Table 1.

Vaccine development platforms against SARS-CoV-2, their viral targets, manufacturing description, advantages, and disadvantages.

(A) Vaccine Type	(B) Target	(C) Description	(D) Advantages	(E) Limitations
Live attenuated	Whole virus	Live viruses are weakened to reduce virulence, selected by growth in heterologous species and/or in tissue culture cells.	Induction of strong B and T cell responses	Risk for infection remains due to genetic reversion. They can cause disease in immune compromised individuals.
			Single administration without adjuvant is sufficient to induce protective immunity	Storage at cooler temps
			Often confers long-term immunity
Inactivated whole virus	Whole virus	Whole virus is inactivated by chemical or physical procedures.	Risk of infectivity is eliminated without destroying antigenicity	Booster(s) may be required thus increasing cost
		Often administered with adjuvants.	Vaccine is stable.	Use of adjuvants may cause unwanted inflammatory response.
			Safe as no live virus is present.
Subunit	S protein	Made of specific viral proteins or groups of proteins. Can be purified directly from viral particles.	Safe as viral particles cannot induce infection.	Induce insufficient cellular immunity.
			Viral proteins chosen likely to be immunogenic, inducing protecting antibodies,	Immune responses become weaker over time.
				Booster shots may be necessary thus increasing the cost of vaccination.
VLP-based (Subunit)	S protein	Viral surface antigens naturally occurring or synthesized are self-assembled into VLPs.	Present antigens in a dense, repetitive manner, enabling the cross-linking of B cell receptors.	Risk of presence of host cell-derived particles.
			Stimulate protective neutralizing antibodies.	Challenges to produce VLPs with optimal quality, stability, and good immunogenicity at high yield.
			Self-adjuvating properties.
			Safe because VLPs do not induce infection.
Vector-based	S protein	Gene encoding a major viral antigen is inserted (cloned) into another, non-virulent viral vector expressing introduced protein.	Long term gene expression.	Large-scale manufacturing of viral vectors may be expensive.
			Stimulates both humoral and cellular immune responses against introduced antigen.	Recombinant viruses may cause disease in immunocompromised hosts.
				Pre-existing antibodies to the vector may misdirect immune responses to vaccinating antigen.
DNA-based	S protein	Genetically engineered plasmids containing DNA for viral antigens.	Rapid production capacity.	Weaker induction of immunity.
		Relies on in situ production of the target antigen.	Induction of B and T cell responses.	Risk for integration into recipient’s chromosomal DNA resulting insertional mutagenesis.
			Long shelf life.	Require specific delivery devices which increases cost of administration.
			Heat stable as compared to RNA vaccine.
			Inexpensive to produce.
			No risk of infection.
RNA-based	S protein	RNA sequence for viral antigens administered by carriers such as lipid nanoparticles.	Stimulates both cellular and humoral immunity.	Encoding only some fragments instead of whole virus limiting its immunogenicity.
			Direct delivery into the cytosol may enhance antigen expression.	Lack of interaction with endosomal RNA receptors may weaken immunostimulation.
			May be designed to be self-adjuvating.	Necessity to keep at cooler temperatures.
			Less likely to cause adverse effects such as allergies.	Vaccine delivery and uptake challenging in vivo.
			Does not interact with the genome.
			Rapid production capacity.