AUTHOR=Chi Hang , Wang Yanqun , Li Entao , Wang Xiwen , Wang Hualei , Jin Hongli , Han Qiuxue , Wang Zhenshan , Wang Xinyue , Zhu Airu , Sun Jing , Zhuang Zhen , Zhang Lu , Ye Jingmeiqi , Wang Haijun , Feng Na , Hu Mingda , Gao Yuwei , Zhao Jincun , Zhao Yongkun , Yang Songtao , Xia Xianzhu TITLE=Inactivated Rabies Virus Vectored MERS-Coronavirus Vaccine Induces Protective Immunity in Mice, Camels, and Alpacas JOURNAL=Frontiers in Immunology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.823949 DOI=10.3389/fimmu.2022.823949 ISSN=1664-3224 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 characterizing 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 efficacy in Ad5-hDPP4-transduced mouse model. These results highlight the inactivated rabies virus-vectored MERS-CoV vaccine as a promising camelids candidate vaccine.