6.1 Whole virus vaccines
Whole virus vaccines, either killed or live-attenuated, have multiple antigenic components which potentially induce wide variety of immunologic effectors in the host against virus (Sharma et al., 2011). The reverse genetics mechanism is adopted to generate live attenuated CoV vaccines by deletion of key virulence factors. Such vaccines are immunologically highly efficient and exert wider cross protection which potentially induce mucosal, systemic, humoral, and cell mediated immunity upon immunization (Roper and Rehm, 2009; Enjuanes et al., 2008; Saif 2017; Schindewolf and Menachery 2019). The inherent immunogenicity and ability of whole virus vaccines to stimulate toll-like receptors (TLRs) like TLR 3, TLR 7/8, and TLR 9 is their major advantage (Chen et al., 2020). These vaccines are considered most efficient in primary vaccination of naive hosts followed by parenteral booster vaccines for better protection (Saif, 2017). This reverse genetic technique can be an ideal approach for successful development of attenuated COVID-19 vaccine for priming immune responses in naive hosts followed by parenteral heterologous S or N protein booster vaccine to possibly elicit cross protection against strains within beta-CoV genus (Ng and Tan, 2017; Saif, 2020). Earlier, β-propriolactone inactivated SARS CoV whole-virus vaccine adjuvanted with MF59 elicited promising VN antibody titer in mice and got approval for human use in Europe (Stadler et al., 2005; Gillim-Ross and Subbarao, 2006).
Globally, several institutions have successfully isolated the virus strains of SARS-CoV-2 and started research on the prospects of vaccine development (Zhang et al., 2020). For example, Codagenix, Inc. collaborated with the Serum Institute of India, Ltd. to develop a live-attenuated vaccine against SARS-CoV-2 by “codon deoptimization technology” (Shieber, 2020). Similarly, Johnson & Johnson will attempt to deactivate SARS-CoV-2 which switches off its virulence factors but retains its ability to stimulate immune system. According to the company statement human trials are expected by September 2020 (Ryan, 2020). Also, the researchers at University of Hong Kong developed a live influenza vaccine that expresses SARS-CoV-2 proteins (Cheung 2020). However, the development of live virus vaccines require propagation of high titers of infectious virus and extensive testing to ensure safety which warrants the requirement of biosafety level-3 for production (Gilim-Ross and Subbarao, 2006; Chen et al., 2020). The ADE problem of CoV vaccines is particularly prominent with live or killed whole virus SARS coronavirus vaccines (Jiang et al., 2012; Chen et al., 2020) and incomplete inactivation of virus vaccine is a potential public health threat as well (Gillim-Ross and Subbarao, 2006).