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).