Inactivated Rabies Virus Vectored MERS-Coronavirus Vaccine Induces Protective Immunity in Mice, Camels, and Alpacas.

Inactivated Rabies Virus Vectored MERS-Coronavirus Vaccine Induces Protective Immunity in Mice, Camels, and Alpacas.
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灭活狂犬病病毒载体中东呼吸综合征冠状病毒疫苗可诱导小鼠、骆驼和羊驼产生保护性免疫力

DOI:
10.3389/fimmu.2022.823949
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发表时间:
2022
影响因子:
7.3
通讯作者:
Xia X
Xia X
中科院分区:
医学2区
文献类型:
--
作者:
Chi H;Wang Y;Li E;Wang X;Wang H;Jin H;Han Q;Wang Z;Wang X;Zhu A;Sun J;Zhuang Z;Zhang L;Ye J;Wang H;Feng N;Hu M;Gao Y;Zhao J;Zhao Y;Yang S;Xia X

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中东呼吸综合征冠状病毒(MERS-CoV)是一种新出现的冠状病毒,通过骆驼到人的传播引起了频繁的人畜共患事件。有效的骆驼疫苗接种策略可能是降低人类暴露风险的最佳方法。在这里,我们构建了一种灭活的狂犬病病毒载体MERS-CoV疫苗,并在小鼠、骆驼和羊驼中进行了评估。在小鼠中产生了有效的抗原特异性抗体和CD 8 + T细胞应答;此外,疫苗接种减少了MERS-CoV感染小鼠中的病毒复制并加速了病毒清除。此外,在骆驼和羊驼中诱导了针对MERS CoV和狂犬病病毒的保护性抗体应答。令人满意的是,免疫血清显示出针对三种主要MERS-CoV进化枝的广泛的交叉中和活性。为了进一步表征骆驼科动物中诱导的抗体应答,从免疫的羊驼中分离MERS-CoV特异性仅重链抗体(VHH)的可变结构域,并在Ad 5-hDPP 4转导的小鼠模型中显示出有效的预防和治疗功效。这些结果突出了灭活的狂犬病病毒载体MERS-CoV疫苗作为一种有前途的骆驼科候选疫苗。
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.
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