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Research and Development for COVID-19 Vaccines
Published in Srijan Goswami, Chiranjeeb Dey, COVID-19 and SARS-CoV-2, 2022
Srijan Goswami, Ushmita Gupta Bakshi
Moderna vaccines. The basic ingredients include both active and inactive ingredients. Active ingredients consist of nucleoside modified mRNA encoding the viral spike(S) glycoprotein of SARS-CoV-2. The inactive agents are PEG2000-DMG: 1,2-dimyristoyl-rac-glycerol, methoxypolyethylene glycol, 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol, SM-102: heptadecan-9-yl 8-((2-hydroxyethyl) (6-oxo-6-(undecyloxy) hexyl) amino) octanoate, tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate, and sucrose (ModernaTX, Inc., 2021); Oxford Vaccine Group 2020, 2021) (Figure 10.6).
The COVID-19 pandemic and development of drugs and vaccinations
Published in Edward M. Rafalski, Ross M. Mullner, Healthcare Analytics, 2022
The details are provided below:Name: mRNA-1273Manufacturer: ModernaTX, Inc.Type of Vaccine: mRNANumber of Shots: 2 shots, 28 days (1 month) apart. Some immunocompromised people should get 3 shotsDose Volume: 0.5 mlHow Given: Shot in the muscle of the upper armFull List of Ingredients:Active ingredient: Nucleoside-modified mRNA encoding the viral spike (S) glycoprotein of SARS-CoV-2Inactive ingredients: PEG2000-DMG: 1,2-dimyristoyl-rac-glycerol, methoxypolyethylene glycol; 1,2-distearoyl-sn-glycero- 3-phosphocholine; Cholesterol; SM-102: heptadecan-9-yl 8-((2-hydroxyethyl) (6-oxo-6-(undecyloxy) hexyl) amino) octanoate; Tromethamine; Tromethamine hydrochloride; Acetic acid; Sodium acetate; Sucrose
The engineering challenges and opportunities when designing potent ionizable materials for the delivery of ribonucleic acids
Published in Expert Opinion on Drug Delivery, 2022
Yan Ming Anson Lau, Janice Pang, Grayson Tilstra, Julien Couture-Senécal, Omar F. Khan
The administration route chosen for LNPs can impact local distribution in tissues, altering the fate and efficacy of LNPs in vivo. Local therapeutic effects can be achieved via administration methods such as intradermal (i.d.), intramuscular (i.m.), and subcutaneous (s.c.) injections [21,22]. For vaccine applications, these injection methods can systemically prime responses since resident immune cells and recruited antigen presenting cells are located in the skin and muscle to internalize and process antigens encoded in the payload of LNPs [21,22]. Results from human trials of i.m. and i.d. injections using ionizable lipids such as ALC-0315 and SM-102 revealed robust immune responses that are well tolerated [23–27]. The use of ALC-0315 in COVID-19 mRNA vaccines resulted in biodistribution mainly at the injection site after i.m. administration [28]. In contrast, when ALC-0315 was deployed i.v. in mice to deliver siRNA, functional delivery to the liver was observed [29]. In both studies, the ratios of ALC-0315, phospholipid, cholesterol, and PEG-lipid within the LNP remained constant.
Advances in mRNA-based drug discovery in cancer immunotherapy
Published in Expert Opinion on Drug Discovery, 2022
Claudia Augusta Di Trani, Myriam Fernandez-Sendin, Assunta Cirella, Aina Segués, Irene Olivera, Elixabet Bolaños, Ignacio Melero, Pedro Berraondo
In addition to electroporation, numerous non-viral vectors such as cationic nanoemulsions, liposomes, polyplexes, or polypeptidic-based systems have been evaluated for RNA delivery [18]. Among these methods, lipid nanoparticles led to the first regulatory approval of mRNA-based nanomedicines: the mRNA COVID-19 vaccines [19,20]. Lipid nanoparticles are composed of cholesterol, phospholipids, a polyethylene glycol-conjugated lipid, and an ionizable cationic lipid. The advantage of employing cationic lipids is that they maintain the nanoparticle neutral in electrostatic charge at physiological pH whereas they undergo protonation at the acidic pH of the endosome following endocytosis. Ionization in the endosome leads to its disruption and the release of the vesicle cargo into the cytoplasm. This process is called the ‘proton sponge effect’ and there are studies that propose that many other mechanisms could be involved in mRNA cytosolic release [21,22]. The cationic lipids used in the COVID-19 vaccines are SM-102 in the case of the Moderna vaccine and ALC-0315 in the Pfizer/BioNtech vaccine [23]. Delivery vectors can be optimized to provide tissue- or cell-specific expression, expanding the safety and efficacy of mRNA-based immunotherapy [24].
Can nanotechnology help in the fight against COVID-19?
Published in Expert Review of Anti-infective Therapy, 2020
Gabriela Palestino, Ileana García-Silva, Omar González-Ortega, Sergio Rosales-Mendoza
Liposome-based vaccines targeting coronaviruses is another approach for nanovaccine development. A liposome vaccine candidate was reported, targeting the non-structural polyprotein 1a (pp1a); with the ability to induce in mice the expansion of IFN-γ-producing CD8 + T cells and in vivo killing activities after s.c. immunization; moreover, the expanded CTLs were able to kill cells expressing naturally processed pp1a-derived peptides [89]. A similar approach was implemented for the N protein peptides, which led to the successful induction of CTLs responses in mice; mediating the in vivo clearance of vaccinia virus expressing epitopes of SARS-CoV [90]. Challenge studies to determine immunoprotection against the coronavirus itself remain as pending objectives. Interestingly, liposome-based complexes have also been applied for immunization aiming to generate monoclonal antibodies against MERS-CoV [91,92]. It is worth mentioning that at least one of the prominent vaccines under development against SARS-CoV-2 is based on liposomes that contain an mRNA encoding for the prefusion stabilized spike protein 2019-nCoV (mRNA-1273). The formulation contains an ionizable lipid, SM-102, and 3 commercially available lipids: cholesterol, DSPC, and PEG2000 DMG [93].