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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)760-772
Number of pages13
JournalEmerging Microbes and Infections
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2019

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Adenovirus Vaccines
Coronavirus Infections
Pan troglodytes
Immunity
Immunization
Dipeptidyl Peptidase 4
Protein S
Neutralizing Antibodies
Coronavirus Spike Glycoproteins
Camelus
Middle East Respiratory Syndrome Coronavirus
Adenoviridae
Immune Sera
Vaccines
Monoclonal Antibodies
T-Lymphocytes
Survival
Antibodies

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Epidemiology
  • Microbiology
  • Immunology
  • Drug Discovery
  • Virology
  • Infectious Diseases

Cite this

Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection. / Jia, Wenxu; Channappanavar, Rudragouda; Zhang, Chao; Li, Mingxi; Zhou, Haixia; Zhang, Shuyuan; Zhou, Panpan; Xu, Jiuyang; Shan, Sisi; Shi, Xuanling; Wang, Xinquan; Zhao, Jincun; Zhou, Dongming; Perlman, Stanley; Zhang, Linqi.

In: Emerging Microbes and Infections, Vol. 8, No. 1, 01.01.2019, p. 760-772.

Research output: Contribution to journalArticle

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 and Infections, vol. 8, no. 1, pp. 760-772. https://doi.org/10.1080/22221751.2019.1620083
Jia, Wenxu ; Channappanavar, Rudragouda ; Zhang, Chao ; Li, Mingxi ; Zhou, Haixia ; Zhang, Shuyuan ; Zhou, Panpan ; Xu, Jiuyang ; Shan, Sisi ; Shi, Xuanling ; Wang, Xinquan ; Zhao, Jincun ; Zhou, Dongming ; Perlman, Stanley ; Zhang, Linqi. / Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection. In: Emerging Microbes and Infections. 2019 ; Vol. 8, No. 1. pp. 760-772.
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