Commentary: Inactivated rabies virus vectored MERS-Coronavirus vaccine induces protective immunity in mice, camels, and alpacas

Induces Protective Immunity in Mice, Camels, and Alpacas (doi: 10.3389/fimmu.2022.823949), was recently published in Frontiers in Immunology (Section: Vaccines and Molecular Therapeutics) (1). In this study, Chi et al. constructed a chimeric rabies virus (RABV) that expressed a genetically modified S1 gene from the Middle East respiratory syndrome coronavirus (MERS-CoV), and then evaluated its potential of virus-vectored vaccine after inactivation in different animals. This study demonstrated that the inactivated S1-expressing RABV was a promising vaccine candidate against MERS-CoV for camelids. Here, we would like to express our scientific opinions on this study.MERS is a severe infectious disease caused by MERS-CoV, initially identified in Saudi Arabia in 2012 (2). Typical signs clinically include fever, cough and shortness of breath in humans.MERS-CoV is a zoonotic virus, which has been identified in dromedary camels in several Member States in the Middle East, Africa and South Asia (3). There are a number of candidate vaccines that have been reported against MERS-CoV, including nucleic acid vaccine (4), subunit vaccine (5), nanoparticle vaccine (6), virus-vectored vaccine (7), and even live-attenuated vaccine (8). Most of the candidate vaccines have been designed using the MERS-CoV S protein, especially the S1 subunit.RABV virion is a bullet-shaped particle, containing a single-stranded, negative-sense RNA genome, coding for five proteins in order: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and RNA-dependent RNA polymerase (L). The RABV can be genetically modified using reverse genetics, whereby a foreign sequence can be inserted into the RABV genome for rescuing a replication-competent chimeric virus (9). This genetically modified RABV, if demonstrated to be able of expressing a foreign antigen that induces immune responses in vivo, would play a potential role in the development of RABV-vectored vaccines, such as live-attenuated vaccines (10)(11), inactivated vaccines (12-13) and replication-deficient vaccines (14)(15).The inactivated RABV-vectored vaccine (IRVV) is a killed version of antigen-expressing RABV, rescued from its cDNA clone using reverse genetics. The development of an IRVV involves the construction of a chimeric RABV cDNA clone, which contains a foreign gene for virus recovery. More importantly, it must be ensured that the target antigen can be incorporated into the envelope of RABV virion (16). The foreign sequence-containing genome and the foreign antigen-containing virion are schematically shown in Figure 1A andB, respectively. Some RABV-expressed antigens will be processed, transported to the cell surface, and finally, as membrane-spanning proteins, embedded into the cellular envelope. Along with budding of RABV virion, the foreign antigen can be incorporated into the viral envelope (13,17). Compared with the live-attenuated vaccine, the IRVV shows a good safety profile in vivo, as evidenced by neither virus mutation nor virulence reversion occurring in IRVV-vaccinated animals.A chimeric RABV, albeit chemically inactivated, can even completely retain its immunogenicity, eliciting not only the anti-RABV immune response, but also more significantly, high-level antibodies against a target pathogen. In the study conducted by Chi et al., the rSRV9-MERS S1 -inoculated mice, camels and alpacas were independently demonstrated to be able of secreting MERS-CoV-specific antibodies, implying its ability to inhibit the MERS-CoV infection in animals.It has been widely demonstrated that inactivated chimeric RABVs have promising potentials in developing IRVVs (1,(12)(13)(17)(18)(19)(20)(21)(22)(23), whereas there are still a few disadvantages to them. For example, IRVVs may be less efficient than live-attenuated RABV-vectored vaccines in immunogenicity. The latter can elicit so potent immune response that a single dose is sufficient for the vaccination of animals, whereas the former are generally involved in the prime-boost vaccination (24)(25). In order to obtain MERS-CoV-specific antibodies at a high level, mice, MERS-CoV has been still regarded as an emerging virus. Although various anti-MERS-CoV candidate vaccines have been recently reported, none of them has been commercially available as yet. In the field of virus-vectored vaccines, Chi et al. carried out their study that was valuable for guiding the development of IRVV. In conclusion, the inactivated rSRV9-MERS S1 was safe for the vaccine-inoculated animals, and induced potent immune responses in vivo. Therefore, this study will pave the way for the construction of virus-vectored vaccines against MERS-CoV in future.