Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
Emerging microbes & infections - 8(2019), 1 vom: 15., Seite 760-772 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jia, Wenxu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.08.2019 Date Revised 14.12.2020 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/22221751.2019.1620083 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM29748205X |
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| 100 | 1 | |a Jia, Wenxu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 28.08.2019 | ||
| 500 | |a Date Revised 14.12.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a MERS-CoV vaccine | |
| 650 | 4 | |a chimpanzee adenoviral vector | |
| 650 | 4 | |a intranasal immunization | |
| 650 | 4 | |a monoclonal antibody | |
| 650 | 4 | |a receptor binding domain (RBD) | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Drug Carriers |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a Vaccines, Synthetic |2 NLM | |
| 650 | 7 | |a Viral Vaccines |2 NLM | |
| 700 | 1 | |a Channappanavar, Rudragouda |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Mingxi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Haixia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shuyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Panpan |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jiuyang |e verfasserin |4 aut | |
| 700 | 1 | |a Shan, Sisi |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Xuanling |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xinquan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jincun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Dongming |e verfasserin |4 aut | |
| 700 | 1 | |a Perlman, Stanley |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Linqi |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:8 |g year:2019 |g number:1 |g day:15 |g pages:760-772 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/22221751.2019.1620083 |3 Volltext |
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