During the last decade, a wide variety of cellular RNA sensors and structural characteristics of their agonists have been identified. On the basis of this knowledge, RNA formulations were developed as innovative adjuvant candidates. In contrast to DNA, RNA does not have genotoxic potential and is rapidly degraded. In many aspects, RNA mimics viral infections and induces considerably strong immune responses. Additionally, RNA-based adjuvants can be designed so that distinct RNA sensors can be triggered according to requirements of individual vaccines. Furthermore, RNA can be synthesized in vitro in a cell-free system, and recent developments in formulation technology have led to reduced RNA degradation within the body. These features qualify RNA as a promising adjuvant candidate. Here, we discuss latest developments in the field of RNA-based adjuvants and highlight differences between human and mouse nucleic acid sensors, which constitute a challenge in the development of RNA-based adjuvants. Finally, we discuss how RNA-based adjuvants are currently handled with regard to regulatory requirements.
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June 1985 · The Quarterly Review of Biology Read more April 2016 · Methods in molecular biology (Clifton, N.J.)
DNA vaccines present the aquaculture industry with an effective and economically viable method of controlling viral pathogens that drastically affect productivity. Since specific immune response is rudimentary in invertebrates, the presence of RNA interference (RNAi) pathway in shrimps provides a promising new approach to vaccination. Plasmid DNA vaccines that express short or long double
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It was recently reported that Poly(I:C) immunization of fish confers protection against viral infection. In this process, fish are immunized with a live pathogenic virus followed by administration of Poly(I:C), which induces a transient, non-specific antiviral state. As a result, fish survive the initial immunization with live virus, which would otherwise be lethal. In the present study, we tried
... [Show full abstract] to determine the exact dosage of red-spotted grouper nervous necrosis virus (RGNNV), the causative agent of viral nervous necrosis, required for Poly(I:C) immunization of sevenband grouper Epinephelus septemfasciatus. In Poly(I:C) immunization with more than 90% relative percentage survival (RPS) against RGNNV challenge with 104.3 TCID50/fish, approximately 104.0 TCID50/fish or greater of RGNNV was administered by intramuscular (IM) injection, whereas 105.3 TCID50/fish or greater of RGNNV was required for immersion methods. It was concluded that the degree of RGNNV infection must be similar to a fatal dose in order for the fish to become immune to RGNNV. Interestingly, antibody against RGNNV was not detected in the sera of fish immunized by immersion. Thus, Poly(I:C) immunization by immersion may have some interesting effects on the epidermal immune response in fish. Read more Article Full-text available June 2017 · mSphere
Norovirus is the leading cause of acute gastroenteritis worldwide. For over two decades, a single genotype (GII.4) has been responsible for most norovirus-associated cases. However, during the winter of 2014 to 2015, the GII.4 strains were displaced by a rarely detected genotype (GII.17) in several countries of the Asian continent. Moreover, during the winter of 2016 to 2017, the GII.2 strain
... [Show full abstract] reemerged as predominant in different countries worldwide. This reemerging GII.2 strain is a recombinant virus that presents a GII.P16 polymerase genotype. In this study, we investigated the evolutionary dynamics of GII.2 to determine the mechanism of this sudden emergence in the human population. The phylogenetic analyses indicated strong linear evolution of the VP1-encoding sequence, albeit with minor changes in the amino acid sequence over time. Without major genetic differences among the strains, a clustering based on the polymerase genotype was observed in the tree. This association did not affect the substitution rate of the VP1. Phylogenetic analyses of the polymerase region showed that reemerging GII.P16-GII.2 strains diverged into a new cluster, with a small number of amino acid substitutions detected on the surface of the associated polymerase. Thus, besides recombination or antigenic shift, point mutations in nonstructural proteins could also lead to novel properties with epidemic potential in different norovirus genotypes.
IMPORTANCE Noroviruses are a major cause of gastroenteritis worldwide. Currently, there is no vaccine or specific antiviral available to treat norovirus disease. Multiple norovirus strains infect humans, but a single genotype (GII.4) has been regarded as the most important cause of viral gastroenteritis outbreaks worldwide. Its persistence and predominance have been explained by the continuous replacement of variants that present new antigenic properties on their capsid protein, thus evading the herd immunity acquired to the previous variants. Over the last three seasons, minor genotypes have displaced the GII.4 viruses as the predominant strains. One of these genotypes, GII.2, reemerged as predominant during 2016 to 2017. Here we show that factors such as minor changes in the polymerase may have driven the reemergence of GII.2 during the last season. A better understanding of norovirus diversity is important for the development of effective treatments against noroviruses. View full-text December 2008
Herpes Zoster is seen most frequently in the elderly population and its diagnosis is mainly clinical. In the elderly, it exposes to complications, in particular herpes zoster ophthalmicus and postherpetic neural gias (PHN). The treatment of the acute phase differs from the chronic phase. The acute phase treatment includes topical therapy, analgesics and antiviral whatever is the immunological
... [Show full abstract] status of the patient. The more the antiviral treatment is administered early, the more it will prevent PHN. At the chronic phase, PHN, major complications of herpes zoster in the elderly, are difficult to treat. Tricyclic antidepressants associated with anti-epilep tics have showed a definite efficiency but their side effects limit their use. The psychological support in team remains essential and fundamental in the global care of the elderly. The arrival of antiviral vaccine seems to be promising. Read more May 2015 · Majalah Kedokteran Andalas
AbstrakVirus dengue (DENV) telah menyebabkan sekitar 50 juta kasus infeksi demam berdarah setiap tahunnya, akan tetapi hingga saat ini belum terdapat vaksin maupun antivirus yang mampu mencegah atau mengobati penyakit tersebut. Selama pengembangan vaksin dan antivirus, diperoleh berbagai informasi tentang struktur protein DENV yang dapat dimanfaatkan sebagai target obat. Makalah membahas tentang
... [Show full abstract] struktur proteomik pada DENV, yaitu glikoprotein pada envelope, NS3 protease, NS3 helikase, NS5 metiltransferase, dan NS5 RNA-dependent RNA polimerase.AbstractDengue virus (DENV) has caused over 50 millions infection every year. However, to date neither vaccine nor medicine could be used to prevent or cure the illness. During researches in finding the vaccine or antiviral for DENV, information on DENV protein structure has been obtained which is potentially used as drug target. This paper disscuss DENV proteomic structure that consist of envelope glicoprotein, NS3 protease, NS3 helicase, NS5 methyl-transferase, and NS5 RNA-dependent RNA polymerase. Read more August 2009 · Current Topics in Medicinal Chemistry
The naturally-occurring RNA interference (RNAi) pathway represents a powerful tool for the sequence-specific post-transcriptional silencing of gene expression. By exploiting the endogenous mammalian RNAi pathway, several expression-based strategies have been developed to inhibit human immunodeficiency virus (HIV) gene expression and replication. This approach potentially has utility as a
... [Show full abstract] protective 'therapeutic vaccine' of virus-susceptible lymphocytes. In this review we discuss new developments aimed at improving efficacy and delivery of novel RNAi-based gene expression antiviral strategies. Particular attention is given to advances in combinatorial gene expression systems that prevent the emergence of RNAi-resistant virus by simultaneously targeting multiple HIV targets. Potential usefulness of silencing host factors that are required for viral replication is also discussed. These approaches form the basis for a number of promising ongoing and future clinical trials aimed at providing an effective, safe and prolonged single-intervention therapy for HIV/AIDS. Read more May 2017 · Rheumatology (Oxford, England)
Chickenpox and shingles can be more severe and occasionally life threatening in immunosuppressed patients. As such, some groups warrant a more detailed history, serological testing and consideration of prophylaxis following contact with the virus. Active disease may also require more aggressive treatment with antivirals. Guidance for the use of varicella zoster immunoglobulin has recently been
... [Show full abstract] updated by Public Health England with important implications for rheumatology patients. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. Read more July 2017 · Expert Review of Vaccines
Introduction: The present review summarizes the growing body of work defining the mechanisms of action of this exciting new vaccine technology that should allow rational approaches in the design of next generation mRNA vaccines.
Areas covered: Bio-distribution of mRNA, localization of antigen production, role of the innate immunity, priming of the adaptive immune response, route of administration
... [Show full abstract] and effects of mRNA delivery systems.
Expert commentary: In the last few years, the development of RNA vaccines had a fast growth, the rising number of proof will enable rational approaches to improving the effectiveness and safety of this modern class of medicine. Read more May 1999 · Proceedings of The Society for Experimental Biology and Medicine
An alternative model to nonhuman primates to study measles virus (MV) pathogenesis, to evaluate potential MV vaccines, or to screen for potential antivirals effective against this virus is highly desirable. The laboratory-adapted Edmonston strain of MV has been reported to replicate in the lungs of hispid cotton rats following intranasal inoculation, immunosuppress infected animals, and
... [Show full abstract] disseminate widely from the lungs, making these animals a candidate model. However, clinical MV strains have generally not been found to grow in these animals, limiting the utility and acceptance of this model. In the present studies we demonstrate reproducible replication of several clinical MV strains in hispid cotton rats. As with the Edmonston strain, leukocytes appear to be the primary target cells of these viruses following intranasal inoculation, and extrapulmonary dissemination is common. It is also demonstrated that prior MV infection or immunization of test animals with MV vaccine prevents pulmonary tract infection. These findings should make the MV-cotton rat model more acceptable. Read more May 2018 · Advances in Experimental Medicine and Biology
Dengue fever is a leading cause of illness and mortality in the tropics and subtropics. There are no therapeutics currently available and a recently approved vaccine is not very efficacious demanding an urgent need to develop an effective antiviral. The path to successful dengue drug development depends on availability of relevant preclinical testing models and better understanding of dengue
... [Show full abstract] pathogenesis. In recent years, efforts to develop dengue therapeutics have focused on both repurposing approved drugs as well as discovery of new chemical entities that act via virus or host targeted mechanisms. Here, we discuss the various innovative approaches, their outcome, and the lessons gleaned from the development efforts. Read more Last Updated: 30 Oct 2020 Looking for the full-text?
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