4.1 Whole Cell Antigen
The elements of virus particles, including proteins, lipids, polysaccharides, nucleic acids, and other associated components, constitute whole cell antigens (WCA) (Zhang et al., 2020). The development of killed and live-attenuated vaccines present the whole cell antigens to elicit immune response (Minor et al., 2015). In this regard virus strains of SARS-CoV-2 have been successfully isolated by many institutions globally for development of killed or live-attenuated whole cell vaccine (Zhang et al., 2020). However, it is unavoidable to face more difficulties in quality control and consistency evaluation of such vaccines because of complex compositions antigens and such vaccines require stringent screening and testing for obtaining strains with certified safety (Marohn and Barry, 2013). For example, a mutation (Y6398H) has been introduced into the Orf1a/b polyprotein (p59/nsp14/ExoN) which completely attenuated the virulence of mouse coronavirus (MHV-A59) and MHV-A59 vaccine significantly reduced virus replication in mice at day five following intracerebral inoculation (Morse et al., 2020).