ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques
Autor: | Patrick W. Hanley, Alexandra J. Spencer, Atsushi Okumura, Lizzette Pérez-Pérez, Cameron Bissett, Jonathan E Schulz, Vincent J. Munster, Elizabeth R. Allen, Neeltje van Doremalen, Jyothi N. Purushotham, Sandra Belij-Rammerstorfer, Brandi N. Williamson, Hannah Sharpe, Marta Ulaszewska, Jamie Lovaglio, Ciaran Gilbride, Victoria A. Avanzato, Claire Powers, Amy Flaxman, Dana P. Scott, Julia R Port, Greg Saturday, Trenton Bushmaker, Alka Ishwarbhai, Sarah C. Gilbert, Kimberly Meade-White, Rebecca Rosenke, Daniel B. Wright, Myndi G. Holbrook, Nick J. Edwards, Emmie de Wit, Dan Long, Susan J. Morris, Louisa Rose, Friederike Feldmann, Reshma Kailath, Teresa Lambe |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male viruses Subclass Mice 0302 clinical medicine Respiratory system Lung 0303 health sciences Immunity Cellular Multidisciplinary medicine.diagnostic_test Immunogenicity Vaccination Viral Load 3. Good health medicine.anatomical_structure 030220 oncology & carcinogenesis Spike Glycoprotein Coronavirus Cytokines Female Coronavirus Infections Viral load Bronchoalveolar Lavage Fluid COVID-19 Vaccines Pneumonia Viral Article Adenoviridae 03 medical and health sciences Betacoronavirus Immune system Immunity medicine Animals Viral shedding Pandemics 030304 developmental biology business.industry SARS-CoV-2 COVID-19 Viral Vaccines Th1 Cells Macaca mulatta Immunity Humoral Disease Models Animal 030104 developmental biology Bronchoalveolar lavage Immunoglobulin G Immunology business Respiratory tract |
Zdroj: | bioRxiv Nature |
Popis: | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the coronavirus disease 2019 (COVID-19) pandemic3. Vaccines are an essential countermeasure and are urgently needed to control the pandemic4. Here we show that the adenovirus-vector-based vaccine ChAdOx1 nCoV-19, which encodes the spike protein of SARS-CoV-2, is immunogenic in mice and elicites a robust humoral and cell-mediated response. This response was predominantly mediated by type-1 T helper cells, as demonstrated by the profiling of the IgG subclass and the expression of cytokines. Vaccination with ChAdOx1 nCoV-19 (using either a prime-only or a prime–boost regimen) induced a balanced humoral and cellular immune response of type-1 and type-2 T helper cells in rhesus macaques. We observed a significantly reduced viral load in the bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques that were challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated SARS-CoV-2-infected animals. However, there was no difference in nasal shedding between vaccinated and control SARS-CoV-2-infected macaques. Notably, we found no evidence of immune-enhanced disease after viral challenge in vaccinated SARS-CoV-2-infected animals. The safety, immunogenicity and efficacy profiles of ChAdOx1 nCoV-19 against symptomatic PCR-positive COVID-19 disease will now be assessed in randomized controlled clinical trials in humans. The ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 induces an immune response in rhesus macaques and leads to reduced SARS-CoV-2 viral loads in respiratory tissues and an absence of pneumonia, but not to a reduction in nasal virus shedding, compared with unvaccinated animals. |
Databáze: | OpenAIRE |
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