Table 2.

Advantages/disadvantages of each vaccine platform.

	Advantages	Disadvantages
DNA	No handling of infectious material Can be used in immunocompromised subjects Reasonable and enduring immune response, both humoral and cell-mediated No anti-plasmid immune responses allowing for effective boosting (reported by Inovio) Rapid and scalable manufacturing Long-term stability Options for multivalent formulation Oral formulation possible (Symvivo)	No approved DNA vaccines, along with real-world experience in the global population Variable mucosal immunity and other immune responses Some require special tools for delivery to the sub-dermal layer (Inovio) Potential risk for host cell genomic integration (though likely small for plasmids)
RNA	Rapid design and production No handling of infectious material No potential for insertional mutagenesis Strong early antiviral responses, both humoral and cell-mediated Options for multivalent formulation Scaling up to global-wide production appears feasible but not yet tested	No approved RNA vaccines, but some clinical testing for other viruses (rabies, influenza) Inflammatory reactions possible Most formulations require a cold chain for longevity and stability Ubiquitous ribonucleases require careful design with substituted nucleosides and skilled formulation of lipid nanoparticle carriers for effective delivery Boosting likely necessary to achieve robust and long-lasting immunity
Protein	No handling of infectious material Strong antibody responses Precedent for successful vaccines of this platform Viral protein complexes can be formulated to simulate virus patterning (VLPs)	Need for adjuvants Scale up of manufacturing can be challenging Potentially lacking correct glycan shield of native virus
Viral Vector (both replicating/non-replicating)	Years of experience in the gene therapy field studying safety, immune responses Strong antibody and cellular responses	Risk for chromosomal integration and oncogenesis Cannot be used in immunocompromised subjects Preexisting antibodies to some vectors possible Potential for inflammatory AEs Variable immunogenicity Significant manufacturing hurdles at scale
Live Virus (attenuated)	Proven technology Strong immune response Multivalent Simple formulation, not requiring adjuvants Proven track record for economical large-scale manufacturing	Requires dedicated biosafety level facilities Risk for attenuated virus to regain virulence Can be complicated to scale up manufacturing
Virus (inactivated)	Proven technology Strong immune response Multivalent Simple formulation, not requiring adjuvants	Requires dedicated biosafety level facilities Complicated to scale up manufacturing

This is by no means an exhaustive list of pros/cons. There exists an enormous challenge for bringing forward an ideal vaccine to treat SARS-CoV-2 infection.