Table 1. Overview of published preclinical in vivo studies of DNA vaccines against SARS-CoV-2.

Category	Animal model	Delivery route	Dose	Antigen	Immune responses	Ref.
Plasmid DNA	BALB/c mice, C57BL/6 mice, and guinea pigs	IM + EP for mice, ID + EP for guinea pigs	Twice (2.5, 10 or 25 μg) for mice, single (100 μg) for guinea pigs	S protein	H, C, nAb	[103]
Plasmid DNA	Rhesus macaques	IM	Twice (5 mg)	Different forms of the S protein: full length, deletion of the cytoplasmic tail, the soluble ectodomain, S1 domain with a foldon trimerization tag, RBD with a foldon trimerization tag, prefusion-stabilized soluble ectodomain with two proline mutations, deletion of the furin cleavage site and a foldon trimerization tag	H, C, nAb	[105]
Plasmid DNA	BALB/cJ mice	EP	Twice (60 μg)	Engineered RBD, with four novel glycosylation sites, fused to multimerization platforms	nAb	[106]
Plasmid DNA	Syrian hamsters	IM + jet injection	Single (0.2 mg)	S protein	nAb	[107]
Plasmid DNA	C57BL/6 and BALB/c mice	(IM or ID) + EP	Twice (days 1 and 14 or 21)	Prefusion-stabilized S protein/alone or combined with plasmid IL-12	nAb	[108]
Plasmid DNA	Rhesus macaques	Needle Free Injection System (NFIS)/Syringe-needle injection (ID)	Thrice (days 1, 28 and 56)	S protein	nAb	[109]
Plasmid DNA	C57BL/6 mice	IM	Thrice (weeks 0, 2 and 4)	RBD fused to the amino-terminal region of hepatitis B virus preS1 with a W4P mutation	H, C, nAb	[110]
Plasmid DNA	ICR mice	IM + EP	Thrice (weeks 0, 2 and 4)	S protein or S1 subunit or S2 subunit	H, C, nAb	[111]
Plasmid DNA+ recombinant protein	Rhesus macaques	IM	Thrice (weeks 0, 2 and 8)	S protein (Plasmid DNA) + S1 subunit (Recombinant protein)	nAb	[112]

C: Cellular immune response; EP: Electroporation; H: Humoral immune response; ID: Intradermal; IM: Intramuscular; nAb: Neutralizing antibody; RBD: Eeceptor-binding domain; S: Spike protein.