tetano
Editor, Senior Moderator
Front Immunol
. 2022 Jan 31;13:823949.
doi: 10.3389/fimmu.2022.823949. eCollection 2022.
Inactivated Rabies Virus Vectored MERS-Coronavirus Vaccine Induces Protective Immunity in Mice, Camels, and Alpacas
Hang Chi[SUP] 1 [/SUP], Yanqun Wang[SUP] 2 [/SUP], Entao Li[SUP] 1 [/SUP], Xiwen Wang[SUP] 3 [/SUP], Hualei Wang[SUP] 4 [/SUP], Hongli Jin[SUP] 4 [/SUP], Qiuxue Han[SUP] 1 [/SUP], Zhenshan Wang[SUP] 1 [/SUP], Xinyue Wang[SUP] 1 [/SUP], Airu Zhu[SUP] 2 [/SUP], Jing Sun[SUP] 2 [/SUP], Zhen Zhuang[SUP] 2 [/SUP], Lu Zhang[SUP] 5 [/SUP], Jingmeiqi Ye[SUP] 6 [/SUP], Haijun Wang[SUP] 7 [/SUP], Na Feng[SUP] 1 [/SUP], Mingda Hu[SUP] 8 [/SUP], Yuwei Gao[SUP] 1 [/SUP], Jincun Zhao[SUP] 2 9 10 [/SUP], Yongkun Zhao[SUP] 1 [/SUP], Songtao Yang[SUP] 1 [/SUP], Xianzhu Xia[SUP] 1 [/SUP]
Affiliations
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[SUP]+[/SUP] 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.
Keywords: MERS-CoV; alpaca; camel; mice; rabies virus vector; vaccine.
. 2022 Jan 31;13:823949.
doi: 10.3389/fimmu.2022.823949. eCollection 2022.
Inactivated Rabies Virus Vectored MERS-Coronavirus Vaccine Induces Protective Immunity in Mice, Camels, and Alpacas
Hang Chi[SUP] 1 [/SUP], Yanqun Wang[SUP] 2 [/SUP], Entao Li[SUP] 1 [/SUP], Xiwen Wang[SUP] 3 [/SUP], Hualei Wang[SUP] 4 [/SUP], Hongli Jin[SUP] 4 [/SUP], Qiuxue Han[SUP] 1 [/SUP], Zhenshan Wang[SUP] 1 [/SUP], Xinyue Wang[SUP] 1 [/SUP], Airu Zhu[SUP] 2 [/SUP], Jing Sun[SUP] 2 [/SUP], Zhen Zhuang[SUP] 2 [/SUP], Lu Zhang[SUP] 5 [/SUP], Jingmeiqi Ye[SUP] 6 [/SUP], Haijun Wang[SUP] 7 [/SUP], Na Feng[SUP] 1 [/SUP], Mingda Hu[SUP] 8 [/SUP], Yuwei Gao[SUP] 1 [/SUP], Jincun Zhao[SUP] 2 9 10 [/SUP], Yongkun Zhao[SUP] 1 [/SUP], Songtao Yang[SUP] 1 [/SUP], Xianzhu Xia[SUP] 1 [/SUP]
Affiliations
- PMID: 35173733
- PMCID: PMC8842186
- DOI: 10.3389/fimmu.2022.823949
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[SUP]+[/SUP] 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.
Keywords: MERS-CoV; alpaca; camel; mice; rabies virus vector; vaccine.