A Comparison of Plasmid DNA and mRNA as Vaccine Technologies
Abstract
:1. Introduction
2. Background
3. mRNA Structure and Implications for Use as a Vaccine
4. Manufacture
5. Stability as a Product
6. Cellular Targets for mRNA and Plasmid DNA Vaccine Delivery
7. Increasing the Potency of DNA and mRNA Vaccines
7.1. Self-Amplifying Systems for Both mRNA and DNA Vaccines
8. Inflammatory Responses and Toxicities
8.1. Immune Activation
8.2. Toxicities of mRNA
9. Other Potential Safety Issues
10. Clinical Trials
10.1. DNA
10.1.1. Licensed Veterinary DNA Vaccines
10.1.2. Significance of Licensed Veterinary DNA Vaccines for Human DNA Vaccines
10.1.3. Select Human DNA Vaccine Clinical Trials Results
10.1.4. Additional Categories of Disease Targets for DNA Vaccines and Methods to Increase Efficacy
10.2. RNA
10.2.1. Prophylactic mRNA Vaccines for Infectious Diseases
10.2.2. Additional Clinical Trials of RNA
RNA as an Adjuvant
Immunotherapeutic Vaccine
Immunoprophylaxis via Provision of mRNA Encoding a Monoclonal Antibody
Cancer
11. Summary and Conclusions
Funding
Conflicts of Interest
References
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Product, Company/Institution | Indication (disease) | Antigen | Formulation | Phase | Status | Results | National Clinical Trial Identifier |
---|---|---|---|---|---|---|---|
RNActive® CureVac | Rabies | Rabies virus glycoprotein [55] | None | 1 | Active, Not Recruiting | Generally safe, but some significant adverse events (AEs); boostable functional antibodies | NCT02241135 |
RNActive® CureVac | Rabies | Rabies virus glycoprotein | None | 1 | Recruiting | New construct versus prior trial | NCT03713086 |
mRNA-1851 Moderna | Influenza H7N9 | Influenza Hemagglutinin H7N9 A/Anhui/1/2013 [94] | Lipid Nano-particles | 1 | Active, Not Recruiting | Moderna website says 1° and 2° endpoints met, but no published data | NCT03345043 |
mRNA-1440 Moderna | Influenza H10N8 | Influenza Hemagglutinin H10N8 (A/Jiangxi-Donghu/346/2013) [94] | Lipid Nano-particles | 1 | Active, Not Recruiting | Interim: AEs: Majority mild moderate; A few: severe; Seroconversion rates high | NCT03076385 |
mRNA-1653 Moderna | Human Metapneumo-virus + Parainfluenza virus 3 | Fusion proteins of each virus | Lipid Nano-particle | 1 | Active, Not Recruiting | Announced via press release safe and immunogenic; no publications found | NCT03392389 |
mRNA-1388 Moderna/DARPA | Chikungunya | Not Disclosed (ND) | ND | 1 | Active, Not Recruiting | Primary Completion: March 2019; no results posted at time of publication | NCT03325075 |
RNA-1325 Moderna/BARDA | Zika | prM and E [95,96] | Lipid Nano-particles | 1 | Active, Not Recruiting | Primary Completion: February 2019; no results posted at time of publication | NCT03014089 |
mRNA-1647 and mRNA-1443 Moderna | Cytomegalovirus | mRNA-1647 is gB, pentameric complex, and mRNA-1443 is pp65 [97] | Lipid Nano-particles | 1 | Recruiting | Primary Completion: February 2020 | NCT03382405 |
mRNA-1777 Moderna/Merck-V171 | Respiratory Syncytial Virus | ND | ND | 1 | ND | Moderna press release says 1° and 2° endpoints met, but no published data | Not listed on clinicaltrials.gov |
RNA-based Adjuvant: long-chain non-coding RNA complexed with a short cationic peptide (ssRNA adjuvant); no mRNA-encoded antigen
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Liu, M.A. A Comparison of Plasmid DNA and mRNA as Vaccine Technologies. Vaccines 2019, 7, 37. https://doi.org/10.3390/vaccines7020037
Liu MA. A Comparison of Plasmid DNA and mRNA as Vaccine Technologies. Vaccines. 2019; 7(2):37. https://doi.org/10.3390/vaccines7020037
Chicago/Turabian StyleLiu, Margaret A. 2019. "A Comparison of Plasmid DNA and mRNA as Vaccine Technologies" Vaccines 7, no. 2: 37. https://doi.org/10.3390/vaccines7020037