12. Virus- like particle (VLP) vaccines
VLPs are a group of synthetic or unprompted non-infectious viral like structures that containing prominent structural viral proteins without genetic materials (Fig. 2) (Table 3). This technology has been applying in vaccines against several viral pathogens such as HBV and HPV [113]. In relation to coronavirus infections, VLPs are formed in infected eukaryotic cells by active germination and contain E, M, S and possibly N proteins without the presence of encoding RNA genome [114]. The VLP containing S protein, like infectious viral particles, forays ACE2-expressing cells, but conversely elicit antibody responses by cross-linking the surface B cell receptors [115]. However, the VLP vaccines, like inactivated and subunit vaccines, require adjuvants and booster doses [116]. These can either be caused by in vivo viral vector replication like MVA which expressed VLP crucial protein components or produced in vitro by VLP target cells. The well-defined efficacy of VLP-based vaccines together with the known biology and safety of coronavirus VLPs, pave the way for the mass production and Good Manufacturing Practice requirements acquisition of emerging coronavirus VLP vaccines. Of the 20 VLP-based vaccines against COVID-19, only two including CoVLP by Medicago biotechnology company and RBD SARS-CoV-2 HBsAg VLP vaccine by Serum Institute of India and Accelagen Pty have arrived the clinical trials while the rest are completing the preclinical stages [52]. CoVLP is a plant derived candidate that mimics the wild-type virus without genetic material and involved both antibody and cell-mediated responses in preclinical testing. Currently in a research partnership between Medicago and Dynavax, as well as Medicago and GSK with or without CPG1018 and AS03 adjuvants respectively, the safety, efficacy and tolerability of CoVLP vaccine is being investigated in healthy adults [117]. Also, with the aim of better stimulating antibody responses, the scientists created conjugates of the SARS-CoV2 RBD domain and HBV surface antigen, RBD SARS-CoV-2 HBsAg VLP vaccine, that is undergoing phase Ι clinical evaluations [52]. Surprisingly, A Canadian pharmaceutical company was able to obtain the required VLP for SARS-CoV2 vaccine using genetically manipulated plants. The results of this study were not published, but apparently it was able to elicit significant antibody responses in mice [118].