Journal
EMERGING MICROBES & INFECTIONS
Volume 8, Issue 1, Pages 760-772Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/22221751.2019.1620083
Keywords
MERS-CoV vaccine; chimpanzee adenoviral vector; receptor binding domain (RBD); intranasal immunization; monoclonal antibody
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Funding
- National Natural Science Foundation of China [81530065, 81471929]
- Grand Challenges China [81661128042]
- National Plan on Key Basic Research and Development [2016YFC1200902]
- National Science and Technology Development Agency [2018ZX10101004, 2016YFC1201000, 2017ZX10201101, 2018ZX10731101]
- NIH [PO1AI060699, RO1AI129269]
- Strategic Priority Research Program of the Chinese Academy of Science [XBD29040000]
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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 naive 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.
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