牛津大學ChAdOx1 nCoV-19疫苗的安全性和有效性分析
作者：
小柯機器人發布時間：2020/12/10 16:36:25
英國牛津大學Andrew J Pollard團隊研究了ChAdOx1 nCoV-19疫苗抗SARS-CoV-2感染的安全性和有效性。2020年12月8日，該研究發表在《柳葉刀》雜誌上。
若存在一種針對SARS-CoV-2的安全有效疫苗，且廣泛接種，則有助於控制COVID-19大流行。研究組在四項試驗的匯總中期分析中評估了ChAdOx1 nCoV-19疫苗的安全性和有效性。
研究組在英國、巴西和南非進行了四項雙盲的隨機對照試驗， 招募18歲及以上的參與者，將其按1：1隨機分配，分別接種ChAdOx1 nCoV-19疫苗或對照疫苗（腦膜炎球菌A、C、W和Y結合疫苗或生理鹽水）。主要觀察指標為第二次疫苗接種後14天以上血清陰性、核酸檢測陽性的有症狀的Covid-19。
2020年4月23日至11月4日，共有23848名參與者入組，其中11636名參與者（英國7548名，巴西4088名）被納入中期主要療效分析。在接種了兩劑標準劑量疫苗的參與者中，疫苗效力為62.1%；在先接種低劑量、後接種標準劑量的參與者中，疫苗效力為90.0%。兩組的總體疫苗效力為70.4％。
在初次接種後的21天，對照組中有10例參與者因COVID-19住院，其中2例為重症COVID-19，1例最終死亡。安全隨訪74341人-月後，共有168名參與者發生了175次嚴重不良事件，其中ChAdOx1 nCoV-19組發生了84次事件，而對照組發生了91次。有三次事件被歸類為可能與疫苗有關，其中ChAdOx1 nCoV-19組一件，對照組一件，未分組的參與者中一件。
該試驗中期分析表明，ChAdOx1 nCoV-19安全耐受，可有效預防COVID-19。
附：英文原文
Title: Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK
Author: Merryn Voysey, Sue Ann Costa Clemens, Shabir A Madhi, Lily Y Weckx, Pedro M Folegatti, Parvinder K Aley, Brian Angus, Vicky L Baillie, Shaun L Barnabas, Qasim E Bhorat, Sagida Bibi, Carmen Briner, Paola Cicconi, Andrea M Collins, Rachel Colin-Jones, Clare L Cutland, Thomas C Darton, Keertan Dheda, Christopher J A Duncan, Katherine R W Emary, Katie J Ewer, Lee Fairlie, Saul N Faust, Shuo Feng, Daniela M Ferreira, Adam Finn, Anna L Goodman, Catherine M Green, Christopher A Green, Paul T Heath, Catherine Hill, Helen Hill, Ian Hirsch, Susanne H C Hodgson, Alane Izu, Susan Jackson, Daniel Jenkin, Carina C D Joe, Simon Kerridge, Anthonet Koen, Gaurav Kwatra, Rajeka Lazarus, Alison M Lawrie, Alice Lelliott, Vincenzo Libri, Patrick J Lillie, Raburn Mallory, Ana V A Mendes, Eveline P Milan, Angela M Minassian, Alastair McGregor, Hazel Morrison, Yama F Mujadidi, Anusha Nana, Peter J O』Reilly, Sherman D Padayachee, Ana Pittella, Emma Plested, Katrina M Pollock, Maheshi N Ramasamy, Sarah Rhead, Alexandre V Schwarzbold, Nisha Singh, Andrew Smith, Rinn Song, Matthew D Snape, Eduardo Sprinz, Rebecca K Sutherland, Richard Tarrant, Emma C Thomson, M Estée Trk
Issue&Volume: 2020-12-08
Abstract:
Background
A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.
Methods
This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5×1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1-relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674.
Findings
Between April 23 and Nov 4, 2020, 23848 participants were enrolled and 11636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation.
Interpretation
ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.
DOI: 10.1016/S0140-6736(20)32661-1
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext