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].