ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques

被引:13
|
作者
van Doremalen, Neeltje [1 ]
Lambe, Teresa [2 ]
Spencer, Alexandra [2 ]
Belij-Rammerstorfer, Sandra [2 ]
Purushotham, Jyothi N. [1 ,2 ]
Port, Julia R. [1 ]
Avanzato, Victoria A. [1 ]
Bushmaker, Trenton [1 ]
Flaxman, Amy [2 ]
Ulaszewska, Marta [2 ]
Feldmann, Friederike [3 ]
Allen, Elizabeth R. [2 ]
Sharpe, Hannah [2 ]
Schulz, Jonathan [1 ]
Holbrook, Myndi [1 ]
Okumura, Atsushi [1 ]
Meade-White, Kimberly [1 ]
Perez-Perez, Lizzette [1 ]
Edwards, Nick J. [2 ]
Wright, Daniel [2 ]
Bissett, Cameron [2 ]
Gilbride, Ciaran [2 ]
Williamson, Brandi N. [1 ]
Rosenke, Rebecca [3 ]
Long, Dan [3 ]
Ishwarbhai, Alka [2 ]
Kailath, Reshma [2 ]
Rose, Louisa [2 ]
Morris, Susan [2 ]
Powers, Claire [2 ]
Lovaglio, Jamie [3 ]
Hanley, Patrick W. [3 ]
Scott, Dana [3 ]
Saturday, Greg [3 ]
de Wit, Emmie [1 ]
Gilbert, Sarah C. [2 ]
Munster, Vincent J. [1 ]
机构
[1] NIAID, Lab Virol, NIH, Hamilton, MT 59840 USA
[2] Univ Oxford, Jenner Inst, Oxford, England
[3] NIAID, Rocky Mt Vet Branch, NIH, Hamilton, MT USA
基金
美国国家卫生研究院; 英国工程与自然科学研究理事会;
关键词
ACUTE RESPIRATORY SYNDROME; IMMUNIZATION; MICE;
D O I
10.1038/s41586-020-2608-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019(1,2)and is responsible for the coronavirus disease 2019 (COVID-19) pandemic(3). Vaccines are an essential countermeasure and are urgently needed to control the pandemic(4). 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.
引用
收藏
页码:578 / +
页数:15
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