俄罗斯N F Gamaleya国家流行病学和微生物学研究中心Denis Y Logunov团队研究了基于两种外源重组腺病毒载体的两种剂型的COVID-19疫苗的安全性和免疫原性。2020年9月4日，该研究发表在《柳叶刀》杂志上。

研究组研制了一种外源性COVID-19疫苗，由重组腺病毒26（rAd26）载体和重组腺病毒5（rAd5）载体两部分组成，均携带SARS-CoV-2刺突蛋白基因，即rAd26-S和rAd5-S。

为了评估该疫苗的两种剂型（冷冻和冻干）的安全性和免疫原性，研究组在俄罗斯的两家医院进行了两项开放的、非随机的临床1/2期研究，2020年6月18日至8月3日，招募了76名18-60岁的健康成年志愿者，每项研究38名。1期试验中，志愿者在第0天接受肌肉注射1剂rAd26-S或rAd5-S，并在第28天评估这两种疫苗的安全性。在2期试验中（不早于1期试验疫苗接种后5天），志愿者接受初次加强免疫接种，第0天接种rAd26-S，第21天接种rAd5-S。主要结局指标是抗原特异性体液免疫和安全性。

每项研究中，I期试验有9名志愿者接种了rAd26-S，9名志愿者接种了rAd5-S，2期试验中有20名志愿者接种了rAd26-S和rAd5-S。两种疫苗制剂均安全且耐受性良好。最常见的不良事件是注射部位疼痛（44 [58％]）、体温过高（38 [50％]）、头痛（32 [42％]）、虚弱（21 [28％]）以及肌肉和关节疼痛（18 [24％]）。大多数不良事件为轻度，未发现严重不良事件。

所有参与者均产生针对SARS-CoV-2刺突蛋白的抗体。在第42天，冷冻制剂的受体结合域特异性IgG滴度为14703，冻干制剂为11143，冷冻制剂的中和抗体为49.25，冻干制剂为45.95，血清转化率为100％。第28天，所有参与者中均检测到细胞介导的反应，冷冻制剂的中位细胞增殖了2.5％CD4⁺和1.3％CD8⁺，冻干制剂则分别为1.3％CD4⁺和1.1％CD8⁺。

总之，基于外源rAd26和rAd5载体的COVID-19疫苗具有良好的安全性，并在参与者中诱导了强烈体液和细胞免疫应答。

附：英文原文

Title: Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia

Author: Denis Y Logunov, Inna V Dolzhikova, Olga V Zubkova, Amir I Tukhvatullin, Dmitry V Shcheblyakov, Alina S Dzharullaeva, Daria M Grousova, Alina S Erokhova, Anna V Kovyrshina, 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, Nadezhda L Lubenets, Daria A Egorova, Maksim M Shmarov, Natalia A Nikitenko, Lola F Morozova, Elena A Smolyarchuk, Evgeny V Kryukov, Vladimir F Babira, Sergei V Borisevich, Boris S Naroditsky, Alexander L Gintsburg

Issue&Volume: 2020-09-04

Abstract:

Background

We developed a heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector, both carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (rAd26-S and rAd5-S). We aimed to assess the safety and immunogenicity of two formulations (frozen and lyophilised) of this vaccine.

Methods

We did two open, non-randomised phase 1/2 studies at two hospitals in Russia. We enrolled healthy adult volunteers (men and women) aged 18–60 years to both studies. In phase 1 of each study, we administered intramuscularly on day 0 either one dose of rAd26-S or one dose of rAd5-S and assessed the safety of the two components for 28 days. In phase 2 of the study, which began no earlier than 5 days after phase 1 vaccination, we administered intramuscularly a prime-boost vaccination, with rAd26-S given on day 0 and rAd5-S on day 21. Primary outcome measures were antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA on days 0, 14, 21, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (T-cell responses and interferon-γ concentration) and change in neutralising antibodies (detected with a SARS-CoV-2 neutralisation assay). These trials are registered with ClinicalTrials.gov, NCT04436471 and NCT04437875.

Findings

Between June 18 and Aug 3, 2020, we enrolled 76 participants to the two studies (38 in each study). In each study, nine volunteers received rAd26-S in phase 1, nine received rAd5-S in phase 1, and 20 received rAd26-S and rAd5-S in phase 2. Both vaccine formulations were safe and well tolerated. The most common adverse events were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]), and muscle and joint pain (18 [24%]). Most adverse events were mild and no serious adverse events were detected. All participants produced antibodies to SARS-CoV-2 glycoprotein. At day 42, receptor binding domain-specific IgG titres were 14703 with the frozen formulation and 11143 with the lyophilised formulation, and neutralising antibodies were 49·25 with the frozen formulation and 45·95 with the lyophilised formulation, with a seroconversion rate of 100%. Cell-mediated responses were detected in all participants at day 28, with median cell proliferation of 2·5% CD4+ and 1·3% CD8+ with the frozen formulation, and a median cell proliferation of 1·3% CD4+ and 1·1% CD8+ with the lyophilised formulation.

Interpretation

The heterologous rAd26 and rAd5 vector-based COVID-19 vaccine has a good safety profile and induced strong humoral and cellular immune responses in participants. Further investigation is needed of the effectiveness of this vaccine for prevention of COVID-19.

DOI: 10.1016/S0140-6736(20)31866-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31866-3/fulltext