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Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection.
Emerg Microbes Infect. 2019; 8(1):760-772.EM

Abstract

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.

Authors+Show Affiliations

a Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences , School of Medicine, Tsinghua University , Beijing , People's Republic of China.b Department of Microbiology and Immunology , The University of Iowa , Iowa City , IA , USA. c Department of Acute and Tertiary Care, and the Institute for the Study of Host-Pathogen Systems , University of Tennessee Health Science Center , Memphis , TN , USA.d School of Medicine and Life Sciences, Nanjing University of Chinese Medicine , Nanjing , People's Republic of China. e Key Laboratory of Molecular Virology & Immunology, Vaccine Research Center , Institut Pasteur of Shanghai, Chinese Academy of Sciences , Shanghai , People's Republic of China.a Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences , School of Medicine, Tsinghua University , Beijing , People's Republic of China.f The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy , School of Life Sciences, Tsinghua University , Beijing , People's Republic of China.f The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy , School of Life Sciences, Tsinghua University , Beijing , People's Republic of China.a Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences , School of Medicine, Tsinghua University , Beijing , People's Republic of China.a Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences , School of Medicine, Tsinghua University , Beijing , People's Republic of China.a Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences , School of Medicine, Tsinghua University , Beijing , People's Republic of China.a Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences , School of Medicine, Tsinghua University , Beijing , People's Republic of China.f The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy , School of Life Sciences, Tsinghua University , Beijing , People's Republic of China.g State Key Laboratory of Respiratory Disease , Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University , Guangzhou , People's Republic of China.e Key Laboratory of Molecular Virology & Immunology, Vaccine Research Center , Institut Pasteur of Shanghai, Chinese Academy of Sciences , Shanghai , People's Republic of China.b Department of Microbiology and Immunology , The University of Iowa , Iowa City , IA , USA. g State Key Laboratory of Respiratory Disease , Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University , Guangzhou , People's Republic of China.a Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences , School of Medicine, Tsinghua University , Beijing , People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31130102

Citation

Jia, Wenxu, et al. "Single Intranasal Immunization With Chimpanzee Adenovirus-based Vaccine Induces Sustained and Protective Immunity Against MERS-CoV Infection." Emerging Microbes & Infections, vol. 8, no. 1, 2019, pp. 760-772.
Jia W, Channappanavar R, Zhang C, et al. Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection. Emerg Microbes Infect. 2019;8(1):760-772.
Jia, W., Channappanavar, R., Zhang, C., Li, M., Zhou, H., Zhang, S., Zhou, P., Xu, J., Shan, S., Shi, X., Wang, X., Zhao, J., Zhou, D., Perlman, S., & Zhang, L. (2019). Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection. Emerging Microbes & Infections, 8(1), 760-772. https://doi.org/10.1080/22221751.2019.1620083
Jia W, et al. Single Intranasal Immunization With Chimpanzee Adenovirus-based Vaccine Induces Sustained and Protective Immunity Against MERS-CoV Infection. Emerg Microbes Infect. 2019;8(1):760-772. PubMed PMID: 31130102.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection. AU - Jia,Wenxu, AU - Channappanavar,Rudragouda, AU - Zhang,Chao, AU - Li,Mingxi, AU - Zhou,Haixia, AU - Zhang,Shuyuan, AU - Zhou,Panpan, AU - Xu,Jiuyang, AU - Shan,Sisi, AU - Shi,Xuanling, AU - Wang,Xinquan, AU - Zhao,Jincun, AU - Zhou,Dongming, AU - Perlman,Stanley, AU - Zhang,Linqi, PY - 2019/5/28/entrez PY - 2019/5/28/pubmed PY - 2019/8/29/medline KW - MERS-CoV vaccine KW - chimpanzee adenoviral vector KW - intranasal immunization KW - monoclonal antibody KW - receptor binding domain (RBD) SP - 760 EP - 772 JF - Emerging microbes & infections JO - Emerg Microbes Infect VL - 8 IS - 1 N2 - 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. SN - 2222-1751 UR - https://www.unboundmedicine.com/medline/citation/31130102/Single_intranasal_immunization_with_chimpanzee_adenovirus_based_vaccine_induces_sustained_and_protective_immunity_against_MERS_CoV_infection_ L2 - https://www.tandfonline.com/doi/full/10.1080/22221751.2019.1620083 DB - PRIME DP - Unbound Medicine ER -