基于rAd26和rAd5载体的异源COVID

作者：杨超月

本期文章：《柳叶刀》：Online/在线发表

俄罗斯联邦卫生部Denis Y Logunov团队研究了基于rAd26和rAd5载体的异源初免-加强免疫COVID-19疫苗的安全性和有效性。2021年2月2日，该成果发表在《柳叶刀》杂志上。

以异源重组腺病毒（rAd）为基础的疫苗Gam-COVID-Vac（Sputnik V）在1/2期临床试验的参与者中显示出良好的安全性，并诱导了强烈的体液和细胞免疫应答。研究组对3期临床试验进行中期分析，得出了关于Gam-COVID-Vac疗效和安全性的初步结果。

研究组在俄罗斯莫斯科的25家医院和综合诊所进行了一项随机、双盲、安慰剂对照的临床3期试验，招募年龄至少为18岁、SARS-CoV-2 PCR和IgG及IgM检测均为阴性、入组前14天内未患传染病、入组前30天内未接种其他疫苗的参与者。按年龄组分层，将参与者按3：1随机分配，分别接种疫苗或安慰剂。疫苗采用初免-加强免疫策略进行肌肉注射接种（0.5ml/剂），第一剂（rAd26）和第二剂（rAd5）之间间隔21天，这两种载体都携带全长SARS-CoV-2刺突蛋白的基因。主要结局是接种第一剂疫苗后第21天感染PCR确诊的COVID-19的参与者比例。

2020年9月7日至11月24日，共有21 977名成人被随机分配到疫苗组（n=16 501）或安慰剂组（n=5476）。共有19?866人接种了两剂疫苗或安慰剂，并纳入主要结果分析。从第一次注射疫苗后21天（第2次注射当天）起，疫苗组的14 964名参与者中有16名（0.1%）确诊COVID-19，安慰剂组的4902名参与者中有62名（1.3%）确诊，疫苗有效性为91.6%。

大多数报告的不良事件为1级（7966例总事件中有7485例[94.0%]）。疫苗组的16?427名参与者中有45名（0.3%）出现严重不良事件，安慰剂组的5435名参与者中有23名（0.4%）；经独立数据监测委员会确认，严重不良事件均与疫苗接种无关。研究期间报告了4例死亡（疫苗组有3例，安慰剂组有1例），死亡均与疫苗无关。

这项Gam-COVID-Vac 3期临床试验的中期分析显示，该疫苗对COVID-19有91.6%的疗效，且耐受性良好。

附：英文原文

Title: Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia

Author: Denis Y Logunov, Inna V Dolzhikova, Dmitry V Shcheblyakov, Amir I Tukhvatulin, Olga V Zubkova, Alina S Dzharullaeva, Anna V Kovyrshina, Nadezhda L Lubenets, Daria M Grousova, Alina S Erokhova, Andrei G Botikov, Fatima M Izhaeva, Olga Popova, Tatiana A Ozharovskaya, Ilias B Esmagambetov, Irina A Favorskaya, Denis I Zrelkin, Daria V Voronina, Dmitry N Shcherbinin, Alexander S Semikhin, Yana V Simakova, Elizaveta A Tokarskaya, Daria A Egorova, Maksim M Shmarov, Natalia A Nikitenko, Vladimir A Gushchin, Elena A Smolyarchuk, Sergey K Zyryanov, Sergei V Borisevich, Boris S Naroditsky, Alexander L Gintsburg

Issue&Volume: 2021-02-02

Abstract:

Background

A heterologous recombinant adenovirus (rAd)-based vaccine, Gam-COVID-Vac (Sputnik V), showed a good safety profile and induced strong humoral and cellular immune responses in participants in phase 1/2 clinical trials. Here, we report preliminary results on the efficacy and safety of Gam-COVID-Vac from the interim analysis of this phase 3 trial.

Methods

We did a randomised, double-blind, placebo-controlled, phase 3 trial at 25 hospitals and polyclinics in Moscow, Russia. We included participants aged at least 18 years, with negative SARS-CoV-2 PCR and IgG and IgM tests, no infectious diseases in the 14 days before enrolment, and no other vaccinations in the 30 days before enrolment. Participants were randomly assigned (3:1) to receive vaccine or placebo, with stratification by age group. Investigators, participants, and all study staff were masked to group assignment. The vaccine was administered (0·5 mL/dose) intramuscularly in a prime-boost regimen: a 21-day interval between the first dose (rAd26) and the second dose (rAd5), both vectors carrying the gene for the full-length SARS-CoV-2 glycoprotein S. The primary outcome was the proportion of participants with PCR-confirmed COVID-19 from day 21 after receiving the first dose. All analyses excluded participants with protocol violations: the primary outcome was assessed in participants who had received two doses of vaccine or placebo, serious adverse events were assessed in all participants who had received at least one dose at the time of database lock, and rare adverse events were assessed in all participants who had received two doses and for whom all available data were verified in the case report form at the time of database lock. The trial is registered at ClinicalTrials.gov (NCT04530396).

Findings

Between Sept 7 and Nov 24, 2020, 21977 adults were randomly assigned to the vaccine group (n=16501) or the placebo group (n=5476). 19866 received two doses of vaccine or placebo and were included in the primary outcome analysis. From 21 days after the first dose of vaccine (the day of dose 2), 16 (0·1%) of 14964 participants in the vaccine group and 62 (1·3%) of 4902 in the placebo group were confirmed to have COVID-19; vaccine efficacy was 91·6% (95% CI 85·6–95·2). Most reported adverse events were grade 1 (7485 [94·0%] of 7966 total events). 45 (0·3%) of 16427 participants in the vaccine group and 23 (0·4%) of 5435 participants in the placebo group had serious adverse events; none were considered associated with vaccination, with confirmation from the independent data monitoring committee. Four deaths were reported during the study (three [<0·1%] of 16 427 participants in the vaccine group and one [<0·1%] of 5435 participants in the placebo group), none of which were considered related to the vaccine.

Interpretation

This interim analysis of the phase 3 trial of Gam-COVID-Vac showed 91·6% efficacy against COVID-19 and was well tolerated in a large cohort.

DOI: 10.1016/S0140-6736(21)00234-8

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00234-8/fulltext

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