptoms and biomass reduction (13–45%). Viral inactivation was also verified by RCA and qPCR assays for gRNA/Cas9 treated sugar beets. PCR-RE digestion and sequencing assays confirmed the gRNA/Cas9-mediated INDEL mutations at the target sites of the BCTIV genome and represented high efficiencies (53–88%), especially for those targeting BCTIV’s movement gene and its overlapping region between capsid and ssDNA regulator genes. A multiplex CRISPR approach was also tested. The most effective four gRNAs targeting all the genes of BCTIV were cloned into a Cas9-containing vector and agroinoculated into virus-infected sugar beet leaves. The results of this multiplex CRISPR system revealed almost complete viral resistance with inhibition of systemic infection and mutant escape. This is the first report of CRSIPR-mediated broad-spectrum resistance against Becurtovirus in sugar beet. Full article
(This article belongs to the Special Issue Crop Stress Biology and Molecular Breeding 3.0)
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11 pages, 1421 KiB  
Article
Transiently Transfected Mammalian Cell Cultures: An Adaptable and Effective Platform for Virus-like Particle-Based Vaccines against Foot-and-Mouth Disease Virus
by Michael Puckette, Victoria Primavera, Erica Martel, Jose Barrera, William Hurtle, Benjamin Clark, Barbara Kamicker, Mariceny Zurita, David Brake and John Neilan
Viruses 2022, 14(5), 989; https://doi.org/10.3390/v14050989 - 7 May 2022
Cited by 10 | Viewed by 3487
Abstract
RNA viruses, such as foot-and-mouth disease virus (FMDV), have error-prone replication resulting in the continuous emergence of new viral strains capable of evading current vaccine coverage. Vaccine formulations must be regularly updated, which is both costly and technically challenging for many vaccine platforms. [...] Read more.
RNA viruses, such as foot-and-mouth disease virus (FMDV), have error-prone replication resulting in the continuous emergence of new viral strains capable of evading current vaccine coverage. Vaccine formulations must be regularly updated, which is both costly and technically challenging for many vaccine platforms. In this report, we describe a plasmid-based virus-like particle (VLP) production platform utilizing transiently transfected mammalian cell cultures that combines both the rapid response adaptability of nucleic-acid-based vaccines with the ability to produce intact capsid epitopes required for immunity. Formulated vaccines which employed this platform conferred complete protection from clinical foot-and-mouth disease in both swine and cattle. This novel platform can be quickly adapted to new viral strains and serotypes through targeted exchanges of only the FMDV capsid polypeptide nucleic acid sequences, from which processed structural capsid proteins are derived. This platform obviates the need for high biocontainment manufacturing facilities to produce inactivated whole-virus vaccines from infected mammalian cell cultures, which requires upstream expansion and downstream concentration of large quantities of live virulent viruses. Full article
(This article belongs to the Special Issue Global Foot-and-Mouth Disease Control)
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1 pages, 152 KiB  
Abstract
Cell Surface-Expressed GPI-Anchored Peptides from the CHR Domain of gp41 Are Potent Inhibitors of HIV-1 Fusion
by Aleksandra Maslennikova, Dmitriy Komkov, Anastasia Zotova and Dmitriy Mazurov
Proceedings 2020, 50(1), 70; https://doi.org/10.3390/proceedings2020050070 - 16 Jun 2020
Viewed by 1430
Abstract
Current antiretroviral therapy efficiently suppresses viral replication but cannot eliminate latent HIV reservoirs. Moreover, the associated high costs, side effects, and drug resistance have stimulated a need for the development of alternative methods of HIV-1/AIDS treatment, such as peptide inhibitors or gene editing. [...] Read more.
Current antiretroviral therapy efficiently suppresses viral replication but cannot eliminate latent HIV reservoirs. Moreover, the associated high costs, side effects, and drug resistance have stimulated a need for the development of alternative methods of HIV-1/AIDS treatment, such as peptide inhibitors or gene editing. Recently, we have developed Surface Oligopeptide knock-in for Rapid Target Selection (SORTS), a method for the rapid selection of CRISPR/Cas9 gene-edited cells via knock-in of the Flag and HA epitope tags embedded into the shortest GPI-protein, CD52. By targeting the capsid region of the HIV-1 genome, we demonstrate that SORTS can be applied in provirus eradication. However, the cells with inactivated provirus will be susceptible to HIV re-infection. We hypothesized that knocking in one of the peptides from the CHR-domain of gp41, which are known potent inhibitors of HIV-1 fusion, instead of the epitope tag, will provide “post-curable” HIV-1 resistance. While these peptides were extensively studied as soluble substances, their inhibitory effects on HIV after expression on cell surfaces via GPI-anchor are largely unknown. In this study, we established HEK293T/CD4/R5 and Raji/CD4/R5 HIV-1 permissive cell lines that stably expressed one of the gp41 peptides C34, MT-C34, MT-C34-R, and MT34-15D, or alfa-helix mimetics HP23L, p52, and MT-WQ-IDL. For cell surface delivery, the indicated peptides were embedded into the CD52 molecule, and upstream GFP was used to select transformed cells. Using a single-cycle replication assay with the inLuc reporter vector and different Envs, we demonstrated that C34-based GPI-anchored peptides inhibited both cell-free and cell-to-cell HIV-1 infection by at least two orders of magnitude. With the exception of HP23L, the alfa-helix mimetics were less potent inhibitors. Thus, peptides from gp41 associated with lipid rafts and exerted a strong inhibitory activity which can far exceed that determined for soluble peptides, but this should be tested further. Full article
(This article belongs to the Proceedings of Viruses 2020—Novel Concepts in Virology)
16 pages, 5656 KiB  
Article
Photodynamic Inactivation of Herpes Simplex Viruses
by Andrea L.-A. Monjo, Eric S. Pringle, Mackenzie Thornbury, Brett A. Duguay, Susan M. A. Monro, Marc Hetu, Danika Knight, Colin G. Cameron, Sherri A. McFarland and Craig McCormick
Viruses 2018, 10(10), 532; https://doi.org/10.3390/v10100532 - 29 Sep 2018
Cited by 34 | Viewed by 9169
Abstract
Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs [...] Read more.
Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species that inactivate microorganisms. The botanical plant extract OrthoquinTM is a powerful photosensitizer with antimicrobial properties. Here we report that Orthoquin also has antiviral properties. Photoactivated Orthoquin inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection of target cells in a dose-dependent manner across a broad range of sub-cytotoxic concentrations. HSV inactivation required direct contact between Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect. Orthoquin did not cause appreciable damage to viral capsids or premature release of viral genomes, as measured by qPCR for the HSV-1 genome. By contrast, immunoblotting for HSV-1 antigens in purified virion preparations suggested that higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that altered protein mobility or antigen detection. Orthoquin PDI also inhibited the non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin-mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light-independent. Together, these findings suggest that the broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins. Full article
(This article belongs to the Special Issue Recent Advances of Natural Products in HSV Research)
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13 pages, 1348 KiB  
Review
Capsid-Targeted Viral Inactivation: A Novel Tactic for Inhibiting Replication in Viral Infections
by Xingcui Zhang, Renyong Jia, Jiakun Zhou, Mingshu Wang, Zhongqiong Yin and Anchun Cheng
Viruses 2016, 8(9), 258; https://doi.org/10.3390/v8090258 - 21 Sep 2016
Cited by 12 | Viewed by 8181
Abstract
Capsid-targeted viral inactivation (CTVI), a conceptually powerful new antiviral strategy, is attracting increasing attention from researchers. Specifically, this strategy is based on fusion between the capsid protein of a virus and a crucial effector molecule, such as a nuclease (e.g., staphylococcal nuclease, Barrase, [...] Read more.
Capsid-targeted viral inactivation (CTVI), a conceptually powerful new antiviral strategy, is attracting increasing attention from researchers. Specifically, this strategy is based on fusion between the capsid protein of a virus and a crucial effector molecule, such as a nuclease (e.g., staphylococcal nuclease, Barrase, RNase HI), lipase, protease, or single-chain antibody (scAb). In general, capsid proteins have a major role in viral integration and assembly, and the effector molecule used in CTVI functions to degrade viral DNA/RNA or interfere with proper folding of viral key proteins, thereby affecting the infectivity of progeny viruses. Interestingly, such a capsid–enzyme fusion protein is incorporated into virions during packaging. CTVI is more efficient compared to other antiviral methods, and this approach is promising for antiviral prophylaxis and therapy. This review summarizes the mechanism and utility of CTVI and provides some successful applications of this strategy, with the ultimate goal of widely implementing CTVI in antiviral research. Full article
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