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).