Self-Replicating RNA

Tews, Birke Andrea; Meyers, Gregor

doi:10.1007/978-1-4939-6481-9_2

Cited by 47 publications

(34 citation statements)

References 85 publications

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“…However, several disadvantages exist, including (i) select agent restrictions, (ii) packaging and safety testing under BSL3 conditions, (iii) potential generation of wild-type VEE virus due to RNA recombination, (iv) potential generation of replication competent viruses, and (v) failure of VRP 3014 vaccines to protect aged populations against homologous and heterologous virus challenge ( 17 ). Strategies to circumvent this problem have included the use of multiple helper RNAs, alphavirus replicon-based adjuvants, or RNA- and DNA-based replicon launch platforms in the absence of structural proteins ( 13 , 33 – 35 ). In the manuscript, we have developed and characterized the VRP 3526 platform as a highly portable and safe vector platform for expression of novel genes with features similar to those of the earlier VRP 3000 and VRP 3014 iterations.…”

Section: Discussionmentioning

confidence: 99%

Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform

Agnihothram

Menachery

Yount

et al. 2018

J Virol

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Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine, strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the VRP 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. Importantly, packaging under biosafety level 2 (BSL2) conditions distinguishes VRP 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. In addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated VRP approaches. Taking these results together, the VRP 3526 platform represents a safe and highly portable system that can be rapidly deployed under BSL2 conditions for generation of candidate vaccines against emerging microbial pathogens.IMPORTANCE While VEE virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. In this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. Importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. Together, the new system represents a highly portable, safe system for use in the context of disease emergence.

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Section: Discussionmentioning

confidence: 99%

Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform

Agnihothram

Menachery

Yount

et al. 2018

J Virol

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“…Self-amplifying mRNA vaccines are commonly based on the engineered RNA genome of positive-sense single-stranded RNA viruses, such as alphaviruses, flaviviruses, and picornaviruses. 81,82 In all cases, the mRNA mimics the replicative features of positive-sense singlestranded RNA viruses with the goal of increasing the duration and magnitude of the expression, as well as subsequent immunogenicity of the encoded antigen. The best-studied self-amplified mRNA molecules are derived from alphavirus genomes, such as those of the Sindbis virus (SINV), Semliki Forest virus (SFV), and Venezuelan equine encephalitis viruses (VEEVs) (reviewed in Ljungberg and Liljeström 83 and Atkins et al 84 ).…”

Section: Self-amplifying Mrna Vaccinesmentioning

confidence: 99%

mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases

et al. 2019

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“…Further, to have a SAM construct we used the genes encoding non-structural proteins (nsp) of Semliki Forest virus (NCBI reference sequence: NC_003215.1) as a genomic (+) single-strand RNA alphavirus 104 .…”

Section: Designing the Candidate Vaccine Constructsmentioning

confidence: 99%

Prophylactic domain-based vaccine against SARS-CoV-2, causative agent of COVID-19 pandemic

Pourseif

Parvizpour

Jafari

et al. 2020

Preprint

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Coronavirus disease 2019 (COVID-19) is undoubtedly the most challenging pandemic in the current century with more than 253,381 deaths worldwide since its emergence in late 2019 (updated May 6th, 2020). COVID-19 is caused by a novel emerged coronavirus named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Today, the world needs crucially to develop a prophylactic vaccine scheme for such emerged and emerging infectious pathogens. In this study, we have targeted spike (S) glycoprotein, as an important surface antigen of SARS-CoV-2, to identify its immunodominant B- and T-cell epitopes. We have conducted a multi-method B-cell epitope (BCE) prediction approach using different predictor algorithms to discover most potential BCEs. Besides, we sought among a pool of MHC class I and II-associated peptide binders provided by the IEDB server through the strict cut-off values. To design a broad-coverage vaccine, we carried out a population coverage analysis for a set of candidate T-cell epitopes and based on the HLA allele frequency in the top most-affected countries by COVID-19 (update 02 April 2020). The final determined B- and T-cell epitopes were mapped on the S glycoprotein sequence, and three potential hub regions covering the largest number of overlapping epitopes were identified for the vaccine designing (I531–N711; T717–C877; and V883–E973). Here, we have designed two domain-based constructs to be produced and delivered through the recombinant protein- and gene-based approaches, including (i) an adjuvanted domain-based protein vaccine construct (DPVC), and (ii) a self-amplifying mRNA vaccine (SAMV) construct. The safety, stability, and immunogenicity of the DPVC were validated using the integrated sequential (i.e. allergenicity, autoimmunity, and physicochemical features) and structural (i.e. molecular docking between the vaccine and human Toll-like receptors (TLRs) 4 and 5) analysis. The stability of the docked complexes was evaluated using the molecular dynamics (MD) simulations. These rigorous in silico validations supported the potential of the DPVC and SAMV to promote both innate and specific immune responses in the animal studies.

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Self-Replicating RNA

Cited by 47 publications

References 85 publications

Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform

Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform

mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases

Prophylactic domain-based vaccine against SARS-CoV-2, causative agent of COVID-19 pandemic

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