1/1
2 files

Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection

dataset
posted on 25.05.2019, 11:50 by Wenxu Jia, Rudragouda Channappanavar, Chao Zhang, Mingxi Li, Haixia Zhou, Shuyuan Zhang, Panpan Zhou, Jiuyang Xu, Sisi Shan, Xuanling Shi, Xinquan Wang, Jincun Zhao, Dongming Zhou, Stanley Perlman, Linqi Zhang

The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.

Funding

This work was support by grants from National Natural Science Foundation of China [grant number 81530065], [grant number 81471929]; the Grand Challenges China [grant number 81661128042]; National Plan on Key Basic Research and Development [grant number 2016YFC1200902]; the National Science and Technology Development Agency [grant number 2017ZX10201101], [grant number 2018ZX10731101] to L.Z., in part by grants from the NIH PO1AI060699 and RO1AI129269 to S.P. and Strategic Priority Research Program of the Chinese Academy of Science [grant number XBD29040000]; the National Science and Technology Development Agency [grant number 2018ZX10101004], [grant number 2016YFC1201000] to D.Z.

History