scholarly journals Plant-based production of SARS-CoV-2 antigens for use in a subunit vaccine

2021 ◽  
Author(s):  
Jordan J Demone ◽  
Mariam Maltseva ◽  
Maryam Nourimand ◽  
Mina Nasr-Sharif ◽  
Yannick Galipeau ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Rapid Development ◽  
Cost Effective ◽  
Wild Type ◽  
In Planta ◽  
Vaccine Platform ◽  
Angiotensin Converting Enzyme 2 ◽  
Viral Glycoproteins ◽  
A Subunit ◽  
Multiple Variants

The COVID-19 pandemic has brought to the forefront an urgent need for the rapid development of highly efficacious vaccines, particularly in light of the ongoing emergence of multiple variants of concern. Plant-based recombinant protein platforms are emerging as cost-effective and highly scalable alternatives to conventional protein production. Viral glycoproteins, however, are historically challenging to produce in plants. Herein, we report the production of plant-expressed wild-type glycosylated SARS-CoV-2 Spike RBD (receptor-binding domain) protein that is recognized by anti-RBD antibodies and exhibits high-affinity binding to the SARS-CoV-2 receptor ACE2 (angiotensin-converting enzyme 2). Moreover, our plant-expressed RBD was readily detected by IgM, IgA, and IgG antibodies from naturally infected convalescent, vaccinated, or convalescent and vaccinated individuals. We further demonstrate that RBD binding to the ACE2 receptor was efficiently neutralized by antibodies from sera of SARS-CoV-2 convalescent and partially and fully vaccinated individuals. Collectively, these findings demonstrate that recombinant RBD produced in planta exhibits suitable biochemical and antigenic features for use in a subunit vaccine platform.

scholarly journals Cryo-EM structure of S-Trimer, a subunit vaccine candidate for COVID-19

2020 ◽  
Author(s):  
Jiahao Ma ◽  
Danmei Su ◽  
Xueqin Huang ◽  
Ying Liang ◽  
Yan Ma ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Full Length ◽  
Wild Type ◽  
S Protein ◽  
Closed Conformation ◽  
Death Toll ◽  
Platform Technology ◽  
A Subunit

AbstractLess than a year after its emergence, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 22 million people worldwide with a death toll approaching 1 million. Vaccination remains the best hope to ultimately put this pandemic to an end. Here, using Trimer-Tag technology, we produced both wild-type (WT) and furin site mutant (MT) S-Trimers for COVID-19 vaccine studies. Cryo-EM structures of the WT and MT S-Trimers, determined at 3.2 Å and 2.6 Å respectively, revealed that both antigens adopt a tightly closed conformation and their structures are essentially identical to that of the previously solved full-length WT S protein in detergent. These results validate Trimer-Tag as a platform technology in production of metastable WT S-Trimer as a candidate for COVID-19 subunit vaccine.

scholarly journals Overexpression of OsABCG48 Lowers Cadmium in Rice (Oryza sativa L.)

Agronomy ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 918
Author(s):  
Xingzhe Cai ◽  
Meng Wang ◽  
Yucong Jiang ◽  
Changhu Wang ◽  
David W. Ow
Keyword(s):  
Oryza Sativa L ◽  
Cost Effective ◽  
Health Issues ◽  
Rna Seq ◽  
Wild Type ◽  
Genetic Changes ◽  
Cd Accumulation ◽  
Lateral Root Development ◽  
Atp Binding Cassette Transporter ◽  
Cost Effective Approach

Cadmium pollution threatens food safety and security by causing health issues and reducing farmland availability. Engineering genetic changes in crop plants to lower Cd accumulation can be a cost-effective approach to address this problem. Previously, we reported that a rice line, 2B, which expresses a truncated version of OsO3L2 had reduced Cd accumulation throughout the plant, including in seed. However, downstream events caused by expression of this gene were not known. In this study, RNA-seq was used to identify differentially expressed genes between the wild type and 2B rice with or without Cd treatment, leading to the study of an ABC transporter gene, OsABCG48 (ATP-Binding Cassette transporter G family member 48). Heterologous expression of OsABCG48 conferred tolerance to Cd in Schizosaccharomyces pombe, Arabidopsis and rice. Moreover, overexpressing OsABCG48 in rice lowered root Cd accumulation that was associated with more extensive lateral root development. These data suggest that OsABCG48 might have applications for engineering low-Cd rice.

scholarly journals Challenges for Evaluation of the Safety of Engineered Nanomaterials

2021 ◽  
Vol 43 (1) ◽  
pp. 4-7
Author(s):  
Linda J. Johnston ◽  
Norma Gonzalez-Rojano ◽  
Kevin J. Wilkinson ◽  
Baoshan Xing
Keyword(s):  
Rapid Development ◽  
Sustainable Use ◽  
Cost Effective ◽  
Engineered Nanomaterials ◽  
Full Potential ◽  
Effective Strategies ◽  
Toxicological Studies ◽  
Regulatory Guidelines ◽  
Significant Effort ◽  
Safe By Design

Abstract Nanotechnology has developed rapidly in the last two decades with significant effort focused on the development of nano-enabled materials with new or improved properties that offer solutions for current world challenges. The commercialization of products containing engineered nanomaterials (ENM) has progressed much more rapidly than the development of practical approaches to ensure their safe and sustainable use. The lack of adequate detection and characterization techniques and reproducible and validated methods for toxicological studies have been identified as major limitations. The rapid development of ENM of increasing complexity and diversity and concerns over the adequacy of existing regulations also contribute to safety concerns with these materials. The full potential of nanotechnology can only be realized when feasible, cost-effective strategies to ensure a safe-by-design approach, effective risk assessment approaches and appropriate regulatory guidelines are in place.

scholarly journals Evaluation of a subunit vaccine candidate (Biotech Vac Cox) against Eimeria spp. in broiler chickens

2021 ◽  
pp. 101329
Author(s):  
Emanuel Gumina ◽  
Jeffrey W. Hall ◽  
Bruno Vecchi ◽  
Xochitl Hernandez-Velasco ◽  
Brett Lumpkins ◽  
...  
Keyword(s):  
Broiler Chickens ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Eimeria Spp ◽  
A Subunit

Recent Advances on Visible-Light-Promoted Copper Catalysis in Organic Reactions

Synthesis ◽  
2021 ◽  
Author(s):  
Yang Xiong ◽  
Sijia Li ◽  
Haijing Xiao ◽  
Guozhu Zhang
Keyword(s):  
Visible Light ◽  
Copper Complexes ◽  
Rapid Development ◽  
Cost Effective ◽  
Organic Reactions ◽  
Copper Catalysis ◽  
Synthetic Chemistry ◽  
Recent Advances ◽  
Intense Activity

In recent years, visible-light-mediated copper photocatalysis have emerged as an attractive strategy for the diverse constructions of basic bonds in an ecologically benign and cost-effective fashion. The intense activity and increasing work of these areas stimulated the exploit of the distinctive properties of copper photocatalysis and the rapid development and expansion of their applications. In this review, we focus on introducing a series of significant achievements in copper complexes as standalone photocatalysis in organic reactions to make an attempt to exhibit their potential capabilities and high flexibilities in synthetic chemistry.

scholarly journals “Hijacking” the Thyrotropin Receptor: A Chimeric Receptor-Lysosome Associated Membrane Protein Enhances Deoxyribonucleic Acid Vaccination and Induces Graves’ Hyperthyroidism

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5504-5514 ◽  
Author(s):  
Pavel N. Pichurin ◽  
Gregorio D. Chazenbalk ◽  
Holly Aliesky ◽  
Oxana Pichurina ◽  
Basil Rapoport ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Membrane Protein ◽  
Major Histocompatibility Complex Class ◽  
Inhibitory Activity ◽  
Dna Vaccination ◽  
Complex Class ◽  
Wild Type ◽  
Naked Dna ◽  
Histocompatibility Complex ◽  
A Subunit

Abstract Naked DNA vaccination with the TSH receptor (TSHR) does not, in most studies, induce TSHR antibodies and never induces hyperthyroidism in BALB/c mice. Proteins expressed endogenously by vaccination are preferentially presented by major histocompatibility complex class I, but optimal T cell help for antibody production requires lysosomal processing and major histocompatibility complex class II presentation. To divert protein expression to lysosomes, we constructed a plasmid with the TSHR ectodomain spliced between the signal peptide and transmembrane-intracellular region of lysosome-associated membrane protein (LAMP)-1, a lysosome-associated membrane protein. BALB/c mice pretreated with cardiotoxin were primed intramuscularly using this LAMP-TSHR chimera and boosted twice with DNA encoding wild-type TSHR, TSHR A-subunit, or LAMP-TSHR. With each protocol, spleen cells responded to TSHR antigen by secreting interferon-γ, and 60% or more mice had TSHR antibodies detectable by ELISA. TSH binding inhibitory activity was present in seven, four, and two of 10 mice boosted with TSHR A-subunit, LAMP-TSHR, or wild-type TSHR, respectively. Importantly, six of 30 mice had elevated T4 levels and goiter (5 of 6 with detectable thyroid-stimulating antibodies). Injecting LAMP-TSHR intradermally without cardiotoxin pretreatment induced TSHR antibodies detectable by ELISA but not by TSH binding inhibitory activity, and none became hyperthyroid. These findings are consistent with a role for cardiotoxin-recruited macrophages in which (unlike in fibroblasts) LAMP-TSHR can be expressed intracellularly and on the cell surface. In conclusion, hijacking the TSHR to lysosomes enhances T cell responses and TSHR antibody generation and induces Graves’-like hyperthyroidism in BALB/c mice by intramuscular naked DNA vaccination.

Identification of a DNA region required for growth of Pseudomonas syringae pv. tomato on tomato plants

1992 ◽  
Vol 38 (9) ◽  
pp. 883-890 ◽  
Author(s):  
Dennis P. Jackson ◽  
Douglas A. Gray ◽  
Vincent L. Morris ◽  
Diane A. Cuppels
Keyword(s):  
Organic Acids ◽  
Pseudomonas Syringae ◽  
Acid Metabolism ◽  
Carbon Sources ◽  
Hypersensitive Reaction ◽  
Wild Type ◽  
In Planta ◽  
Tomato Plants ◽  
Tartaric Acids ◽  
Nonpathogenic Strain

The prototrophic Pseudomonas syringae pv. tomato mutant DC3481, which is the result of a single-site Tn5 insertion, cannot grow and cause disease on tomato plants and cannot use the major organic acids of tomato, i.e., citric, malic, succinic, and tartaric acids, as sole carbon sources. Although nonpathogenic, strain DC3481 can still induce a hypersensitive reaction in nonhost plants. We have identified a 30-kb fragment of P. syringae pv. tomato wild-type DNA that can complement this mutant. EcoRI fragments from this region were subcloned and individually subjected to functional complementation analysis. The 3.8-kb fragment, which was the site of the Tn5 insertion, restored pathogenicity and the ability to use all the major organic acids of tomato as carbon sources. It shares sequence homology with several P. syringae pathovars but not other bacterial tomato pathogens. Our results indicate that sequences on the 3.8-kb EcoRI fragment are required for both the ability to grow on tomato leaves (and thus cause disease) and the utilization of carboxylic acids common to tomato. The 3.8-kb fragment may contain a sequence (or sequences) that regulates both traits. Key words: Pseudomonas syringae pv. tomato, phytopathogenicity, Tn5, tricarboxylic acid metabolism, bacterial speck, growth in planta.

scholarly journals The next generation of RNA vaccines: self-amplifying RNA

2021 ◽  
Author(s):  
Anna Blakney
Keyword(s):  
Side Effects ◽  
Messenger Rna ◽  
Rapid Development ◽  
Next Generation ◽  
High Efficacy ◽  
Vaccine Platform ◽  
The Future ◽  
High Doses ◽  
The Stability

The global COVID-19 pandemic has brought tremendous momentum to the field of messenger RNA (mRNA) vaccines. The advantages of this vaccine platform, such as rapid development and high efficacy, resulted in mRNA vaccines being the first approved vaccines against COVID-19. Looking forward to the development of future vaccines, how can we make RNA vaccines even better? While improvements in the stability of the formulation and cost of the vaccine are inevitable, one of the main challenges is lowering the dose of RNA in order to avoid side effects associated with high doses of RNA. One way to do this is by using self-amplifying RNA (saRNA), a type of mRNA that encodes a replicase that copies the original strand of RNA once it’s in the cell. Here, we discuss the origins of saRNA, how it works in comparison to mRNA, current challenges in the field and the future of saRNA vaccines.

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