TABLE 1.
Preliminary studies on VLP vaccine candidates targeting the SARS‐CoV. MERS‐CoV, and SARS‐CoV‐2
| Features | Target viruses | Expression systems | References |
|---|---|---|---|
| Peptide‐based nanoparticle displaying SARS‐CoV HRC1 B‐cell epitope induced neutralizing antibodies which inhibited virus infection in vitro | SARS‐CoV | E. coli | Pimentel et al. 59 |
| Micellular nanoparticles based on SARS‐CoV S protein adjuvanted with matrix M1 induced neutralizing antibodies against SARS‐CoV. | SARS‐CoV | BEVS | Coleman et al. 76 |
| VLP formed from chimeric SARS‐CoV S protein carrying IAV HA, coexpressed with IAV M1 protein, protected mice from lethal SARS‐CoV challenge. | SARS‐CoV | BEVS | Liu et al. 77 |
| Chimeric VLP formed from mouse hepatitis virus (MHV) E, M, N proteins and SARS‐CoV S protein protected mice from SARS‐CoV challenge but resulted in pulmonary immunopathology. | SARS‐CoV | Mammalian cell | Lokugamage et al. 78 ; Tseng et al. 79 |
| VLP based on SARS‐CoV N protein induced high level of cytotoxic T cell responses when coadministered with plasmids encoding SARS‐CoV N protein and XIAP. | SARS‐CoV | Mammalian cell | Azizi et al. 80 |
| Micellular nanoparticles based on MERS‐CoV S protein adjuvanted with matrix M1 induced neutralizing antibodies against MERS‐CoV in a dose‐dependent manner. | MERS‐CoV | BEVS | Coleman et al. 76 ; Coleman et al. 81 |
| VLP formed from chimeric MERS‐CoV S protein carrying IAV HA, coexpressed with IAV M1 protein, induced antibodies capable of neutralizing pseudovirus of MERS‐CoV when adjuvanted with alum/CpG. | MERS‐CoV | BEVS | Lan et al. 82 |
| VLP formed from MERS‐CoV S, E, and M proteins adjuvanted with alum induced virus‐neutralizing antibodies and Th1‐mediated immune responses in rhesus macaques. | MERS‐CoV | BEVS | Wang et al. 83 |
| MERS‐CoV RBD displayed on parvovirus VP2 VLP induced pseudovirus neutralizing antibodies. When adjuvanted with poly(I:C), the VLP induced both Th1 and Th2 cell‐mediated immune responses. | MERS‐CoV | BEVS | Wang et al. 84 |
| MERS‐CoV RBD fused to ferritin‐based nanoparticle induced antibodies which inhibit the interaction between MERS RBD and hDPP4 receptor in a competitive ELISA. | MERS‐CoV | E. coli | Kim et al. 85 |
| Transmembrane region‐truncated MERS‐CoV S protein (SΔTM) produced in silkworm larvae assembled into nanoparticle and was able to bind to hDPP4. MERS‐CoV VLP were prepare by surfactant treatment and mechanical extrusion from Bm5 cell coexpressing MERS‐CoV S, E, and M proteins. | MERS‐CoV | Silkworm larvae, silk moth cell line | Kato et al. 86 |
| Mice primed with recombinant adenovirus serotype 5 encoding MERS‐CoV S protein, followed by boosters with MERS‐CoV S protein‐based VLP induced neutralizing antibodies, Th1, and Th2 immune responses, protected mice against virus challenge. | MERS‐CoV | Mammalian cell, BEVS | Jung et al. 87 |
| Transchromosomic bovine immunized with inactivated virus or MERS‐CoV S‐based micellular VLP produced fully human polyclonal IgG capable of reducing viral load in mouse model to near or below limit of detection when administarted before or after virus infection. | MERS‐CoV | Mammalian cells, transchromosomic bovine | Luke et al. 88 |
| MERS‐CoV RBD chemically cross‐linked to PLGA nanoparticle encapsulating the cyclic diguanylate monophosphate protected mice against lethal MERS‐CoV challenge. | MERS‐CoV | BEVS | Lin et al. 89 |
| Single dose of VSV replicon vaccine carrying SARS‐CoV‐2 RBD fused to glycoprotein of RABV protected mice from SARS‐CoV‐2 challenge. | SARS‐CoV‐2 | Mammalian cells | Hennrich et al. 90 |
| SARS‐CoV‐2 RBD (mammalian expressed) conjugated to SpyCatcher003‐mi3 VLP (E. coli expressed) via SpyTag/SpyCatcher technology induced neutralizing antibodies in mice and pigs. | SARS‐CoV‐2 | Mammalian cell, E. coli | Tan et al. 57 |
|
SARS‐CoV‐2 RBM displayed on bacteriophage AP205 VLP induced SARS‐CoV‐2 neutralizing antibodies. |
SARS‐CoV‐2 | E. coli | Liu et al. 60 |
| SARS‐CoV‐2 RBM fused to immunologically optimized cucumber mosaic virus VLP (CuMVTT) induced neutralizing antibodies in rabbits and mice. | SARS‐CoV‐2 | E. coli | Mohsen et al. 53 |
| SARS‐CoV‐2 RBD produced in mammalian cell chemically cross‐linked to CuMVTT produced in E. coli induced neutralizing antibodies in mice. | SARS‐CoV‐2 | Mammalian cell, E. coli | Zha et al. 58 |
| Prefusion‐stabilized SARS‐CoV‐2 S protein ectodomain (S2P) displayed on Newcastle disease VLP induced higher neutralizing antibodies than soluble S2P in mice. | SARS‐CoV‐2 | Mammalian cell | Yang et al. 91 |
| VLPs formed from co‐expressing influenza M1 protein with SARS‐CoV‐2 S or S1 induced neutralizing antibodies which partially inhibited binding of SARS‐CoV‐2 RBD to hACE2. | SARS‐CoV‐2 | BEVS | Chu et al. 92 |
|
SARS‐CoV‐2 S, E, and M co‐expressed in HEK‐293 cells assembled into VLP mimicking the actual virus. |
SARS‐CoV‐2 | Mammalian cell | Swann et al. 93 |
| SARS‐CoV‐2 S, E, M, and N co‐expressed in HEK‐293 T and Vero E6 cells assembled into VLPs mimicking the actual virus. | SARS‐CoV‐2 | Mammalian cells | Xu et al. 94 |
| SARS‐CoV‐2 S, E, and M co‐expressed in Saccharomyces cerevisiae platform (D‐Crypt™) self‐assembled into VLP mimicking the actual virus. | SARS‐CoV‐2 | Yeast | Arora et al. 95 |
Abbreviations: E, envelope; HA, haemagglutinin; hACE2, human angiotensin converting enzyme 2; IAV, influenza A virus; M, membrane; M1, matrix 1 protein; N, nucleocapsid; PLGA, poly(lactic‐co‐glycolic acid); RBD, receptor‐binding domain; RBM, receptor‐binding motif; S, spike; VLP, virus‐like particle.