A single dose of ChAdOx1 MERS provides protective immunity in rhesus macaques

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Abstract

Prime-only vaccination with ChAdOx1 MERS protects against HCoV-EMC/2012 in NHP and a variety of MERS-CoV strains in mice.

Abstract

Developing a vaccine to protect against the lethal effects of the many strains of coronavirus is critical given the current global pandemic. For Middle East respiratory syndrome coronavirus (MERS-CoV), we show that rhesus macaques seroconverted rapidly after a single intramuscular vaccination with ChAdOx1 MERS. The vaccine protected against respiratory injury and pneumonia and reduced viral load in lung tissue by several orders of magnitude. MERS-CoV replication in type I and II pneumocytes of ChAdOx1 MERS–vaccinated animals was absent. A prime-boost regimen of ChAdOx1 MERS boosted antibody titers, and viral replication was completely absent from the respiratory tract tissue of these rhesus macaques. We also found that antibodies elicited by ChAdOx1 MERS in rhesus macaques neutralized six different MERS-CoV strains. Transgenic human dipeptidyl peptidase 4 mice vaccinated with ChAdOx1 MERS were completely protected against disease and lethality for all different MERS-CoV strains. The data support further clinical development of ChAdOx1 MERS.

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Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche

G. Kärber (1931)

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Evaluation of candidate vaccine approaches for MERS-CoV

Lingshu Wang, Wei Shi, M Joyce … (2015)

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.

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Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques.

Emmie de Wit, Angela L Rasmussen, Darryl Falzarano … (2013)

In 2012, a novel betacoronavirus, designated Middle East respiratory syndrome coronavirus or MERS-CoV and associated with severe respiratory disease in humans, emerged in the Arabian Peninsula. To date, 108 human cases have been reported, including cases of human-to-human transmission. The availability of an animal disease model is essential for understanding pathogenesis and developing effective countermeasures. Upon a combination of intratracheal, ocular, oral, and intranasal inoculation with 7 × 10(6) 50% tissue culture infectious dose of the MERS-CoV isolate HCoV-EMC/2012, rhesus macaques developed a transient lower respiratory tract infection. Clinical signs, virus shedding, virus replication in respiratory tissues, gene expression, and cytokine and chemokine profiles peaked early in infection and decreased over time. MERS-CoV caused a multifocal, mild to marked interstitial pneumonia, with virus replication occurring mainly in alveolar pneumocytes. This tropism of MERS-CoV for the lower respiratory tract may explain the severity of the disease observed in humans and the, up to now, limited human-to-human transmission.

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Journal

Journal ID (nlm-ta): Sci Adv

Journal ID (iso-abbrev): Sci Adv

Journal ID (publisher-id): SciAdv

Journal ID (hwp): advances

Title: Science Advances

Publisher: American Association for the Advancement of Science

ISSN (Electronic): 2375-2548

Publication date Collection: June 2020

Publication date (Electronic): 10 June 2020

Volume: 6

Issue: 24

Electronic Location Identifier: eaba8399

Affiliations

[1 ]Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA.

[2 ]Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.

[3 ]Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.

[4 ]The Jenner Institute, University of Oxford, Oxford, UK.

[5 ]Transmission Biology Group, The Pirbright Institute, Pirbright, Woking, UK.

Author notes

[* ]Corresponding author. Email: neeltje.vandoremalen@ 123456nih.gov (N.v.D.); sarah.gilbert@ 123456ndm.ox.ac.uk (S.C.G.); vincent.munster@ 123456nih.gov (V.J.M.)

Author information

Neeltje van Doremalen http://orcid.org/0000-0003-4368-6359

Friederike Feldmann http://orcid.org/0000-0002-1363-1077

Robert J. Fischer http://orcid.org/0000-0002-1816-472X

Atsushi Okumura http://orcid.org/0000-0002-7779-3059

Patrick W. Hanley http://orcid.org/0000-0003-2300-1818

Nick J. Edwards http://orcid.org/0000-0002-7030-7839

Teresa Lambe http://orcid.org/0000-0001-7711-897X

Sarah C. Gilbert http://orcid.org/0000-0002-6823-9750

Vincent J. Munster http://orcid.org/0000-0002-2288-3196

Article

Publisher ID: aba8399

DOI: 10.1126/sciadv.aba8399

PMC ID: 7286676

PubMed ID: 32577525

SO-VID: 21280a94-96a1-4245-a0a2-9a555b2bd348

Copyright © Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

History

Date received : 09 January 2020

Date accepted : 16 April 2020

Date: 01 May 2020

Funding

Funded by: doi http://dx.doi.org/10.13039/100006492, Division of Intramural Research, National Institute of Allergy and Infectious Diseases;

Award ID: 1ZIAAI001179-01

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A single dose of ChAdOx1 MERS provides protective immunity in rhesus macaques

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Most cited references 25

Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche

Evaluation of candidate vaccine approaches for MERS-CoV

Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques.

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