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Virus-like particles (VLPs) are a versatile, safe, and highly immunogenic vaccine platform. The use of a very flexible vaccine platform in COVID-19 vaccine development is an important feature that cannot be ignored. Incorporating the spike protein and its variations into VLP vaccines is a desirable strategy as the morphology and size of VLPs allows for better presentation of several different antigens.
Name | Platform | Adjuvant | Dosage | Efficacy * | References |
---|---|---|---|---|---|
Coronavac (Sinovac) |
Inactivated | Alum | 2 doses | 83.5% (95% CI, 65.4–92.1) | [8][9][10][11] |
BBIBP-CorV (Sinopharm) |
Inactivated | Alum | 2 doses | 72.8% (95% CI, 58.1–82.4) | [12][13] |
BBV152-Covaxin (Bharat Biotech) |
Inactivated | Alum | 2 doses | 77.8% (95% CI, 65.2–86.4) | [14][15] |
AZD1222–Vaxzevria (Oxford/AstraZeneca) |
Viral vector | No | 2 doses | 74.0% (95% CI, 65.3–80.5) | [16][17][18] |
Covishield (Oxford/AstraZeneca formulation) |
Viral vector | No | 2 doses | 74.0% (95% CI, 65.3–80.5) | [16][17][18] |
Ad26.COV2.S (Johnson &Johnson-Janssen) |
Viral vector | No | 1 dose | 66.9% (95% CI, 59.0–73.4) | [19][20][21][22] |
mRNA-1273 (Moderna) |
mRNA | No | 2 doses | 94.1% (95% CI, 89.3–96.8) | [23][24] |
BNT162b-Comirnaty (Pfizer/BioNTech) |
mRNA | No | 2 doses | 95% (95% CI, 90.3–97.6) | [25][26] |
Some studies have shown that the minimal requirement for the assembly of SARS-CoV-2 VLPs and other coronaviruses is the combination of M and either the E or N proteins. However, most particles include the N protein and the highly immunogenic S protein for better assembly and expression (Figure 5A) [74][75]. To date, Vero E6 cells presented the highest expression of S-containing VLPs when compared to HEK293 cells [75]. All of these initial approaches for SARS-CoV-2 VLP production show a promising use of this platform in vaccine development. However, industrial viability and large-scale production were not considered, and these are crucial features for further development and are still very challenging in the eVLP production field [58].
Although homologous VLPs are an attractive strategy for producing these particles, the combination of antigenic SARS-CoV-2 proteins with other highly expressed heterologous proteins (that could be used as alternative VLPs scaffolds) are an exciting strategy to address issues of industrial production. The NDVLP-S2P (Figure 5B) is a heterologous chimeric eVLP vaccine candidate against SARS-CoV-2 that uses the structure of a well-characterized enveloped virus, the Newcastle disease virus (NDV) [41], and is being developed by the National Institute of Allergy and Infectious Diseases (NIAID). The transmembrane domain of the NDV fusion protein was fused to SARS-CoV-2 S2P, allowing the correct display of S2P on the VLP surface [41][45][76]. The NDV-S2P VLPs were more immunogenic than the trimeric S protein alone, showing that the presentation of antigens on the surface of the VLPs is advantageous [41]. Another heterologous SARS-CoV-2 eVLPs vaccine candidate is the CoVLP from Medicago/GSK (Figure 5C) [37][77]. This vaccine is based on VLPs that display a mutated S2P protein, which comprises a plant signal peptide, GSAS substitutions in the S1/S2 site, and TM/CD regions of the Influenza H5 A/Indonesia/5/2005. The CoVLP vaccine is formulated with AS03 [78] and given in a two-dose regimen. After the second dose, immunized volunteers showed higher serum SARS-CoV-2 nAb titers than in convalescent plasma. This vaccine candidate is already in phase 3 clinical trials (NCT04636697). VBI-2902a [76] is an MLV-based eVLPs vaccine candidate containing the S protein in the prefusion state fused with the VSV-G transmembrane cytoplasmic domain (VSV-GTC) (Figure 5D). This vaccine is being developed by VBI Vaccines and is in ongoing clinical trials 1/2 (NCT04773665).
Figure 5. Enveloped and nonenveloped VLPs against SARS-CoV-2.
Unlike eVLPs, neVLPs do not contain any lipid membranes. They can be produced in simpler expression systems, such as those using bacteria (i.e., Escherichia coli) and yeast (i.e., Saccharomyces cerevisiae and Pichia Pastoris) cells. The Hepatitis B virus vaccine, Engerix-B® [79], and the Human papillomavirus vaccine, Gardasil® and Gardasil 9® [33], are neVLPs-based vaccines approved by the FDA. They are produced in Saccharomyces cerevisiae, an efficient expression system that is industrially scalable and cheaper than mammalian and insect cell systems. Despite these clear advantages, bacteria and yeast cells lack complex post-translational modifications (PTM) needed to produce some proteins, such as the highly glycosylated SARS-CoV-2 S protein [80][81]. Thus, the choice of the best expression system could be a determinant for protein/VLP production, even considering neVLPs. Cervarix® is another HPV neVLP-based vaccine [82] that is highly immunogenic [83] and effective [84][85] against HPV types 16 and 18, which are the main serotypes that cause cervical cancer [86]. The Cervarix® vaccine is produced using insect cells infected with recombinant baculovirus [40][87][88].