. 2021 Dec 14;22(24):13445. doi: 10.3390/ijms222413445

Table 1.

Summary of advances in protein nanoparticle vaccines for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Nanoparticle	Immunogen	In Vivo Model	Adjuvant	Route	Dose (μg)	Infection	Ref.
Ferritin (Bullfrog and Helicobacter pylori)	S protein RBD protein RBD protein and N-terminal domain	BALB/c mouse C57BL/6 mouse K18-hACE2 mouse	ALFQ or Alhydrogel	Intramuscular	0.08–10	Intranasal (1.25 × 10⁴ PFU)	[13]
	S protein	C57BL/6 mouse	ALFQ or Alhydrogel	Intramuscular	10	N/A	[50]
	S protein	Rhesus macaque	ALFQ	Intramuscular	5–50	Intranasal and Intratracheal (1.00 × 10⁶ TCID50)	[51]
	RBD protein	Ferret	AddaVax	Intramuscular	15	Intranasal (1.00 × 10⁵–1.00 × 10⁶ TCID50)	[7]
	RBD protein	Ferret	AddaVax	Intramuscular and Intranasal	15	Intranasal (1.00 × 10⁵–1.00 × 10⁶ TCID50)	[7]
Ferritin (Helicobacter pylori)	RBD protein	Cynomol gusmacaque	3M-052 and Alhydrogel	Intramuscular	100	Intranasal and Intratracheal (1.00 × 10⁵ PFU)	[52]
Ferritin (Helicobacter pylori)	RBD protein	Rhesus macaque	3M-052 and Alhydrogel	Intramuscular	100	Intranasal and Intratracheal (1.00 × 10⁵ PFU)	[52]
	RBD protein and HR domain	BALB/c mouse	Sigma Adjuvant System	Subcutaneous	10	Intranasal (4.00 × 10⁴ FFU)	[35]
		C57BL/6 mouse(hACE2 transgenic)		Subcutaneous	10
		Rhesus macaque		Intramuscular	50
	S protein	C57BL/6 mouse	Sigma Adjuvant System	Subcutaneous	20	N/A	[53]
	S protein	Syrian golden hamster	Sigma Adjuvant System	Intramuscular	100	Intranasal (1.99 × 10⁴ TCID50)	[53]
	S protein	BALB/c mouse	Quil-A and MPLA	Subcutaneous	0.1–20	N/A	[48]
Ferritin (Pyrococcus furiosus)	RBD protein	C57BL/6 mouse	CpG 1826	Subcutaneous	12.3–30.7	N/A	[54]
I53-50 (Artificial)	S protein	BALB/c mouse	Poly(I:C)	Subcutaneous	13	N/A	[55]
		New Zealand white rabbit	Squalene emulsion	Intramuscular	39	N/A
		Cynomolgus macaque	MPLA liposome	Intramuscular	50	Intranasal and Intratracheal (1.00 × 10⁶ PFU)
	RBD protein	BALB/c mouse	AddaVax	Intramuscular	0.9–5	Intranasal (1.00 × 10⁵ PFU)	[56]
	RBD protein	Kymab Darwin mouse	AddaVax	Intramuscular	0.9–5	N/A	[56]
Mi3 (Artificial)	RBD protein (4a, 4b, or 8)	BALB/c mouse	AddaVax	Intraperitoneal	5	N/A	[57]
MS2 (Emesvirus zinderi)	S protein	Syrian golden hamster	Alhydrogel	Subcutaneous	60	Intranasal (1.00 × 10³ PFU)	[58]
Dps (Sulfolobus islandicus)	RBD protein	C57BL/6J mouse	CpG 1668	Subcutaneous	25–50	N/A	[59]
	RBD protein	K18 mouse (hACE2 transgenic)			25	Intranasal (1.00 × 10⁴ PFU)
	S protein	C57BL/6J mouse			25–50	N/A
	Nucleocapsid protein	C57BL/6J mouse			25–50	N/A
I3-01v9 (Artificial)	S protein	BALB/c mouse	AddaVax or Adju-Phos	Intraperitoneal	50	N/A	[60]
E2p (Geobacillus sterothermophilus)	S protein
Ferritin (Helicobacter pylori)	S protein
Ferritin (Helicobacter pylori)	RBD protein
Bann (Tomato bushystunt virus)	RBD protein	BALB/c mouse	N/A	Intramuscular, Intranasal, or Sublingual	20 (Plasmid)	Intranasal (70 μL of VSV-S pseudovirus)	[61]
Bann (Tomato bushystunt virus)			AddaVax	Intramuscular	100 (protein)
Foldon (T4 bacteriophage fibritin)			N/A	Intramuscular	20 (Plasmid)
Ferritin (Bullfrog and Helicobacter pylori)			N/A	Intramuscular	20 (Plasmid)
AaLS (Aquifex aeolicus)			N/A	Intramuscular	20 (Plasmid)
I53-50 (Artificial)	RBD protein	BALB/c mouse	AddaVax or Sigma Adjuvant System	Subcutaneous	11.91	N/A	[20]
Mi3 (Artificial)					9.51
Ferritin (Helicobacter pylori)					9.34

Abbreviations: ALFQ, army liposome formulation containing QS-21; COVID-19, coronavirus disease 2019; PFU, plaque-forming units; RBD, receptor-binding domain; Th1, T helper 1 cells; APC, antigen-presenting cells; TCID50, tissue culture infectious dose 50; HR, heptad repeat; hACE2, human angiotensin-converting enzyme 2; MPLA, monophosphoryl lipid A; sgRNA, subgenomic RNA; 4a, (SARS-CoV-2, SHC014, RaTG13, Rs4081); 4b, (pang17, RmYN02, Rf1, WIV1); 8, (4a and 4b).