6.5 Live vector vaccines
Live vector vaccines constitute the live viruses acting as vectors which
express the desired heterologous antigens of targeted viruses. This
vaccine strategy combines the strong immunogenicity property of live
attenuated vaccines and the safety aspect of subunit vaccines, and this
strategy is widely used to induce cellular immunity in host (Zhang et
al., 2020). Reverse genetics approach has been successfully used to
develop live-attenuated viruses by inactivating exonuclease effects of
non-structural protein 14 (nsp 14) or by deletion of the structural
envelop protein in SARS-CoV (Graham et al., 2013). By adopting the
similar approach, H strain of avian infectious bronchitis virus (IBV)
can be used to express the antigenic determinants of SARS-CoV and elicit
humoral as well as cell-mediated immunity (Bijlenga, 2005; Dhama et al.,
2020). Thus, following safety evaluation in non-human primates, the
recombinant avian IBV can act as a prospective vector vaccine for
SARS-CoV-2 (Zhang and Liu, 2020). A number of research institutions and
pharmaceutical companies have taken up the process of live vector
vaccine development for SARS-CoV-2. Greffex Inc. and Tonix
Pharmaceuticals are working on the development of adenovirus vector and
horsepox virus vector (TNX-1800) vaccines against SARS-CoV-2,
respectively. However, using Greffex Vector Platform Greffex has already
advanced to the stage of animal testing (Zhang et al., 2020). Similarly,
Johnson & Johnson took to COVID-19 vaccine development by employing
Janssen’s AdVac® adenoviral vector and their PER.C6® cell line
technology (J&J, 2020; Cheung, 2020).
The recombinant adenovirus vectors of chimpanzee origin (CHAd63) have
been used for development of SARS and MERS vaccines to overcome the
widespread pre-existing immunity against human adenoviruses. The CHAd63
expresses SARS-CoV S or N protein or MERS-CoV S protein and was shown to
confer different levels of protection in mice, ferret, and nonhuman
primates following challenge (Roper and Rehm, 2009; Enjuanes et al.,
2008; Schindewolf and Menachery, 2019). The immunization of BALB/c mice
with recombinant adenovirus vector vaccine expressing MERS-CoV S protein
induced systemic and mucosal antibodies along with memory T-cell
response in lungs which indicates the potential of this vaccine to
confer protection against MERS-CoV (Kim et al., 2019). Other vectors for
SARS and MERS vaccines which could be the prospective vectors for
COVID-19 vaccines include modified vaccinia ankara (MVA), parainfluenza
virus, measles virus, Newcastle disease virus, and vesicular stomatitis
virus which have been shown to express S and/or N proteins of SARS- and
MERS-CoV (Roper and Rehm, 2009; Enjuanes et al., 2008; Schindewolf and
Menachery, 2019). Even the use of Rabies virus as viral vector has shown
promising results in BALB/c mice against MERS-CoV by expressing S
protein of the same and eliciting higher levels of cellular immunity and
earlier antibody response (Li et al., 2020). After the outbreak of SARS
in 2002, a live attenuated Chimeric bovine/human parainfluenza virus 3
(BHPIV3) was utilized as a vector for the expression of S, N, M, and E
proteins of SARS-CoV. However, only vector vaccine expressing S protein
was successful in providing protection against SARS in hamsters
(Buchholz et al., 2004; Gillim-Ross and Subbarao, 2006). Also, the
vaccines expressing multiple proteins other than S protein could not
provide protection to hamsters which suggests that only S protein is a
promising antigen in vectored vaccines. On the other hand, vaccination
of African green monkey by BHPIV3 vector expressing S protein of
SARS-CoV conferred protection as well as prevented nasal virus shedding
following challenge (Bukreyev et al., 2004).