Characterization of stability, safety and immunogenicity of the mRNA lipid nanoparticle vaccine Iribovax® against COVID-19 in nonhuman primates.

mRNA-lipid nanoparticle (mRNA-LNP) vaccines have proved their efficacy, versatility and unprecedented manufacturing speed during the COVID-19 pandemic. Here we report on the physicochemical properties, thermostability, immunogenicity, and protective efficacy of the nucleoside-modified mRNA-LNP vaccine candidate Iribovax® (also called SNEG2c). Injection of BALB/c mice, rabbits and nonhuman primates with two doses of SNEG2c induced production of high-titers of SARS-CoV-2 spike-specific and receptor-binding domain (RBD)-neutralizing antibodies in immunized animals. In addition to the strong humoral response, SNEG2c elicited substantial Th1-biased T-cell response. Sera from rhesus macaques immunized with a low dose of the vaccine showed robust spike-specific antibody titers 3-24× as high as those in convalescent sera from a panel of COVID-19 patients and 50% virus neutralization geometric mean titer of 1024 against SARS-CoV-2. Strikingly, immunization with SNEG2c completely cleared infectious SARS-CoV-2 from the upper and lower respiratory tracts of challenged macaques and protected them from viral-induced lung and trachea lesions. In contrast, the non-vaccinated macaques developed moderate to severe pulmonary pathology after the viral challenge. We present the results of repeat-dose and local tolerance toxicity and thermostability studies showing how the physicochemical properties of the mRNA-LNPs change over time and demonstrating that SNEG2 is safe, well tolerated and stable for long-term. These results support the planned human trials of SNEG2c.

Onion (Allium cepa) and its Main Constituents as Antidotes or Protective Agents against Natural or Chemical Toxicities: A Comprehensive Review.

Onion (Allium cepa) is a member of the family Amaryllidaceae and one of the most widely cultivated species of the genus Allium. Onion has plentiful chemical compounds such as allicin, quercetin, fisetin, other sulphurous compounds: diallyl disulphide and diallyl trisulphide. Onion and its main components in specific doses have shown a lot of benefits including free-radical scavenging and antioxidant properties, anticholesterolemic, anti-heavy metals toxicity, antihyperuricemia, antimicrobial, anti-gastric ulcer, and anticancer. This study summarizes numerous in-vitro and animal studies on the protective effects of onion against natural and chemical toxicities. Onion and its main components can ameliorate the toxicity of chemical agents in kidney, liver, brain, blood, heart, reproductive system, embryo, pancreas through reducing lipid peroxidation, antioxidant effect, radical-scavenging, anti-inflammatory, chelating agent, cytoprotective activities, increasing protein synthesis in damaged tissues, suppressing apoptosis, as well as modulation of PKC-𝜀/p38MAPK, Wnt/beta-Catenin, ERK, JNK, p38 MAPK, Bcl-2, Bax, and NF-κB signaling pathways.

Garlic (Allium sativum) as an antidote or a protective agent against natural or chemical toxicities: A comprehensive update review.

Garlic (Allium sativum, Liliaceae) is used widely as a spice and medicinal herb not only in its native region (Central Asia and northeastern Iran) but also all around the world. Garlic has abundance chemical compounds such as allicin, alliin, S-allyl cysteines, thiacremonone, diallyl-disulfide, diallylsulfide, and others. This medicinal plant and its constituents offer a lot of benefits including free-radical scavenging, anti-inflammatory, anticholesterolemic, anti-gastric ulcer, antimicrobial, anticancer, and antioxidant properties. Garlic also modulates the activity of several metabolizing enzymes. This review summarizes various in vitro and animal studies on the protective effects of garlic against natural and chemical toxicities. It has been shown that garlic and its major components can ameliorate the toxicity of different agents in brain, kidney, blood, liver, embryo, spleen, pancreas, heart, reproductive system in part through radical scavenging, antioxidant effect, reducing lipid peroxidation, anti-inflammatory, chelating agent, cytoprotective activities, increase protein synthesis in damaged tissues, suppressing apoptosis, modulation of p53, phosphoinositide 3-kinase, Akt, nuclear factor (erythroid-derived 2)-like 2, antioxidant responsive element, p38 MAPK, inducible nitric oxide synthase, cyclooxygenase-2, cytosolic phospholipases A2, cleaved-caspase-9, cleaved-caspase-3 Bcl-2, Bcl-2-associated X, peroxisome proliferator-activated receptor gamma, NF-jB, nuclear factor-kappaB signaling pathways and cytochrome P450 enzymes. With controlled clinical trials, garlic may be introduced as a universal antidote or protective plant against many toxic agents.