Nanomaterial Delivery Systems for mRNA Vaccines
Abstract
:1. Introduction
2. Early Delivery Systems for mRNA Vaccines
3. Polymers for mRNA Delivery
4. Development of Lipid Nanoparticles for the Current SARS-CoV-2 Clinical Trials
5. mRNA Lipid Nanoparticles in the Current SARS-CoV-2 Clinical Trials
5.1. BioNTech/Pfizer
5.2. Moderna
5.3. CureVac
5.4. TranslateBio
5.5. Arcturus
5.6. Imperial College London
5.7. Chulalongkorn University, University of Pennsylvania
5.8. Providence Therapeutics
5.9. Storage and Distribution
6. Lipidoid Nanoparticles
7. Intranasal Delivery of mRNA Lipid Nanoparticles
8. Delivery of mRNA LNPs Encoding Antibodies
9. Assembly and Structure of Lipid Nanoparticles
10. Determinants of Performance of mRNA Delivery Systems for Vaccines
10.1. Dose
10.2. Potency and Delivery Efficiency
10.3. Endosomal Release
10.4. Charge and Ligand Mediated Targeting
10.5. Adjuvanticity of the Lipid Nanoparticle
10.6. Injection Site Reactions, Safety, Tolerability, Reactogenicity of mRNA LNPs
11. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Company | mRNA Type | Immunogen | mRNA Dose (µg) | Confirmed or Probable LNP Class | Publications |
---|---|---|---|---|---|
Moderna | nucleoside modified mRNA | membrane bound prefusion stabilized spike | 100 | Lipid H [42] confirmed in [41] | [43,44,45,46] |
BioNTech Pfizer | nucleoside modified mRNA | membrane bound prefusion stabilized spike | 30 | Acuitas ALC-0315 [47] confirmed in [40] | [48,49,50,51] |
CureVac | unmodified mRNA | membrane bound prefusion stabilized spike | 12 | Acuitas ALC-0315 [47] | [52,53] |
TranslateBio Sanofi | unmodified mRNA | prefusion stabilized double mutant spike | 7.5 | ICE [54] or Cysteine [55] | [56] |
Arcturus | self-amplifying mRNA | full length spike | 1–10 | Lipid 2,2 (8,8) 4C CH3 [57] | [58] |
Imperial College | self-amplifying mRNA | membrane bound prefusion stabilized spike | 1–10 | Acuitas A9 [59] | [60] |
Chulalongkorn | nucleoside modified mRNA | secreted wild type spike | Not available | Genevant CL1 [61] | NA |
Name | Ionizable Lipid Structure and Theoretical pKas | TNS pKa |
---|---|---|
MC3 [92] | 6.4 | |
Lipid 319 [68] | 6.38 | |
C12-200 [103] | 6.96 | |
5A2-SC8 [104] | 6.67 | |
306Oi10 [105] | 6.4 | |
Moderna Lipid 5 [101] | 6.56 | |
Moderna Lipid H, SM-102 [42] | 6.75 | |
Acuitas A9 [59] | 6.27 | |
Acuitas ALC-0315 [47] | 6.09 | |
Arcturus Lipid 2,2 (8,8) 4C CH3 [57] | 6.69 | |
Genevant CL1[61] | NA |
Delivery System | mRNA Type | Species | Dose | Readout | Reference |
---|---|---|---|---|---|
Naked mRNA | non-modified | mouse | 80 µg twice | protection | [140] |
Naked mRNA | self-amplifying | mouse | 1.25 µg twice | protection | [140] |
Protamine | non-modified | mouse | 10 µg twice | neutralizing titers | [66] |
Protamine | non-modified | mouse | 80 µg twice | protection | [66] |
Modified Dendrimer | self-amplifying | mouse | 40 µg once or 4 µg twice | neutralizing titers | [126] |
DOTAP/DOPE/PEG | nucleoside modified | mouse | 12 µg twice intranasal | neutralizing titers and protection | [130] |
Cationic Nanoemulsion | self-amplifying | mouse | 15 µg twice | neutralizing titers | [70] |
Nanostructured Lipid Carrier | self-amplifying | mouse | 0.1 µg once | neutralizing titers | [71] |
LNP (Acuitas) | non-modified | mouse | 0.5 µg twice | neutralizing titer | [69] |
LNP (MC3) | nucleoside-modified | mouse | 10 µg once or 2 µg twice | protection | [99] |
LNP (MC3) | nucleoside-modified | mouse | 0.4 µg once | protection | [97] |
LNP (Acuitas) | nucleoside-modified | mouse | 0.5 µg once | protection | [141] |
LNP (Acuitas) | nucleoside-modified | mouse | 1 µg twice | neutralizing titers | [49] |
LNP (Moderna) | nucleoside-modified | mouse | 1 µg twice | neutralizing titers and protection | [45] |
LNP (Acuitas) | non-modified | mouse | 0.25 µg twice | neutralizing titers | [53] |
LNP (Translate Bio) | non-modified | mouse | 0.2 µg twice | neutralizing titers | [56] |
LNP (Arcturus) | self-amplifying | mouse | 2 µg once | neutralizing titers and protection | [58] |
LNP (Acuitas) | self-amplifying | mouse | 0.1 µg twice | neutralizing titers | [60] |
LNP (Acuitas) | non-modified | Syrian Hamster | 10 µg twice | protection | [53] |
LNP (MC3) | nucleoside-modified | ferret | 50 µg once | neutralizing titers | [97] |
Cationic Nanoemulsion | self-amplifying | non-human primate | 75 µg twice | neutralizing titers | [70] |
LNP (MC3) | nucleoside-modified | non-human primate | 200 µg twice | neutralizing titers | [97] |
LNP (MC3 or Moderna Lipid H) | nucleoside-modified | non-human primate | 5 µg twice | neutralizing titers | [42] |
LNP (Acuitas) | nucleoside-modified | non-human primate | 30 µg twice | neutralizing titers | [49] |
LNP (Moderna) | nucleoside-modified | non-human primate | 100 µg twice | neutralizing titers | [45] |
LNP (Translate Bio) | non-modified | non-human primate | 15 µg twice | neutralizing titers | [56] |
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Buschmann, M.D.; Carrasco, M.J.; Alishetty, S.; Paige, M.; Alameh, M.G.; Weissman, D. Nanomaterial Delivery Systems for mRNA Vaccines. Vaccines 2021, 9, 65. https://doi.org/10.3390/vaccines9010065
Buschmann MD, Carrasco MJ, Alishetty S, Paige M, Alameh MG, Weissman D. Nanomaterial Delivery Systems for mRNA Vaccines. Vaccines. 2021; 9(1):65. https://doi.org/10.3390/vaccines9010065
Chicago/Turabian StyleBuschmann, Michael D., Manuel J. Carrasco, Suman Alishetty, Mikell Paige, Mohamad Gabriel Alameh, and Drew Weissman. 2021. "Nanomaterial Delivery Systems for mRNA Vaccines" Vaccines 9, no. 1: 65. https://doi.org/10.3390/vaccines9010065
APA StyleBuschmann, M. D., Carrasco, M. J., Alishetty, S., Paige, M., Alameh, M. G., & Weissman, D. (2021). Nanomaterial Delivery Systems for mRNA Vaccines. Vaccines, 9(1), 65. https://doi.org/10.3390/vaccines9010065