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
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