Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is an emergent coronavirus that has caused frequent zoonotic events through camel-to-human spillover. An effective camelid vaccination strategy is probably the best way to reduce human exposure risk. Here, we constructed and evaluated an inactivated rabies virus-vectored MERS-CoV vaccine in mice, camels, and alpacas. Potent antigen-specific antibody and CD8+ T-cell responses were generated in mice; moreover, the vaccination reduced viral replication and accelerated virus clearance in MERS-CoV-infected mice. Besides, protective antibody responses against both MERS-CoV and rabies virus were induced in camels and alpacas. Satisfyingly, the immune sera showed broad cross-neutralizing activity against the three main MERS-CoV clades. For further characterization of the antibody response induced in camelids, MERS-CoV-specific variable domains of heavy-chain-only antibody (VHHs) were isolated from immunized alpacas and showed potent prophylactic and therapeutic efficacies in the Ad5-hDPP4-transduced mouse model. These results highlight the inactivated rabies virus-vectored MERS-CoV vaccine as a promising camelid candidate vaccine.
Highlights
The Middle East respiratory syndrome (MERS) is an acute viral infectious disease caused by a zoonotic coronavirus (MERSCoV) that was first identified in Saudi Arabia in 2012 [1, 2]
Four- to 6-week-old Institute of Cancer Research (ICR) adult mice and 14-day-old ICR suckling mice i.c. injected with serial dilutions of rSRV9-MERSS1 did not show any clinical signs or lethality
The results of intracerebral challenge in 5-day-old ICR suckling mice demonstrate that the neurovirulence of rSRV9-MERSS1 was reduced compared to that of the parental virus rSRV9 (Table 1), indicating an increased safety profile
Summary
The Middle East respiratory syndrome (MERS) is an acute viral infectious disease caused by a zoonotic coronavirus (MERSCoV) that was first identified in Saudi Arabia in 2012 [1, 2]. Camelid vaccine candidates targeting MERS-CoV S surface glycoprotein developed by different research groups have been reported, mainly utilizing a viral vector-based vaccine, DNA-based vaccine, or subunit vaccine platform [10, 11, 15,16,17,18]. Compared with live viral vectorbased vaccines, inactivated recombinant rabies virus-vectored vaccines lessen the concerns of safety and production scalability [23,24,25,26,27,28,29]. In the current study, we developed an inactivated viral vector vaccine against MERSCoV, based on a consensus MERS-CoV truncated S1 subunit glycoprotein, and investigated the immune efficacy of the candidate vaccine in mice, camels, and alpacas against multiple MERS-CoV clade strains. This study highlights inactivated rabies virus vectored MERS-CoV vaccine as a safe, immunogenic, and efficacious vaccine that warrants further assessment
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