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ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice.
Vaccine. 2017 06 27; 35(30):3780-3788.V

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) has infected more than 1900 humans, since 2012. The syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. The virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. Therefore, dromedary camels are considered the only animal source of infection. Neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. Here, we developed four vaccine candidates against MERS-CoV based on ChAdOx1 and MVA viral vectors, two candidates per vector. All vaccines contained the full-length spike gene of MERS-CoV; ChAdOx1 MERS vaccines were produced with or without the leader sequence of the human tissue plasminogen activator gene (tPA) where MVA MERS vaccines were produced with tPA, but either the mH5 or F11 promoter driving expression of the spike gene. All vaccine candidates were evaluated in a mouse model in prime only or prime-boost regimens. ChAdOx1 MERS with tPA induced higher neutralising antibodies than ChAdOx1 MERS without tPA. A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. The humoral immunogenicity of a single dose of ChAdOx1 MERS with tPA was equivalent to two doses of MVA MERS (also with tPA). MVA MERS with mH5 or F11 promoter induced similar antibody levels; however, F11 promoter enhanced the cellular immunogenicity of MVA MERS to significantly higher magnitudes. In conclusion, our study showed that MERS-CoV vaccine candidates could be optimized by utilising different viral vectors, various genetic designs of the vectors, or different regimens to increase immunogenicity. ChAdOx1 and MVA vectored vaccines have been safely evaluated in camels and humans and these MERS vaccine candidates should now be tested in camels and in clinical trials.

Authors+Show Affiliations

The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK; King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Electronic address: harbina2@ngha.med.sa.The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK; Department of Zoology, University of Oxford, Oxford, UK.Institute of Virology, Philipps University of Marburg, Marburg, Germany; German Center for Infection Research, TTU Emerging Infections, Germany.The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.Viral Pseudotype Unit, School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB, UK.Viral Pseudotype Unit, School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB, UK.The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.Institute of Virology, Philipps University of Marburg, Marburg, Germany; German Center for Infection Research, TTU Emerging Infections, Germany.The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28579232

Citation

Alharbi, Naif Khalaf, et al. "ChAdOx1 and MVA Based Vaccine Candidates Against MERS-CoV Elicit Neutralising Antibodies and Cellular Immune Responses in Mice." Vaccine, vol. 35, no. 30, 2017, pp. 3780-3788.
Alharbi NK, Padron-Regalado E, Thompson CP, et al. ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice. Vaccine. 2017;35(30):3780-3788.
Alharbi, N. K., Padron-Regalado, E., Thompson, C. P., Kupke, A., Wells, D., Sloan, M. A., Grehan, K., Temperton, N., Lambe, T., Warimwe, G., Becker, S., Hill, A. V. S., & Gilbert, S. C. (2017). ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice. Vaccine, 35(30), 3780-3788. https://doi.org/10.1016/j.vaccine.2017.05.032
Alharbi NK, et al. ChAdOx1 and MVA Based Vaccine Candidates Against MERS-CoV Elicit Neutralising Antibodies and Cellular Immune Responses in Mice. Vaccine. 2017 06 27;35(30):3780-3788. PubMed PMID: 28579232.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice. AU - Alharbi,Naif Khalaf, AU - Padron-Regalado,Eriko, AU - Thompson,Craig P, AU - Kupke,Alexandra, AU - Wells,Daniel, AU - Sloan,Megan A, AU - Grehan,Keith, AU - Temperton,Nigel, AU - Lambe,Teresa, AU - Warimwe,George, AU - Becker,Stephan, AU - Hill,Adrian V S, AU - Gilbert,Sarah C, Y1 - 2017/06/01/ PY - 2017/03/02/received PY - 2017/04/30/revised PY - 2017/05/10/accepted PY - 2017/6/6/pubmed PY - 2018/3/3/medline PY - 2017/6/6/entrez KW - Adenoviral vector KW - ChAdOx1 KW - Coronavirus KW - Immunogenicity KW - MERS-CoV KW - MVA KW - Poxviral vector KW - Prime boost KW - Vaccination KW - Vaccine SP - 3780 EP - 3788 JF - Vaccine JO - Vaccine VL - 35 IS - 30 N2 - The Middle East respiratory syndrome coronavirus (MERS-CoV) has infected more than 1900 humans, since 2012. The syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. The virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. Therefore, dromedary camels are considered the only animal source of infection. Neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. Here, we developed four vaccine candidates against MERS-CoV based on ChAdOx1 and MVA viral vectors, two candidates per vector. All vaccines contained the full-length spike gene of MERS-CoV; ChAdOx1 MERS vaccines were produced with or without the leader sequence of the human tissue plasminogen activator gene (tPA) where MVA MERS vaccines were produced with tPA, but either the mH5 or F11 promoter driving expression of the spike gene. All vaccine candidates were evaluated in a mouse model in prime only or prime-boost regimens. ChAdOx1 MERS with tPA induced higher neutralising antibodies than ChAdOx1 MERS without tPA. A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. The humoral immunogenicity of a single dose of ChAdOx1 MERS with tPA was equivalent to two doses of MVA MERS (also with tPA). MVA MERS with mH5 or F11 promoter induced similar antibody levels; however, F11 promoter enhanced the cellular immunogenicity of MVA MERS to significantly higher magnitudes. In conclusion, our study showed that MERS-CoV vaccine candidates could be optimized by utilising different viral vectors, various genetic designs of the vectors, or different regimens to increase immunogenicity. ChAdOx1 and MVA vectored vaccines have been safely evaluated in camels and humans and these MERS vaccine candidates should now be tested in camels and in clinical trials. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/28579232/ChAdOx1_and_MVA_based_vaccine_candidates_against_MERS_CoV_elicit_neutralising_antibodies_and_cellular_immune_responses_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(17)30656-4 DB - PRIME DP - Unbound Medicine ER -