Table 2.
SARS-CoV-2 Vaccine Development Platforms
| Platform (Refs) |
No. Clinical Trials | No. Pre-clinical Studies | Platform Status | Advantages | Disadvantages | Existing Licensed Vaccines |
|---|---|---|---|---|---|---|
| Inactivated | 5 | 9 | Licensed | Safety: • Cannot replicate |
Safety: • Infection risk |
HAV, influenza (shot only), Polio (shot only), rabies |
| • No adjuvants required | ||||||
| Efficacy: • High potency • Multivalent |
Efficacy: • Often induces weaker immune responses than other methods |
|||||
| Production and Manufacturing: • Complex manufacturing—lengthy, relatively small quantities produced | ||||||
| • Requires vigorous quality control | ||||||
| Live attenuated virus | 0 | 3 | Licensed | Safety: • No adjuvants required |
Safety: • Reversion risk |
Measles, mumps, rubella (MMR combined vaccine), rotavirus, smallpox, chickenpox, yellow fever |
| • Inactivation may lead to undesired effects and exacerbated disease | ||||||
| • Adverse effects in immune-compromised | ||||||
| Efficacy: • High potency • Multivalent • Induction of long-lived responses |
Efficacy: • Inactivation may hamper protective immune responses |
|||||
| Production and Manufacturing: • Requires whole pathogen cultivation, high biosafety level, and specialized laboratories | ||||||
| • Relatively high production costs requires dedicated production processes and facilities for each vaccine | ||||||
| • Insufficient production capacities for global vaccination | ||||||
| Viral vector | Non-replicating: 5 Replicating: 1 |
Non- replicating: 19 Replicating: 17 |
Experimental | Safety: • Favorable safety profile—whole pathogen cultivation not required • No adjuvants required |
Safety: • Potential induction of anti-vector immunity |
Non-replicating: none Replicating: dengue fever |
| • Potential environmental risks associated with the release of genetically modified organisms | ||||||
| • Potential integration into the host genome and persistent replication of attenuated vaccines | ||||||
| • Potential risk for infection | ||||||
| Efficacy: • Previous infection/pre-existing immunity to the viral vector may hamper immune responses | ||||||
| • Inability to administer multiple times | ||||||
| Production and Manufacturing: • Cell-based and antigen-dependent manufacturing | ||||||
| • Requires vigorous monitoring | ||||||
| • Complex manufacturing | ||||||
| Efficacy: • Able to induce potent, antigen-specific cellular and humoral immune responses |
||||||
| • Strong innate immune response | ||||||
| Production and manufacturing: • High producibility—independent of whole pathogen cultivation | ||||||
| • High specificity and accuracy—can be engineered easily to accurately express any antigen of choice, specific targeting, and processing in the cell due to antigen delivery as genetic information | ||||||
| • High versatility—allows large insertions in genome and therefore the development of a large variety of vaccines | ||||||
| • Sufficient production capacities for global vaccination due to established high yield production processes with means of upscaling | ||||||
| Protein Subunit | 7 | 50 | Licensed | Safety: • Non-infectious |
Safety: • Requires additional adjuvants |
Hib, HBV, HPV, Whooping cough (part of the DTaP combined vaccine), Pneumococcal disease, Meningococcal disease, Shingles |
| Efficacy: • Strong humoral response |
Efficacy: • Multiple doses are usually required |
|||||
| Production and Manufacturing: • Requires dedicated production processes, facilities and stability assays for each vaccine | ||||||
| • Multivalent formulation can be challenging | ||||||
| RNA | 6 | 16 | Experimental | Safety: • Favorable safety profile—whole pathogen cultivation not required, non-infectious |
Safety: • Potential risk for severe adverse reactions |
None |
| • No interaction with the host-cell DNA, avoiding the potential risk of genomic integration | ||||||
| • Natural degradation and lack of persistence in cells | ||||||
| Efficacy: • Generation of potent humoral and cellular immune responses | ||||||
| • Very potent innate immune response | ||||||
| • Can be administered multiple times (boosting) | ||||||
| Administration: • Can be administered by different routes, do not require additional administration devices | ||||||
| Production and Manufacturing: • High specificity—able to encode any antigen of choice |
• Production and Manufacturing: • Relatively high production costs |
|||||
| • High versatility—able to produce different vaccines using the same established production process and facility. | ||||||
| • Safe, rapid, and scalable production—based on in vitro systems that are simple to monitor, production free of animal-derived products | ||||||
| • Small amounts of expressed protein required due to amplification by the immune system | ||||||
| DNA | 4 | 12 | Experimental | Safety: • Favorable safety profile— whole pathogen cultivation not required, non-infectious |
Safety: • Potential long-term persistence, risk of genomic integration, potentially leading to mutagenesis and oncogenesis. |
None |
| • Potential generation of autoantibodies | ||||||
| • Potential adverse effects due to cytokines/co-stimulatory molecules expression used to enhance DNA immunogenicity | ||||||
| Efficacy: • Generation of potent humoral and cellular immune responses |
Efficacy: • Low immunogenicity in humans |
|||||
| • High stability | ||||||
| Production and Manufacturing: • High specificity—able to encode any antigen of choice |
Production and Manufacturing: • Requires additional methods to enhance DNA uptake, expression, and immunogenicity: delivery devices such as gene gun, needle, jet injection, and in vivo electroporation and molecular adjuvants |
|||||
| • Safe, rapid and scalable production—based on in vitro systems that are simple to monitor, production free of animal-derived products | ||||||
| Other platforms | 1 | 12 | N/A | N/A | N/A | N/A |
DNA, Deoxyribonucleic acid; DTaP, diphtheria, tetanus, and acellular pertussis; HAV, Hepatitis A virus; Hib, Haemophilus influenzae type b; HBV, Hepatitis B virus; HPV, human papillomavirus; RNA, ribonucleic acid.