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Hannoun, Cl. "Vaccins antiviraux." Médecine et Maladies Infectieuses 18 (November 1988): 603–10. http://dx.doi.org/10.1016/s0399-077x(88)80169-0.
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Sacoun, Esther. "Actualités sur les nouveaux vaccins antiviraux : grippe, papillomavirus, zona." Actualités Pharmaceutiques 50, no. 505 (April 2011): 38–39. http://dx.doi.org/10.1016/s0515-3700(11)70939-9.
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Sacoun, Esther. "Actualités sur les nouveaux vaccins antiviraux : grippe, papillomavirus, zona." Option/Bio 22, no. 450 (March 2011): 4–5. http://dx.doi.org/10.1016/s0992-5945(11)70680-8.
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Bertholom, Chantal. "Traitement et prévention des infections herpétiques : nouveaux antiviraux et vaccins." Option/Bio 26, no. 530 (July 2015): 16–17. http://dx.doi.org/10.1016/s0992-5945(15)30238-5.
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Wang, Yi, Yu-yuan Li, and Wen Guo. "Original Article .The Optimal Allocation of Investment between Antivirals and Vaccines for Influenza Pandemic Preparedness Planning." Infection International 1, no. 1 (March 1, 2012): 25–33. http://dx.doi.org/10.1515/ii-2017-0004.
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Abstract Objectives To investigate that given a fixed amount of financial resources, what is the optimal combination of vaccine and antiviral stockpiles in terms of minimizing the attack rate. Methods Mathematic modeling was used to simulate the dynamics that with fixed influenza pandemic budget. Different budget conditions were observed if the combination changed. Framework between vaccines and antivirals was introduced by taking into account the uncertainty in vaccine and antiviral efficacy. Results Given a fixed budget, different budget allocations between vaccines and antivirals stockpile gave different attack rates. When the price of vaccine was lower than or similar with the antivirals, the attack rate increased with increasing investment in antiviral. But if the price of the vaccine was higher than the antivirals, the attack rate may not decrease with increasing investment in vaccine. Fixed the vaccine effectiveness, higher effectiveness of antiviral got a lower attack rate.When both antiviral and vaccine were with 50% probability of effectiveness, the attack rate changed by antiviral stockpile with a same pattern as they were with 100% efficacy probability, even it has a higher attack rate. Conclusions Assume the antivirals have 100% probability to be effective, budget was limited to a fix number, then in any event, population should stockpile a small amount of antivirals such that if the post-vaccination reproductive number turns out to be near 1, the additional intervention may further reduce the reproductive number to <1 and prevent the epidemic. Under the fixed budget, the price of the vaccines and antivirals will strongly affect the strategy of the stockpile allocation. When the price of vaccine is comparative lower, more investment of vaccine is better for the pandemic control, but if the vaccine price is too high then more investment in antiviral may be better. We found that attack rates and the optimal budget allocation depend on the probability to be effective of vaccine and antivirals.
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Gervelmeyer, A., H. Abu Ajarnijeh, E. Bani Younis, O. Anasweh, N. Bzour, R. Akasheh, Peter-Henning Clausen, C. Staak, and G. Monreal. "Production d'anticorps de jaune d'oeuf antiviraux spécifiques pour le diagnostic de la maladie de Newcastle, de la bronchite infectieuse et de la maladie de Gumboro par le test d'immunofluorescence directe." Revue d’élevage et de médecine vétérinaire des pays tropicaux 51, no. 1 (January 1, 1998): 5–9. http://dx.doi.org/10.19182/remvt.9652.
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Les possibilités d'utilisation d'anticorps de jaune d'oeuf (IgY) pour la détection des virus de la maladie de Newcastle (NDV), de la bronchite infectieuse (IBDV) et de la maladie de Gumboro (IBDV) par le test d'immunofluorescence directe ont été examinées. Des poules pondeuses ont été immunisées avec différents vaccins commerciaux à NDV, IBV et IBDV inactivés. L'immunisation a donné des titres élevés d'anticorps spécifiques dans le jaune d'oeuf à partir de 4 à 8 semaines après l'immunisation initiale, et ce durant une période d'environ 20 semaines. Les IgY ont été extraites du jaune d'oeuf par précipitation au sulfate d'ammonium, puis purifiées par la méthode de chromatographie d'affinité, donnant 1,46 mg d'IgY spécifique par jaune d'oeuf en moyenne. Après marquage avec l'isothiocyanate de fluorescéine (FITC) la sensibilité et la spécificité des conjugués ont été évaluées sur des cultures cellulaires sur des lamelles couvre-objets. Dans le test d'immunofluorescence directe, les conjugués dilués au 1 : 8 ou au 1 : 4 avec du PBS réagissaient spécifiquement avec l'antigène homologue dans des calques d'organes de poussins infectés expérimentalement et dans des cultures cellulaires sur des lamelles couvre-objets. Aucune réaction n'a été observée avec des antigènes hétérologues. La fluorescence non spécifique était facilement éliminée par une absorption avec de la poudre de foie. En conclusion, ces résultats montrent que les IgY marquées avec FITC peuvent être produites en grandes quantités de manière facile et économique. Pour le diagnostic de NDV, IBV et IBDV, les anticorps de jaune d'oeuf constituent donc une excellente alternative à la production d'anticorps fluorescents à partir du sang de lapins ou de poules, notamment pour les laboratoires ayant des moyens financiers limités.
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KRAMER, S. C., and S. BANSAL. "Assessing the use of antiviral treatment to control influenza." Epidemiology and Infection 143, no. 8 (October 2, 2014): 1621–31. http://dx.doi.org/10.1017/s0950268814002520.
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SUMMARYVaccines are the cornerstone of influenza control policy, but can suffer from several drawbacks. Seasonal influenza vaccines are prone to production problems and low efficacies, while pandemic vaccines are unlikely to be available in time to slow a rapidly spreading global outbreak. Antiviral therapy was found to be beneficial during the influenza A(H1N1)pdm09 pandemic even with limited use; however, antiviral use has decreased further since then. We sought to determine the role antiviral therapy can play in pandemic and seasonal influenza control using conservative estimates of antiviral efficacy, and to assess if conservative but targeted strategies could be employed to optimize the use of antivirals. Using an age-structured contact network model for an urban population, we compared the transmission-blocking ability of a conservative antiviral therapy strategy to the susceptibility-reducing effects of a robust influenza vaccine. Our results show that while antiviral therapy cannot replace a robust influenza vaccine, it can play a role in reducing attack rates and eliminating outbreaks, and could significantly reduce public health burden when vaccine is either unavailable or ineffective. We also found that antiviral therapy, by treating those who are infected, is naturally a highly optimized strategy, and need not be improved upon with expensive targeted campaigns.
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Nuwarda, Rina Fajri, Abdulsalam Abdullah Alharbi, and Veysel Kayser. "An Overview of Influenza Viruses and Vaccines." Vaccines 9, no. 9 (September 17, 2021): 1032. http://dx.doi.org/10.3390/vaccines9091032.
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Influenza remains one of the major public health concerns because it causes annual epidemics and can potentially instigate a global pandemic. Numerous countermeasures, including vaccines and antiviral treatments, are in use against seasonal influenza infection; however, their effectiveness has always been discussed due to the ongoing resistance to antivirals and relatively low and unpredictable efficiency of influenza vaccines compared to other vaccines. The growing interest in vaccines as a promising approach to prevent and control influenza may provide alternative vaccine development options with potentially increased efficiency. In addition to currently available inactivated, live-attenuated, and recombinant influenza vaccines on the market, novel platforms such as virus-like particles (VLPs) and nanoparticles, and new vaccine formulations are presently being explored. These platforms provide the opportunity to design influenza vaccines with improved properties to maximize quality, efficacy, and safety. The influenza vaccine manufacturing process is also moving forward with advancements relating to egg- and cell-based production, purification processes, and studies into the physicochemical attributes and vaccine degradation pathways. These will contribute to the design of more stable, optimized vaccine formulations guided by contemporary analytical testing methods and via the implementation of the latest advances in the field.
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Norshidah, Harun, Ramachandran Vignesh, and Ngit Shin Lai. "Updates on Dengue Vaccine and Antiviral: Where Are We Heading?" Molecules 26, no. 22 (November 9, 2021): 6768. http://dx.doi.org/10.3390/molecules26226768.
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Approximately 100–400 million people from more than 100 countries in the tropical and subtropical world are affected by dengue infections. Recent scientific breakthroughs have brought new insights into novel strategies for the production of dengue antivirals and vaccines. The search for specific dengue inhibitors is expanding, and the mechanisms for evaluating the efficacy of novel drugs are currently established, allowing for expedited translation into human trials. Furthermore, in the aftermath of the only FDA-approved vaccine, Dengvaxia, a safer and more effective dengue vaccine candidate is making its way through the clinical trials. Until an effective antiviral therapy and licensed vaccine are available, disease monitoring and vector population control will be the mainstays of dengue prevention. In this article, we highlighted recent advances made in the perspectives of efforts made recently, in dengue vaccine development and dengue antiviral drug.
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Murray, Jackelyn, David E. Martin, Fred D. Sancilio, and Ralph A. Tripp. "Antiviral Activity of Probenecid and Oseltamivir on Influenza Virus Replication." Viruses 15, no. 12 (November 30, 2023): 2366. http://dx.doi.org/10.3390/v15122366.
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Influenza can cause respiratory infections, leading to significant morbidity and mortality in humans. While current influenza vaccines offer varying levels of protection, there remains a pressing need for effective antiviral drugs to supplement vaccine efforts. Currently, the FDA-approved antiviral drugs for influenza include oseltamivir, zanamivir, peramivir, and baloxavir marboxil. These antivirals primarily target the virus, making them vulnerable to drug resistance. In this study, we evaluated the efficacy of the neuraminidase inhibitor, oseltamivir, against probenecid, which targets the host cells and is less likely to engender resistance. Our results show that probenecid has superior antiviral efficacy compared to oseltamivir in both in vitro replication assays and in vivo mouse models of influenza infection.
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Moss, Ronald B. "2009H1N1 Influenza in Immunocompetent and Immunocompromised Patients." Infectious Diseases: Research and Treatment 5 (January 2012): IDRT.S9226. http://dx.doi.org/10.4137/idrt.s9226.
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The treatment and prevention of influenza virus infection has been associated with two major challenges that are exemplified by 2009H1N1 as well as previous pandemics. The constant evolutionary pressure on the influenza virus can result in novel strains which may not be optimally protected by vaccines or currently approved antivirals. Selection for antiviral resistance mutations can occur over time. Prolonged virus shedding, selection for resistance mutations, and cross resistance, can be exacerbated and problematic in immunocompromised patients. This review will cover 2009H1N1 infection in immuno-competent and immunocompromised individuals. Influenza continues to be a major public health concern and these challenges make influenza a suitable area for new vaccine and antiviral approaches.
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Mahmood, Nasir, Sarah Bushra Nasir, and Kathleen Hefferon. "Plant-Based Drugs and Vaccines for COVID-19." Vaccines 9, no. 1 (December 30, 2020): 15. http://dx.doi.org/10.3390/vaccines9010015.
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The coronavirus SARS-CoV-2 has turned our own health and the world economy upside down. While several vaccine candidates are currently under development, antivirals with the potential to limit virus transmission or block infection are also being explored. Plant production platforms are being used to generate vaccines and antiviral proteins inexpensively and at mass scale. The following review discusses the biology and origins of the current coronavirus pandemic, and describes some of the conventional, synthetic, and plant-based approaches to address the challenge that it presents to our way of life.
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Mahendran, Manishaa Sri, Sinouvassane Djearamane, Ling Shing Wong, Govindaraju Kasivelu, and Anto Cordelia Tanislaus Antony Dhanapal. "ANTIVIRAL PROPERTIES OF MICROALGAE AND CYANOBACTERIA." Journal of Experimental Biology and Agricultural Sciences 9, Spl-1- GCSGD_2020 (March 25, 2021): S43—S48. http://dx.doi.org/10.18006/2021.9(spl-1-gcsgd_2020).s43.s48.
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The recent outbreak of Corona Virus Disease (COVID-19) and the surge in accelerating the development of a vaccine to fight against the SARS-CoV-2 virus has imposed greater challenges to humanity worldwide. There is lack of research into the production of effective vaccines and methods of treatment against viral infections. As of now, strategies encompassing antiviral drugs and corticosteroids alongside mechanical respiratory treatment are in practice as frontline treatments. Though studies have reported that microalgae possess antiviral properties, only a few cases have presented the existence of antiviral compounds such as algal polysaccharides, lectins, aggluttinins, scytovirin, algal lipids such as sulfoquinovosyldiacylglycerol (SQDG), monogalactosyldiacylglycerides (MGDG) and digalactosyldiacylglycerides (DGDG), and algal biopigments especially chlorophyll analogues, marennine, phycobiliproteins, phycocyanin, phycoerythrin and allophycocyanin that are derived from marine and freshwater microalgae. Given the chemodiversity of bioactive compounds from microalgae and the present scenario, algal biotechnology is seen as a prospective source of antiviral and anti-inflammatory compounds that can be used to develop antiviral agents. Microalgae with potential as antivirals and microalgae derived functional compounds to treat viral diseases are summarized and can be used as a reference in developing algae-derived antivirals to treat SARS-CoV-2 and other similar viruses.
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Gudima, Georgii, Ilya Kofiadi, Igor Shilovskiy, Dmitry Kudlay, and Musa Khaitov. "Antiviral Therapy of COVID-19." International Journal of Molecular Sciences 24, no. 10 (May 16, 2023): 8867. http://dx.doi.org/10.3390/ijms24108867.
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Since the beginning of the COVID-19 pandemic, the scientific community has focused on prophylactic vaccine development. In parallel, the experience of the pharmacotherapy of this disease has increased. Due to the declining protective capacity of vaccines against new strains, as well as increased knowledge about the structure and biology of the pathogen, control of the disease has shifted to the focus of antiviral drug development over the past year. Clinical data on safety and efficacy of antivirals acting at various stages of the virus life cycle has been published. In this review, we summarize mechanisms and clinical efficacy of antiviral therapy of COVID-19 with drugs based on plasma of convalescents, monoclonal antibodies, interferons, fusion inhibitors, nucleoside analogs, and protease inhibitors. The current status of the drugs described is also summarized in relation to the official clinical guidelines for the treatment of COVID-19. In addition, here we describe innovative drugs whose antiviral effect is provided by antisense oligonucleotides targeting the SARS-CoV-2 genome. Analysis of laboratory and clinical data suggests that current antivirals successfully combat broad spectra of emerging strains of SARS-CoV-2 providing reliable defense against COVID-19.
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Meade, Elaine, Neil Rowan, and Mary Garvey. "Bioprocessing and the Production of Antiviral Biologics in the Prevention and Treatment of Viral Infectious Disease." Vaccines 11, no. 5 (May 17, 2023): 992. http://dx.doi.org/10.3390/vaccines11050992.
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Emerging, re-emerging and zoonotic viral pathogens represent a serious threat to human health, resulting in morbidity, mortality and potentially economic instability at a global scale. Certainly, the recent emergence of the novel SARS-CoV-2 virus (and its variants) highlighted the impact of such pathogens, with the pandemic creating unprecedented and continued demands for the accelerated production of antiviral therapeutics. With limited effective small molecule therapies available for metaphylaxis, vaccination programs have been the mainstay against virulent viral species. Traditional vaccines remain highly effective at providing high antibody titres, but are, however, slow to manufacture in times of emergency. The limitations of traditional vaccine modalities may be overcome by novel strategies, as outlined herein. To prevent future disease outbreaks, paradigm shift changes in manufacturing and distribution are necessary to advance the production of vaccines, monoclonal antibodies, cytokines and other antiviral therapies. Accelerated paths for antivirals have been made possible due to advances in bioprocessing, leading to the production of novel antiviral agents. This review outlines the role of bioprocessing in the production of biologics and advances in mitigating viral infectious disease. In an era of emerging viral diseases and the proliferation of antimicrobial resistance, this review provides insight into a significant method of antiviral agent production which is key to protecting public health.
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Venkataraman, Srividhya. "Plant Molecular Pharming and Plant-Derived Compounds towards Generation of Vaccines and Therapeutics against Coronaviruses." Vaccines 10, no. 11 (October 26, 2022): 1805. http://dx.doi.org/10.3390/vaccines10111805.
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The current century has witnessed infections of pandemic proportions caused by Coronaviruses (CoV) including severe acute respiratory syndrome-related CoV (SARS-CoV), Middle East respiratory syndrome-related CoV (MERS-CoV) and the recently identified SARS-CoV2. Significantly, the SARS-CoV2 outbreak, declared a pandemic in early 2020, has wreaked devastation and imposed intense pressure on medical establishments world-wide in a short time period by spreading at a rapid pace, resulting in high morbidity and mortality. Therefore, there is a compelling need to combat and contain the CoV infections. The current review addresses the unique features of the molecular virology of major Coronaviruses that may be tractable towards antiviral targeting and design of novel preventative and therapeutic intervention strategies. Plant-derived vaccines, in particular oral vaccines, afford safer, effectual and low-cost avenues to develop antivirals and fast response vaccines, requiring minimal infrastructure and trained personnel for vaccine administration in developing countries. This review article discusses recent developments in the generation of plant-based vaccines, therapeutic/drug molecules, monoclonal antibodies and phytochemicals to preclude and combat infections caused by SARS-CoV, MERS-CoV and SARS-CoV-2 viruses. Efficacious plant-derived antivirals could contribute significantly to combating emerging and re-emerging pathogenic CoV infections and help stem the tide of any future pandemics.
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Lundstrom, Kenneth. "Coronavirus Pandemic—Therapy and Vaccines." Biomedicines 8, no. 5 (May 3, 2020): 109. http://dx.doi.org/10.3390/biomedicines8050109.
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The current coronavirus COVID-19 pandemic, which originated in Wuhan, China, has raised significant social, psychological and economic concerns in addition to direct medical issues. The rapid spread of severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 to almost every country on the globe and the failure to contain the infections have contributed to fear and panic worldwide. The lack of available and efficient antiviral drugs or vaccines has further worsened the situation. For these reasons, it cannot be overstated that an accelerated effort for the development of novel drugs and vaccines is needed. In this context, novel approaches in both gene therapy and vaccine development are essential. Previous experience from SARS- and MERS-coronavirus vaccine and drug development projects have targeted glycoprotein epitopes, monoclonal antibodies, angiotensin receptor blockers and gene silencing technologies, which may be useful for COVID-19 too. Moreover, existing antivirals used for other types of viral infections have been considered as urgent action is necessary. This review aims at providing a background of coronavirus genetics and biology, examples of therapeutic and vaccine strategies taken and potential innovative novel approaches in progress.
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Ho, Ting-Hin, Chun Kew, Pak-Yin Lui, Chi-Ping Chan, Takashi Satoh, Shizuo Akira, Dong-Yan Jin, and Kin-Hang Kok. "PACT- and RIG-I-Dependent Activation of Type I Interferon Production by a Defective Interfering RNA Derived from Measles Virus Vaccine." Journal of Virology 90, no. 3 (November 25, 2015): 1557–68. http://dx.doi.org/10.1128/jvi.02161-15.
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ABSTRACTThe live attenuated measles virus vaccine is highly immunostimulatory. Identification and characterization of its components that activate the innate immune response might provide new strategies and agents for the rational design and development of chemically defined adjuvants. In this study, we report on the activation of type I interferon (IFN) production by a defective interfering (DI) RNA isolated from the Hu-191 vaccine strain of measles virus. We found that the Hu-191 virus induced IFN-β much more potently than the Edmonston strain. In the search for IFN-inducing species in Hu-191, we identified a DI RNA specifically expressed by this strain. This DI RNA, which was of the copy-back type, was predicted to fold into a hairpin structure with a long double-stranded stem region of 206 bp, and it potently induced the expression of IFN-β. Its IFN-β-inducing activity was further enhanced when both cytoplasmic RNA sensor RIG-I and its partner, PACT, were overexpressed. On the contrary, this activity was abrogated in cells deficient in PACT or RIG-I. The DI RNA was found to be associated with PACT in infected cells. In addition, both the 5′-di/triphosphate end and the double-stranded stem region on the DI RNA were essential for its activation of PACT and RIG-I. Taken together, our findings support a model in which a viral DI RNA is sensed by PACT and RIG-I to initiate an innate antiviral response. Our work might also provide a foundation for identifying physiological PACT ligands and developing novel adjuvants or antivirals.IMPORTANCEThe live attenuated measles virus vaccine is one of the most successful human vaccines and has largely contained the devastating impact of a highly contagious virus. Identifying the components in this vaccine that stimulate the host immune response and understanding their mechanism of action might help to design and develop better adjuvants, vaccines, antivirals, and immunotherapeutic agents. We identified and characterized a defective interfering RNA from the Hu-191 vaccine strain of measles virus which has safely been used in millions of people for many years. We further demonstrated that this RNA potently induces an antiviral immune response through cellular sensors of viral RNA known as PACT and RIG-I. Similar types of viral RNA that bind with and activate PACT and RIG-I might retain the immunostimulatory property of measles virus vaccines but would not induce adaptive immunity. They are potentially useful as chemically defined vaccine adjuvants, antivirals, and immunostimulatory agents.
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Oberemok, Volodymyr V., Oksana A. Andreeva, and Edie E. Alieva. "DNA Oligonucleotides as Antivirals and Vaccine Constituents against SARS Coronaviruses: A Prospective Tool for Immune System Tuning." International Journal of Molecular Sciences 24, no. 2 (January 13, 2023): 1553. http://dx.doi.org/10.3390/ijms24021553.
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The SARS-CoV-2 pandemic has demonstrated the need to create highly effective antivirals and vaccines against various RNA viruses, including SARS coronaviruses. This paper provides a short review of innovative strategies in the development of antivirals and vaccines against SARS coronaviruses, with a focus on antisense antivirals, oligonucleotide adjuvants in vaccines, and oligonucleotide vaccines. Well-developed viral genomic databases create new opportunities for the development of innovative vaccines and antivirals using a post-genomic platform. The most effective vaccines against SARS coronaviruses are those able to form highly effective memory cells for both humoral and cellular immunity. The most effective antivirals need to efficiently stop viral replication without side effects. Oligonucleotide antivirals and vaccines can resist the rapidly changing genomic sequences of SARS coronaviruses using conserved regions of their genomes to generate a long-term immune response. Oligonucleotides have been used as excellent adjuvants for decades, and increasing data show that oligonucleotides could serve as antisense antivirals and antigens in vaccine formulations, becoming a prospective tool for immune system tuning.
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Lin, Pin-Hung, and Hung-Chih Yang. "Suppression of vaccination-induced antigen-specific regulatory T cells enhances the antiviral immunity against influenza virus infection." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 199.9. http://dx.doi.org/10.4049/jimmunol.198.supp.199.9.
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Abstract T cell immunity targeting the conserved epitopes of influenza virus has the potential to provide cross-protection against distinctly-related strains. Peptide vaccines are an ideal strategy to induce specific antiviral T cell immunity, but subimmunogenic stimulation by peptide vaccines tend to induce regulatory T (Treg) cells. However, it remains unclear about the roles of vaccine-induced antigen-specific Treg cells in vivo. Here, we aimed to investigate how vaccine-induced antigen-specific Treg cells respond during acute influenza virus infection, and the effects of adjuvants on them. By adoptive transfer experiments with OT-II TCR transgenic T cells, we found that the OVA OT-II peptide vaccine induced Treg cells and secondary vaccination further expanded them. Infection with influenza virus containing the OVA OT-II peptide also drove the expansion of pre-existing vaccine-induced Treg cells. Importantly, specific depletion of vaccine-induced antigen-specific Treg cells enhanced the antiviral immunity. Vaccination combined with adjuvants, especially with CpG, suppressed the development of vaccine-induced antigen-specific Treg cells. Finally, CpG-adjuvanted OVA protein or whole inactivated influenza vaccine by the subcutaneous-prime-intranasal-boost strategy reduced the ratio of antigen-specific Treg cells in lung and protected mice from the heterosubtypic influenza infection. In conclusion, unadjuvanted peptide vaccines promoted antigen-specific Treg cells, which were further expanded upon acute influenza infection. The CpG adjuvant restricted the development of vaccine-induced antigen-specific Treg cells, and enhanced the antiviral T cell immunity against heterosubtypic influenza infection.
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Rand, Ulfert, Sascha Young Kupke, Hanna Shkarlet, Marc Dominique Hein, Tatjana Hirsch, Pavel Marichal-Gallardo, Luka Cicin-Sain, Udo Reichl, and Dunja Bruder. "Antiviral Activity of Influenza A Virus Defective Interfering Particles against SARS-CoV-2 Replication In Vitro through Stimulation of Innate Immunity." Cells 10, no. 7 (July 11, 2021): 1756. http://dx.doi.org/10.3390/cells10071756.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) emerged in late 2019 and resulted in a devastating pandemic. Although the first approved vaccines were already administered by the end of 2020, worldwide vaccine availability is still limited. Moreover, immune escape variants of the virus are emerging against which the current vaccines may confer only limited protection. Further, existing antivirals and treatment options against COVID-19 show only limited efficacy. Influenza A virus (IAV) defective interfering particles (DIPs) were previously proposed not only for antiviral treatment of the influenza disease but also for pan-specific treatment of interferon (IFN)-sensitive respiratory virus infections. To investigate the applicability of IAV DIPs as an antiviral for the treatment of COVID-19, we conducted in vitro co-infection experiments with cell culture-derived DIPs and the IFN-sensitive SARS-CoV-2 in human lung cells. We show that treatment with IAV DIPs leads to complete abrogation of SARS-CoV-2 replication. Moreover, this inhibitory effect was dependent on janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling. Further, our results suggest boosting of IFN-induced antiviral activity by IAV DIPs as a major contributor in suppressing SARS-CoV-2 replication. Thus, we propose IAV DIPs as an effective antiviral agent for treatment of COVID-19, and potentially also for suppressing the replication of new variants of SARS-CoV-2.
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Geraghty, Robert, Matthew Aliota, and Laurent Bonnac. "Broad-Spectrum Antiviral Strategies and Nucleoside Analogues." Viruses 13, no. 4 (April 13, 2021): 667. http://dx.doi.org/10.3390/v13040667.
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The emergence or re-emergence of viruses with epidemic and/or pandemic potential, such as Ebola, Zika, Middle East Respiratory Syndrome (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus 1 and 2 (SARS and SARS-CoV-2) viruses, or new strains of influenza represents significant human health threats due to the absence of available treatments. Vaccines represent a key answer to control these viruses. However, in the case of a public health emergency, vaccine development, safety, and partial efficacy concerns may hinder their prompt deployment. Thus, developing broad-spectrum antiviral molecules for a fast response is essential to face an outbreak crisis as well as for bioweapon countermeasures. So far, broad-spectrum antivirals include two main categories: the family of drugs targeting the host-cell machinery essential for virus infection and replication, and the family of drugs directly targeting viruses. Among the molecules directly targeting viruses, nucleoside analogues form an essential class of broad-spectrum antiviral drugs. In this review, we will discuss the interest for broad-spectrum antiviral strategies and their limitations, with an emphasis on virus-targeted, broad-spectrum, antiviral nucleoside analogues and their mechanisms of action.
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Hosie, Margaret J., Thomas Dunsford, Dieter Klein, Brian J. Willett, Celia Cannon, Robert Osborne, Julie MacDonald, et al. "Vaccination with Inactivated Virus but Not Viral DNA Reduces Virus Load following Challenge with a Heterologous and Virulent Isolate of Feline Immunodeficiency Virus." Journal of Virology 74, no. 20 (October 15, 2000): 9403–11. http://dx.doi.org/10.1128/jvi.74.20.9403-9411.2000.
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ABSTRACT It has been shown that cats can be protected against infection with the prototypic Petaluma strain of feline immunodeficiency virus (FIVPET) using vaccines based on either inactivated virus particles or replication-defective proviral DNA. However, the utility of such vaccines in the field is uncertain, given the absence of consistent protection against antigenically distinct strains and the concern that the Petaluma strain may be an unrepresentative, attenuated isolate. Since reduction of viral pathogenicity and dissemination may be useful outcomes of vaccination, even in the absence of complete protection, we tested whether either of these vaccine strategies ameliorates the early course of infection following challenge with heterologous and more virulent isolates. We now report that an inactivated virus vaccine, which generates high levels of virus neutralizing antibodies, confers reduced virus loads following challenge with two heterologous isolates, FIVAM6 and FIVGL8. This vaccine also prevented the marked early decline in CD4/CD8 ratio seen in FIVGL8-infected cats. In contrast, DNA vaccines based on either FIVPET or FIVGL8, which induce cell-mediated responses but no detectable antiviral antibodies, protected a fraction of cats against infection with FIVPET but had no measurable effect on virus load when the infecting virus was FIVGL8. These results indicate that the more virulent FIVGL8 is intrinsically more resistant to vaccinal immunity than the FIVPET strain and that a broad spectrum of responses which includes virus neutralizing antibodies is a desirable goal for lentivirus vaccine development.
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Pollara, Justin, Mattia Bonsignori, M. Anthony Moody, Pinghuang Liu, S. Munir Alam, Kwan-Ki Hwang, Thaddeus C. Gurley, et al. "HIV-1 Vaccine-Induced C1 and V2 Env-Specific Antibodies Synergize for Increased Antiviral Activities." Journal of Virology 88, no. 14 (May 7, 2014): 7715–26. http://dx.doi.org/10.1128/jvi.00156-14.
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ABSTRACTThe RV144 ALVAC/AIDSVax HIV-1 vaccine clinical trial showed an estimated vaccine efficacy of 31.2%. Viral genetic analysis identified a vaccine-induced site of immune pressure in the HIV-1 envelope (Env) variable region 2 (V2) focused on residue 169, which is included in the epitope recognized by vaccinee-derived V2 monoclonal antibodies. The ALVAC/AIDSVax vaccine induced antibody-dependent cellular cytotoxicity (ADCC) against the Env V2 and constant 1 (C1) regions. In the presence of low IgA Env antibody levels, plasma levels of ADCC activity correlated with lower risk of infection. In this study, we demonstrate that C1 and V2 monoclonal antibodies isolated from RV144 vaccinees synergized for neutralization, infectious virus capture, and ADCC. Importantly, synergy increased the HIV-1 ADCC activity of V2 monoclonal antibody CH58 at concentrations similar to that observed in plasma of RV144 vaccinees. These findings raise the hypothesis that synergy among vaccine-induced antibodies with different epitope specificities contributes to HIV-1 antiviral antibody responses and is important to induce for reduction in the risk of HIV-1 transmission.IMPORTANCEThe Thai RV144 ALVAC/AIDSVax prime-boost vaccine efficacy trial represents the only example of HIV-1 vaccine efficacy in humans to date. Studies aimed at identifying immune correlates involved in the modest vaccine-mediated protection identified HIV-1 envelope (Env) variable region 2-binding antibodies as inversely correlated with infection risk, and genetic analysis identified a site of immune pressure within the region recognized by these antibodies. Despite this evidence, the antiviral mechanisms by which variable region 2-specific antibodies may have contributed to lower rates of infection remain unclear. In this study, we demonstrate that vaccine-induced HIV-1 envelope variable region 2 and constant region 1 antibodies synergize for recognition of virus-infected cells, infectious virion capture, virus neutralization, and antibody-dependent cellular cytotoxicity. This is a major step in understanding how these types of antibodies may have cooperatively contributed to reducing infection risk and should be considered in the context of prospective vaccine design.
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Santos-Mendoza, Teresa. "The Envelope (E) Protein of SARS-CoV-2 as a Pharmacological Target." Viruses 15, no. 4 (April 19, 2023): 1000. http://dx.doi.org/10.3390/v15041000.
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The COVID-19 pandemic caused by the SARS-CoV-2 virus is still a global health concern. Several spike (S) protein-based vaccines have been developed that efficiently protect the human population against severe forms of COVID-19. However, some SARS-CoV-2 variants of concern (VOCs) have emerged that evade the protective effect of vaccine-induced antibodies. Therefore, efficient and specific antiviral treatments to control COVID-19 are indispensable. To date, two drugs have been approved for mild COVID-19 treatment; nevertheless, more drugs, preferably broad-spectrum and ready-to-use therapeutic agents for new pandemics, are needed. Here, I discuss the PDZ-dependent protein-protein interactions of the viral E protein with host proteins as attractive alternatives for the development of antivirals against coronavirus.
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Bormann, Maren, Lukas van de Sand, Oliver Witzke, and Adalbert Krawczyk. "Recent Antiviral Treatment and Vaccination Strategies Against SARS-CoV-2." Klinische Monatsblätter für Augenheilkunde 238, no. 05 (May 2021): 569–78. http://dx.doi.org/10.1055/a-1423-8961.
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AbstractSince the end of 2019, the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has been spreading worldwide and has caused severe health and economic issues on a global scale. By the end of February 2021, more than 100 million SARS-CoV-2 cases had been reported worldwide. SARS-CoV-2 causes the coronavirus disease 2019 (COVID-19) that can be divided into three phases: An early phase with fever and cough (phase I), a pulmonary vascular disease (phase II) and a hyperinflammatory syndrome (phase III). Since viral replication plays a particularly important role in the early stage of the disease and the patientʼs immune system in the later course of infection, different therapeutic options arise depending on the stage of the disease. The antiviral nucleoside analogue remdesivir is the only antiviral compound with conditional approval in the European Union. Treatment with remdesivir should be initiated early (within the first seven days of symptom onset) in patients receiving supplemental oxygen without invasive ventilation. In turn, the anti-inflammatory corticosteroid dexamethasone should be administered later in the course of disease in patients receiving oxygen therapy. Since autopsies indicate an increased frequency of thromboembolic events due to COVID-19, additional treatment with anticoagulants is recommended. Since the development of novel antivirals may take years, the application of convalescent plasma from patients who recovered from a SARS-CoV-2 infection for the treatment of COVID-19 is reasonable. However, large-scale studies indicated low efficacy of convalescent plasma. Furthermore, vaccination of the population is essential to control the pandemic. Currently, the mRNA vaccine Tozinameran from BioNTech and Pfizer, the mRNA-1273 vaccine from Moderna as well as the vector vaccine AZD1222 from AstraZeneca are licensed in the European Union. All three vaccines have demonstrated high efficacy in large clinical trials. In addition to these licensed vaccines, many others are being tested in clinical trials. In the present article, an overview of therapeutic options for COVID-19 as well as vaccines for protection against SARS-CoV-2 is provided.
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Heena Bholaram Choudhary, Indra Hemaram Sirvi, Yash Rajendra Bamb, Priyanka Rajendra Bamb, and Rohan RajkumarPatekar. "COVID-19 Vaccines: Systematic review." World Journal of Advanced Research and Reviews 10, no. 1 (April 30, 2021): 143–55. http://dx.doi.org/10.30574/wjarr.2021.10.1.0118.
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World facing pandemic challenges of SARS-Co-2 (Severe Acute Respiratory Syndrome Corona Virus 2). Tyrrell and Bynoe identified first strain of human corona virus in 1965. Infection was originated from Wuhan city of China on November 2019. Virus officially named as COVID-19 which causes respiratory tract infections in humans. Preliminary symptoms like chest pain with difficulty in breathing, reduced in systemic oxygen level, cough and fever. At present, the majority of the pharmaceutical companies were in race to developing antiviral drug and vaccines against COVID-19. Industries conducting the experiment and clinical trial of various vaccines to ensure effectiveness and safety on human. Several of them were documentation for patent, authorization of clinical trial and marketing. We provide an overview of Covid-19 history, types of vaccine and mechanism of actions, current future therapeutic drugs and patents. Relative with the mechanism of actions such as inactivated vaccine, vector vaccines, DNA and RNA based vaccine and antiviral drugs already entered in (Phase II and III) clinical trials. The systemic study specified brief summary of various vaccines. Current status of clinical trial, safety and effectiveness according to ICH guidelines. A major adverse interaction with their toxicity study. The information of approved which give opportunity for upcoming scientist to improve the quality, and minimize the adverse effects. Scientist may face challenges during the post marketing clinical trial. This pandemic has provided various scopes for researchers to develop vaccine and antiviral drugs.
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Cuburu, Nicolas, Shiv Sethi, Lukasz Bialkowski, Cynthia Thompson, Sergio M. Pontejo, and John T. Schiller. "Antiviral vaccines for local immunotherapy against solid tumors." Journal of Immunology 210, no. 1_Supplement (May 1, 2023): 68.14. http://dx.doi.org/10.4049/jimmunol.210.supp.68.14.
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Abstract Local immunotherapy against solid tumors is considered a viable approach to stimulate the tumor immune microenvironment and anti-tumor immunity. Here, we interrogate whether preexisting anti-vaccine immunity induced by licensed subunit vaccines could be leveraged for local cancer immunotherapy in the syngeneic murine tumor models. We selected Shingrix, a VZV vaccine containing the glycoprotein E (gE) antigen and adjuvant AS01B, and Gardasil-9, a HPV vaccine containing the L1 virus-like particles and alum because of the CD4 and CD8 T cell responses they respectively induce. Intratumoral injection of Shingrix alone or with immune checkpoint blockade (CTLA-4), in prevaccinated mice delayed tumor growth and often led to complete regression. These responses were associated with the induction of CD8+ T cell responses against tumor associated antigen, to tumor immune activation and alteration of the myeloid compartment. The injection of selected MHC-II-restricted gE minimal peptide epitopes combined with polyI:C also led to durable remission suggesting a contribution of gE-specific CD4 T cells. In contrast, Gardasil-9 i.t. injection did not delay tumor growth or cause tumor rejection which suggests inefficient class I cross-presentation of native VLP in the tumor cells. However, the injection of MHC-I-restricted L1 minimal peptide epitopes led to complete and durable remissions suggesting efficient tumor control by L1-specific CD8 T cells. Our results suggest that anti-viral licensed vaccines can be leverage as a new class of immunotherapeutics for local cancer therapy and intrinsic immunogenicity properties of vaccines should be considered as these effects appeared to be vaccine specific. NIH Intramural program.
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Malik, Shiza, Omar Ahsan, Hassan Mumtaz, Muhammad Tahir Khan, Ranjit Sah, and Yasir Waheed. "Tracing down the Updates on Dengue Virus—Molecular Biology, Antivirals, and Vaccine Strategies." Vaccines 11, no. 8 (August 5, 2023): 1328. http://dx.doi.org/10.3390/vaccines11081328.
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Background: Nearly half of the world is at risk of developing dengue infection. Dengue virus is the causative agent behind this public healthcare concern. Millions of dengue cases are reported every year, leading to thousands of deaths. The scientific community is working to develop effective therapeutic strategies in the form of vaccines and antiviral drugs against dengue. Methods: In this review, a methodological approach has been used to gather data from the past five years to include the latest developments against the dengue virus. Results: Different therapeutics and antiviral targets against the dengue virus are at different stages of development, but none have been approved by the FDA. Moreover, various vaccination strategies have also been discussed, including attenuated virus vaccines, recombinant subunit vaccines, viral vector vaccines, DNA vaccines, nanotechnology, and plant-based vaccines, which are used to develop effective vaccines for the dengue virus. Many dengue vaccines pass the initial phases of evaluation, but only two vaccines have been approved for public use. DENGVAXIA is the only FDA-approved vaccine against all four stereotypes of the dengue virus, but it is licensed for use only in individuals 6–16 years of age with laboratory-confirmed previous dengue infection and living in endemic countries. Takeda is the second vaccine approved for use in the European Union, the United Kingdom, Brazil, Argentina, Indonesia, and Thailand. It produced sustained antibody responses against all four serotypes of dengue virus, regardless of previous exposure and dosing schedule. Other dengue vaccine candidates at different stages of development are TV-003/005, TDENV PIV, V180, and some DNA vaccines. Conclusion: There is a need to put more effort into developing effective vaccines and therapeutics for dengue, as already approved vaccines and therapeutics have limitations. DENGVAXIA is approved for use in children and teenagers who are 6–16 years of age and have confirmed dengue infection, while Takeda is approved for use in certain countries, and it has withdrawn its application for FDA approval.
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Schlotthauer, Felicia, Joey McGregor, and Heidi E. Drummer. "To Include or Occlude: Rational Engineering of HCV Vaccines for Humoral Immunity." Viruses 13, no. 5 (April 30, 2021): 805. http://dx.doi.org/10.3390/v13050805.
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Direct-acting antiviral agents have proven highly effective at treating existing hepatitis C infections but despite their availability most countries will not reach the World Health Organization targets for elimination of HCV by 2030. A prophylactic vaccine remains a high priority. Whilst early vaccines focused largely on generating T cell immunity, attention is now aimed at vaccines that generate humoral immunity, either alone or in combination with T cell-based vaccines. High-resolution structures of hepatitis C viral glycoproteins and their interaction with monoclonal antibodies isolated from both cleared and chronically infected people, together with advances in vaccine technologies, provide new avenues for vaccine development.
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Lu, Chenxing, Yan Li, Rong Chen, Xiaoqing Hu, Qingmei Leng, Xiaopeng Song, Xiaochen Lin, et al. "Safety, Immunogenicity, and Mechanism of a Rotavirus mRNA-LNP Vaccine in Mice." Viruses 16, no. 2 (January 31, 2024): 211. http://dx.doi.org/10.3390/v16020211.
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Rotaviruses (RVs) are a major cause of diarrhea in young children worldwide. The currently available and licensed vaccines contain live attenuated RVs. Optimization of live attenuated RV vaccines or developing non-replicating RV (e.g., mRNA) vaccines is crucial for reducing the morbidity and mortality from RV infections. Herein, a nucleoside-modified mRNA vaccine encapsulated in lipid nanoparticles (LNP) and encoding the VP7 protein from the G1 type of RV was developed. The 5′ untranslated region of an isolated human RV was utilized for the mRNA vaccine. After undergoing quality inspection, the VP7-mRNA vaccine was injected by subcutaneous or intramuscular routes into mice. Mice received three injections in 21 d intervals. IgG antibodies, neutralizing antibodies, cellular immunity, and gene expression from peripheral blood mononuclear cells were evaluated. Significant differences in levels of IgG antibodies were not observed in groups with adjuvant but were observed in groups without adjuvant. The vaccine without adjuvant induced the highest antibody titers after intramuscular injection. The vaccine elicited a potent antiviral immune response characterized by antiviral clusters of differentiation CD8+ T cells. VP7-mRNA induced interferon-γ secretion to mediate cellular immune responses. Chemokine-mediated signaling pathways and immune response were activated by VP7-mRNA vaccine injection. The mRNA LNP vaccine will require testing for protective efficacy, and it is an option for preventing rotavirus infection.
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Whitley, Richard, and Joel Baines. "Clinical management of herpes simplex virus infections: past, present, and future." F1000Research 7 (October 31, 2018): 1726. http://dx.doi.org/10.12688/f1000research.16157.1.
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Infection with herpes simplex virus (HSV) types 1 and 2 is ubiquitous in the human population. Most commonly, virus replication is limited to the epithelia and establishes latency in enervating sensory neurons, reactivating periodically to produce localized recurrent lesions. However, these viruses can also cause severe disease such as recurrent keratitis leading potentially to blindness, as well as encephalitis, and systemic disease in neonates and immunocompromised patients. Although antiviral therapy has allowed continual and substantial improvement in the management of both primary and recurrent infections, resistance to currently available drugs and long-term toxicity pose a current and future threat that should be addressed through the development of new antiviral compounds directed against new targets. The development of several promising HSV vaccines has been terminated recently because of modest or controversial therapeutic effects in humans. Nevertheless, several exciting vaccine candidates remain in the pipeline and are effective in animal models; these must also be tested in humans for sufficient therapeutic effects to warrant continued development. Approaches using compounds that modulate the chromatin state of the viral genome to suppress infection and reactivation or induce enhanced antiviral immunity have potential. In addition, technologies such as CRISPR/Cas9 have the potential to edit latent viral DNA in sensory neurons, potentially curing the neuron and patient of latent infection. It is hoped that development on all three fronts—antivirals, vaccines, and gene editing—will lead to substantially less HSV morbidity in the future.
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O'Brien, Lyn, Stuart Perkins, Amanda Williams, Lin Eastaugh, Amanda Phelps, Josh Wu, and Robert Phillpotts. "Alpha interferon as an adenovirus-vectored vaccine adjuvant and antiviral in Venezuelan equine encephalitis virus infection." Journal of General Virology 90, no. 4 (April 1, 2009): 874–82. http://dx.doi.org/10.1099/vir.0.006833-0.
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There are no widely available vaccines or antiviral drugs capable of protecting against infection with Venezuelan equine encephalitis virus (VEEV), although an adenovirus vector expressing VEEV structural proteins protects mice from challenge with VEEV and is potentially a vaccine suitable for human use. This work examines whether alpha interferon (IFN-α) could act as an adjuvant for the adenovirus-based vaccine. IFN-α was either expressed by a plasmid linked to the adenovirus vaccine or encoded by a separate adenovirus vector administered as a mixture with the vaccine. In contrast to previous reports with other vaccines, the presence of IFN-α reduced the antibody response to VEEV. When IFN-α was encoded by adenovirus, the lack of a VEEV-specific response was accompanied by an increase in the immune response to the adenovirus vector. IFN-α also plays a direct role in defence against virus infection, inducing the expression of a large number of antiviral proteins. Adenovirus-delivered IFN-α protected mice from VEEV disease when administered 24 h prior to challenge, but not when administered 6 h post-challenge, suggesting that up to 24 h is required for the development of the IFN-mediated antiviral response.
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Coultas, James Andrew, Rosalind Smyth, and Peter J. Openshaw. "Respiratory syncytial virus (RSV): a scourge from infancy to old age." Thorax 74, no. 10 (August 5, 2019): 986–93. http://dx.doi.org/10.1136/thoraxjnl-2018-212212.
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Respiratory syncytial virus (RSV) is the most common single cause of respiratory hospitalisation of infants and is the second largest cause of lower respiratory infection mortality worldwide. In adults, RSV is an under-recognised cause of deterioration in health, particularly in frail elderly persons. Infection rates typically rise in late autumn and early winter causing bronchiolitis in infants, common colds in adults and insidious respiratory illness in the elderly. Virus detection methods optimised for use in children have low detection rate in adults, highlighting the need for better diagnostic tests. There are many vaccines under development, mostly based on the surface glycoprotein F which exists in two conformations (prefusion and postfusion). Much of the neutralising antibody appears to be to the prefusion form. Vaccines being developed include live attenuated, subunit, particle based and live vectored agents. Different vaccine strategies may be appropriate for different target populations: at-risk infants, school-age children, adult caregivers and the elderly. Antiviral drugs are in clinical trial and may find a place in disease management. RSV disease is one of the major remaining common tractable challenges in infectious diseases and the era of vaccines and antivirals for RSV is on the near horizon.
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Ali, Muhammad Zahid, Yousra Anwar, Adil Abbas, Noor Ul Ain, Zainab Khalid, Arooj Sattar, Muhammad Usman, Arzoo Nazir, and Shah Zeb. "Recent Advances in Vaccine Technology for Viral Infection Management: A Spotlight on Next-Generation Vaccines and Nucleic Acid-Based Platforms." Pakistan Journal of Medical and Health Sciences 17, no. 5 (June 23, 2023): 261–66. http://dx.doi.org/10.53350/pjmhs2023175261.
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Recent advances in vaccine technology and their uses in viral infection management were the focus of the study. Potential nucleic acid-based platforms for vaccine development, including DNA and RNA vaccines, were also investigated. During the COVID-19 pandemic, a lot of attention was paid to RNA-based vaccinations like mRNA vaccines because of their rapid development and scalability. These vaccines were shown to be effective at eliciting protective immune responses and provided the adaptability to include multiple antigenic sites. Preclinical and clinical research of this magnitude is required for the development and assessment of these innovative vaccine methods. Immunogenicity, side effects, and efficacy were all taken into account. The study highlighted the need for more investigation and cooperation between researchers, physicians, and business allies to speed up the process of turning these novel vaccine strategies into successful therapies against different types of viral infections. Our study demonstrated the potential of viral vectors, nanoparticles, and nucleic acid-based platforms in developing vaccine technology, and it contributes important insights into the design and evaluation of innovative vaccine tactics against viral diseases. These results add to the existing body of knowledge and may help direct future antiviral research and development. Keywords: Vaccine development, Viruses, DNA Vaccines, RNA Vaccines, COVID-19 Vaccines
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Ng, Teresa I., Ivan Correia, Jane Seagal, David A. DeGoey, Michael R. Schrimpf, David J. Hardee, Elizabeth L. Noey, and Warren M. Kati. "Antiviral Drug Discovery for the Treatment of COVID-19 Infections." Viruses 14, no. 5 (May 4, 2022): 961. http://dx.doi.org/10.3390/v14050961.
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The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recently emerged human coronavirus. COVID-19 vaccines have proven to be successful in protecting the vaccinated from infection, reducing the severity of disease, and deterring the transmission of infection. However, COVID-19 vaccination faces many challenges, such as the decline in vaccine-induced immunity over time, and the decrease in potency against some SARS-CoV-2 variants including the recently emerged Omicron variant, resulting in breakthrough infections. The challenges that COVID-19 vaccination is facing highlight the importance of the discovery of antivirals to serve as another means to tackle the pandemic. To date, neutralizing antibodies that block viral entry by targeting the viral spike protein make up the largest class of antivirals that has received US FDA emergency use authorization (EUA) for COVID-19 treatment. In addition to the spike protein, other key targets for the discovery of direct-acting antivirals include viral enzymes that are essential for SARS-CoV-2 replication, such as RNA-dependent RNA polymerase and proteases, as judged by US FDA approval for remdesivir, and EUA for Paxlovid (nirmatrelvir + ritonavir) for treating COVID-19 infections. This review presents an overview of the current status and future direction of antiviral drug discovery for treating SARS-CoV-2 infections, covering important antiviral targets such as the viral spike protein, non-structural protein (nsp) 3 papain-like protease, nsp5 main protease, and the nsp12/nsp7/nsp8 RNA-dependent RNA polymerase complex.
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Uribe-Sánchez, Andrés, and Alex Savachkin. "Predictive and Reactive Distribution of Vaccines and Antivirals during Cross-Regional Pandemic Outbreaks." Influenza Research and Treatment 2011 (June 5, 2011): 1–14. http://dx.doi.org/10.1155/2011/579597.
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As recently pointed out by the Institute of Medicine, the existing pandemic mitigation models lack the dynamic decision support capability. We develop a large-scale simulation-driven optimization model for generating dynamic predictive distribution of vaccines and antivirals over a network of regional pandemic outbreaks. The model incorporates measures of morbidity, mortality, and social distancing, translated into the cost of lost productivity and medical expenses. The performance of the strategy is compared to that of the reactive myopic policy, using a sample outbreak in Fla, USA, with an affected population of over four millions. The comparison is implemented at different levels of vaccine and antiviral availability and administration capacity. Sensitivity analysis is performed to assess the impact of variability of some critical factors on policy performance. The model is intended to support public health policy making for effective distribution of limited mitigation resources.
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Noah, Diana L., and James W. Noah. "Adapting global influenza management strategies to address emerging viruses." American Journal of Physiology-Lung Cellular and Molecular Physiology 305, no. 2 (July 15, 2013): L108—L117. http://dx.doi.org/10.1152/ajplung.00105.2013.
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Death by respiratory complications from influenza infections continues to be a major global health concern. Antiviral drugs are widely available for therapy and prophylaxis, but viral mutations have resulted in resistance that threatens to reduce the long-term utility of approved antivirals. Vaccination is the best method for controlling influenza, but vaccine strategies are blunted by virus antigenic drift and shift. Genetic shift in particular has led to four pandemics in the last century, which have prompted the development of efficient global surveillance and vaccination programs. Although the influenza pandemic of 2009 emphasized the need for the rapid standardization of global surveillance methods and the preparation and dissemination of global assay standards for improved reporting and diagnostic tools, outbreaks of novel influenza strains continue to occur, and current efforts must be enhanced by aggressive public education programs to promote increased vaccination rates in the global population. Recently, a novel H7N9 avian influenza virus with potential to become a pandemic strain emerged in China and was transmitted from animals to humans with a demonstrated >20% mortality rate. Sporadic outbreaks of highly lethal avian virus strains have already increased public awareness and altered annual vaccine production strategies to prevent the natural adaption of this virus to human-to-human transmission. Additional strategies for combating influenza include advancement of new antivirals for unexploited viral or host cellular targets; novel adjuvants and alternate vaccine delivery systems; and development of universal protein, DNA, or multivalent vaccines designed to increase immune responsiveness and enhance public health response times.
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Lee, Michelle Felicia, Yuan Seng Wu, and Chit Laa Poh. "Molecular Mechanisms of Antiviral Agents against Dengue Virus." Viruses 15, no. 3 (March 8, 2023): 705. http://dx.doi.org/10.3390/v15030705.
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Dengue is a major global health threat causing 390 million dengue infections and 25,000 deaths annually. The lack of efficacy of the licensed Dengvaxia vaccine and the absence of a clinically approved antiviral against dengue virus (DENV) drive the urgent demand for the development of novel anti-DENV therapeutics. Various antiviral agents have been developed and investigated for their anti-DENV activities. This review discusses the mechanisms of action employed by various antiviral agents against DENV. The development of host-directed antivirals targeting host receptors and direct-acting antivirals targeting DENV structural and non-structural proteins are reviewed. In addition, the development of antivirals that target different stages during post-infection such as viral replication, viral maturation, and viral assembly are reviewed. Antiviral agents designed based on these molecular mechanisms of action could lead to the discovery and development of novel anti-DENV therapeutics for the treatment of dengue infections. Evaluations of combinations of antiviral drugs with different mechanisms of action could also lead to the development of synergistic drug combinations for the treatment of dengue at any stage of the infection.
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Zou, Yaru, Koju Kamoi, Yuan Zong, Jing Zhang, Mingming Yang, and Kyoko Ohno-Matsui. "Ocular Inflammation Post-Vaccination." Vaccines 11, no. 10 (October 23, 2023): 1626. http://dx.doi.org/10.3390/vaccines11101626.
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The association between vaccines and ocular disorders has attracted significant attention in scientific research. Numerous mainstream vaccines are associated with a range of uveitis types, including anterior, intermediate, and posterior uveitis. Additionally, they are associated with distinct ocular diseases such as multifocal choroiditis, Vogt–Koyanagi–Harada (VKH) disease, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and multiple evanescent white dot syndrome (MEWDS). These ocular conditions are often transient, with a vast majority of patients experiencing improvement after steroid intervention. To date, numerous cases of vaccine-induced uveitis have been reported. This study analyzed the correlation between antiviral vaccines, including the hepatitis B virus (HBV), human papillomavirus (HPV), measles–mumps–rubella (MMR), varicella zoster virus (VZV), and influenza vaccines, and different manifestations of uveitis. This is the first comprehensive study to offer a detailed analysis of uveitis types induced by antiviral vaccines. Through an extensive database search, we found a particularly strong link between influenza vaccines, followed by VZV and HPV vaccines. While anterior uveitis is common, conditions such as APMPPE, MEWDS, and VKH are particularly notable and merit careful consideration in clinical practice. Corticosteroid treatment was effective; however, half of the observed patients did not achieve full recovery, indicating potentially prolonged effects of the vaccine.
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Greener, Mark. "Influenza vaccines: an introduction." Practice Nursing 34, Sup1 (January 2, 2023): 10–16. http://dx.doi.org/10.12968/pnur.2023.34.sup1.s10.
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Seasonal influenza is a leading cause of severe respiratory infections and deaths. During an influenza infection, the immune system produces inflammatory mediators, which are largely responsible for the systemic symptoms and complications. Vaccines remain the most effective way to prevent influenza-related respiratory disease and non-respiratory complications despite antivirals. Numerous studies support the benefits of influenza vaccination, especially in high-risk groups. However, the effectiveness of the influenza vaccine varies markedly depending on the match between the circulating strains and those in the vaccine, and the recipient’s characteristics. Influenza vaccines are, in general, well-tolerated. Research could lead to more effective and, potentially, universal influenza vaccines.
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Gupta, Rajesh Kumar, Girish R. Apte, Kiran Bharat Lokhande, Satyendra Mishra, and Jayanta K. Pal. "Carbohydrate-Binding Agents: Potential of Repurposing for COVID-19 Therapy." Current Protein & Peptide Science 21, no. 11 (December 31, 2020): 1085–96. http://dx.doi.org/10.2174/1389203721666200918153717.
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: With the emergence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the whole world is suffering from atypical pneumonia, which resulted in more than 559,047 deaths worldwide. In this time of crisis and urgency, the only hope comes from new candidate vaccines and potential antivirals. However, formulating new vaccines and synthesizing new antivirals are a laborious task. Therefore, considering the high infection rate and mortality due to COVID-19, utilization of previous information, and repurposing of existing drugs against valid viral targets have emerged as a novel drug discovery approach in this challenging time. The transmembrane spike (S) glycoprotein of coronaviruses (CoVs), which facilitates the virus’s entry into the host cells, exists in a homotrimeric form and is covered with N-linked glycans. S glycoprotein is known as the main target of antibodies having neutralizing potency and is also considered as an attractive target for therapeutic or vaccine development. Similarly, targeting of N-linked glycans of S glycoprotein envelope of CoV via carbohydrate-binding agents (CBAs) could serve as an attractive therapeutic approach for developing novel antivirals. CBAs from natural sources like lectins from plants, marine algae and prokaryotes and lectin mimics like Pradimicin-A (PRM-A) have shown antiviral activities against CoV and other enveloped viruses. However, the potential use of CBAs specifically lectins was limited due to unfavorable responses like immunogenicity, mitogenicity, hemagglutination, inflammatory activity, cellular toxicity, etc. Here, we reviewed the current scenario of CBAs as antivirals against CoVs, presented strategies to improve the efficacy of CBAs against CoVs; and studied the molecular interactions between CBAs (lectins and PRM-A) with Man9 by molecular docking for potential repurposing against CoVs in general, and SARSCoV- 2, in particular.
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Nuño, M., G. Chowell, and A. B. Gumel. "Assessing the role of basic control measures, antivirals and vaccine in curtailing pandemic influenza: scenarios for the US, UK and the Netherlands." Journal of The Royal Society Interface 4, no. 14 (December 13, 2006): 505–21. http://dx.doi.org/10.1098/rsif.2006.0186.
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An increasing number of avian flu cases in humans, arising primarily from direct contact with poultry, in several regions of the world have prompted the urgency to develop pandemic preparedness plans worldwide. Leading recommendations in these plans include basic public health control measures for minimizing transmission in hospitals and communities, the use of antiviral drugs and vaccination. This paper presents a mathematical model for the evaluation of the pandemic flu preparedness plans of the United States (US), the United Kingdom (UK) and the Netherlands. The model is used to assess single and combined interventions. Using data from the US, we show that hospital and community transmission control measures alone can be highly effective in reducing the impact of a potential flu pandemic. We further show that while the use of antivirals alone could lead to very significant reductions in the burden of a pandemic, the combination of transmission control measures, antivirals and vaccine gives the most ‘optimal’ result. However, implementing such an optimal strategy at the onset of a pandemic may not be realistic. Thus, it is important to consider other plausible alternatives. An optimal preparedness plan is largely dependent on the availability of resources; hence, it is country-specific . We show that countries with limited antiviral stockpiles should emphasize their use therapeutically (rather than prophylactically). However, countries with large antiviral stockpiles can achieve greater reductions in disease burden by implementing them both prophylactically and therapeutically. This study promotes alternative strategies that may be feasible and attainable for the US, UK and the Netherlands. It emphasizes the role of hospital and community transmission control measures in addition to the timely administration of antiviral treatment in reducing the burden of a flu pandemic. The latter is consistent with the preparedness plans of the UK and the Netherlands. Our results indicate that for low efficacy and coverage levels of antivirals and vaccine, the use of a vaccine leads to the greatest reduction in morbidity and mortality compared with the singular use of antivirals. However, as these efficacy and coverage levels are increased, the use of antivirals is more effective.
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Yaqinuddin, Ahmed, Areez Shafqat, Junaid Kashir, and Khaled Alkattan. "Effect of SARS-CoV-2 Mutations on the Efficacy of Antibody Therapy and Response to Vaccines." Vaccines 9, no. 8 (August 17, 2021): 914. http://dx.doi.org/10.3390/vaccines9080914.
Full textAbstract:
SARS-CoV-2 causes severe acute respiratory syndrome, which has led to significant morbidity and mortality around the world. Since its emergence, extensive prophylactic and therapeutic countermeasures have been employed to successfully prevent the spread of COVID-19. Extensive work has been undertaken on using monoclonal antibody therapies, mass vaccination programs, and antiviral drugs to prevent and treat COVID-19. However, since antiviral drugs could take years to become widely available, immunotherapy and vaccines currently appear to be the most feasible option. In December 2020, the first vaccine against SARS-CoV-2 was approved by the World Health Organization (WHO) and, subsequently, many other vaccines were approved for use by different international regulators in different countries. Most monoclonal antibodies (mAbs) and vaccines target the SARS-CoV-2 surface spike (S) protein. Recently, mutant (or variant) SARS-CoV-2 strains with increased infectivity and virulence that evade protective host antibodies present either due to infection, antibody therapy, or vaccine administration have emerged. In this manuscript, we discuss the different monoclonal antibody and vaccine therapies available against COVID-19 and how the efficacy of these therapies is affected by the emergence of variants of SARS-CoV-2. We also discuss strategies that might help society cope with variants that could neutralize the effects of immunotherapy and escape the protective immunity conferred by vaccines.
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Mortazavi, Alireza, Seyed Mohammad Javad Mortazavi, and Lembit Sihver. "Selective Pressure-Free Treatments for COVID-19." Radiation 1, no. 1 (December 2, 2020): 18–32. http://dx.doi.org/10.3390/radiation1010003.
Full textAbstract:
The new severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused more than 40 million human infections since December 2019, when a cluster of unexplained pneumonia cases was first reported in Wuhan, China. Just a few days after the coronavirus was officially recognized, it was identified as the causative agent of this mysterious pneumonia. This paper discusses the pros and cons of antiviral drugs from the selective pressure and possible drug resistance point of view. We also address the key advantages of potential selective pressure-free treatment methods such as the use of sparsely and densely ionizing low-dose radiation (LDR). It is known that LDR has the capacity to modulate excessive inflammatory responses, regulate lymphocyte counts and control bacterial co-infections in patients with COVID-19 and different modalities. Substantial evidence shows that viruses are constantly mutating and evolving. When an antiviral immune response is unable to eliminate a virus, viral evolution is promoted. Therefore, it is of crucial importance to limit the use of antivirals/vaccines against SARS-CoV-2 when their effects on viral fitness are not fully understood. Furthermore, to limit the spread of the virus, it is essential to develop a vaccine that is available for as many people as possible. However, with the advent of vaccines or new therapies, the new situation may force the virus to evolve. Given this consideration, selective pressure-free treatments for COVID-19 are of great importance.
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Zeng, Sen, Yuwan Li, Wenhui Zhu, Zipeng Luo, Keke Wu, Xiaowen Li, Yiqi Fang, et al. "The Advances of Broad-Spectrum and Hot Anti-Coronavirus Drugs." Microorganisms 10, no. 7 (June 26, 2022): 1294. http://dx.doi.org/10.3390/microorganisms10071294.
Full textAbstract:
Coronaviruses, mainly including severe acute respiratory syndrome virus, severe acute respiratory syndrome coronavirus 2, Middle East respiratory syndrome virus, human coronavirus OC43, chicken infectious bronchitis virus, porcine infectious gastroenteritis virus, porcine epidemic diarrhea virus, and murine hepatitis virus, can cause severe diseases in humans and livestock. The severe acute respiratory syndrome coronavirus 2 is infecting millions of human beings with high morbidity and mortality worldwide, and the multiplicity of swine epidemic diarrhea coronavirus in swine suggests that coronaviruses seriously jeopardize the safety of public health and that therapeutic intervention is urgently needed. Currently, the most effective methods of prevention and control for coronaviruses are vaccine immunization and pharmacotherapy. However, the emergence of mutated viruses reduces the effectiveness of vaccines. In addition, vaccine developments often lag behind, making it difficult to put them into use early in the outbreak. Therefore, it is meaningful to screen safe, cheap, and broad-spectrum antiviral agents for coronaviruses. This review systematically summarizes the mechanisms and state of anti-human and porcine coronavirus drugs, in order to provide theoretical support for the development of anti-coronavirus drugs and other antivirals.
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Alpatova, N. A., Zh I. Avdeeva, L. A. Gayderova, S. L. Lysikova, and N. V. Medunitsyn. "Immune Response Induced by Immunisation with Antiviral Vaccines." BIOpreparations. Prevention, Diagnosis, Treatment 20, no. 1 (March 25, 2020): 21–29. http://dx.doi.org/10.30895/2221-996x-2020-20-1-21-29.
Full textAbstract:
The review is devoted to specific aspects of the development of post-vaccination immunity following immunisation with different types of antiviral vaccines, as well as to ways of increasing immunogenicity of vaccines and effectiveness of preventive vaccination. Vaccines containing highly purified and recombinant antigens obtained using modern technologies have lower reactogenicity and a higher safety profile, but are less immunogenic compared to live vaccines. Effective vaccines have not been developed for many viral infections yet. Therefore, it is critical to search for ways to enhance immunogenic properties of vaccines in order to increase the efficiency of vaccination, and to develop new vaccine formulations that provide reliable protection of the body against infection. The aim of the paper was to analyse specific aspects of immune response development following immunisation with antiviral vaccines, and approaches to increasing their immunogenicity using adjuvants. It reviews different types of antiviral vaccines, as well as specific aspects of immune response development depending on the nature of a specific antigen. The paper substantiates the use of adjuvants to enhance and regulate the induced immune response. It analyses mechanisms that determine the stimulating effect of adjuvants and summarises data on the adjuvants used in the licensed vaccines for human use. The authors highlight the need for further research to increase the efficiency of vaccination and suggest that one of potential solutions is the use of adjuvants based on recombinant human cytokines.
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Zarkesh, Khatereh, Mohsen Akbarian, Lobat Tayebi, Vladimir N. Uversky, Alberto Rubio-Casillas, and Elrashdy M. Redwan. "Harnessing Antiviral Peptides as Means for SARS-CoV-2 Control." COVID 3, no. 7 (June 29, 2023): 975–86. http://dx.doi.org/10.3390/covid3070070.
Full textAbstract:
Several times during the past two decades, epidemic viral diseases created global challenges. Although many solutions have been proposed to deal with this tight spot, it is still believed that public vaccination represents the most effective strategy to handle it. So far, various kinds of vaccines including protein subunits, virus-like particles, inactivated, live attenuated, viral vectors, RNA, and DNA vaccines have been used in the prevention of COVID-19. Among the various categories of vaccines, peptide vaccines have created a new hope for quick and trustworthy access due to the development of proteomics equipment. This review specifically focuses on vaccines and peptide therapies in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We consider here the efficacy and safety of subunit and synthetic peptides vaccine in clinical trial phases. Furthermore, monoclonal antibodies with the ability to suppress the development of SARS-CoV-2, those candidates that have entered into clinical trials until March 2023, were selected and evaluated.
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Lemon, Stanley M., and Julie B. Milstien. "The Thermostability of Vaccines: Technologies for Improving the Thermostability of the Oral Poliovirus Vaccine." International Journal of Technology Assessment in Health Care 10, no. 1 (1994): 177–84. http://dx.doi.org/10.1017/s0266462300014100.
Full textAbstract:
AbstractTechnologies that promise to enhance the stability of vaccines are likely to be determined by the product-specific physical structure and biological functions of the specific vaccine immunogens. Research may define the extent to which the stability of oral poliovirus vaccine may be improved by the addition of certain antiviral components that bind to the poliovirus capsid or by the application of novel drying technologies.
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Strizova, Zuzana, Jitka Smetanova, Jirina Bartunkova, and Tomas Milota. "Principles and Challenges in anti-COVID-19 Vaccine Development." International Archives of Allergy and Immunology 182, no. 4 (2021): 339–49. http://dx.doi.org/10.1159/000514225.
Full textAbstract:
The number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients keeps rising in most of the European countries despite the pandemic precaution measures. The current antiviral and anti-inflammatory therapeutic approaches are only supportive, have limited efficacy, and the prevention in reducing the transmission of SARS-CoV-2 virus is the best hope for public health. It is presumed that an effective vaccination against SARS-CoV-2 infection could mobilize the innate and adaptive immune responses and provide a protection against severe forms of coronavirus disease 2019 (COVID-19) disease. As the race for the effective and safe vaccine has begun, different strategies were introduced. To date, viral vector-based vaccines, genetic vaccines, attenuated vaccines, and protein-based vaccines are the major vaccine types tested in the clinical trials. Over 80 clinical trials have been initiated; however, only 18 vaccines have reached the clinical phase II/III or III, and 4 vaccine candidates are under consideration or have been approved for the use so far. In addition, the protective effect of the off-target vaccines, such as <i>Bacillus</i> Calmette-Guérin and measles vaccine, is being explored in randomized prospective clinical trials with SARS-CoV-2-infected patients. In this review, we discuss the most promising anti-COVID-19 vaccine clinical trials and different vaccination strategies in order to provide more clarity into the ongoing clinical trials.