Safety and immunogenicity of heterologous boost immunization with an adenovirus type-5-vectored and protein-subunit-based COVID-19 vaccine (Convidecia/ZF2001): A randomized, observer-blinded, placebo-controlled trial.
Safety and immunogenicity of heterologous boost immunization with an adenovirus type-5-vectored and protein-subunit-based COVID-19 vaccine (Convidecia/ZF2001): A randomized, observer-blinded, placebo-controlled trial.
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DOI：
10.1371/journal.pmed.1003953
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发表时间：
2022-05
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影响因子：
15.8
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异源加强疫苗接种已被提议作为引发更强、更广泛或更持久免疫力的一种选择。我们评估了重组腺病毒5型载体2019冠状病毒病（COVID-19）疫苗（Convidecia，以下简称CV）和基于蛋白质亚基的COVID-19疫苗（ZF2001，以下简称ZF）异源免疫的安全性和免疫原性。我们进行了一项随机、观察者盲法、安慰剂对照试验，在中国江苏招募了 18 岁或以上、接受过 1 剂 Convidecia、无严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染史的健康成年人。 60 名参与者被随机分配 (2:1)，在初免后 28 天注射 1 剂 ZF2001 或安慰剂对照（三价灭活流感疫苗 (TIV)），并在 5 个月时接受第三次注射 ZF2001，分别称为 CV/ZF/ZF (D0-D28-M5) 和 CV/ZF (D0-M5) 方案。 60 名参与者被随机分配 (2:1)，在启动后 56 天接受 1 剂 ZF2001 或 TIV，并在 6 个月时接受第三次注射 ZF2001，分别称为 CV/ZF/ZF (D0-D56-M6) 和 CV/ZF (D0-M6) 方案。参与者和研究人员不知道所接种的疫苗，但不知道加强间隔。主要终点是针对野生型 SARS-CoV-2 的中和抗体的几何平均滴度 (GMT) 和 7 天引起的不良反应。主要分析是在意向治疗人群中进行的。 2021年4月7日至2021年5月6日期间，120名符合条件的参与者被随机分配在启动后28天零5个月接受ZF2001/ZF2001（n = 40）或TIV/ZF2001（n = 20），并接受ZF2001/ZF2001（n = 40）或TIV/ZF2001（n = 20) 启动后 56 天零 6 个月。其中，7名参与者没有接受第三次ZF2001注射。共有26名受试者（21.7%）在加强疫苗接种后7天内报告出现不良反应，所有报告的不良反应均为轻度，其中CV/ZF/ZF（D0-D28-M5）方案13名（32.5%），CV/ZF（D0-M5）方案7名（35.0%），CV/ZF/ZF方案4名（10.0%） (D0-D56-M6) 方案，CV/ZF (D0-M6) 方案中分别有 2 个 (10.0%)。首次加强后 14 天，初免后 28 天和 56 天接受 ZF2001 的受者中和抗体的 GMT 分别为 18.7（95% CI 13.7 至 25.5）和 25.9（17.0 至 39.3），几何平均比率为 2.0（1.2 至 3.5）和 3.4（1.8 至 3.5）。 6.4) 与 TIV 相比。第二次中和抗体加强后 14 天的 GMT 在 CV/ZF/ZF (D0-D28-M5) 方案中增加至 107.2（73.7 至 155.8），在 CV/ZF/ZF (D0-D56-M6) 方案中增加至 141.2（83.4 至 238.8）。 CV/ZF (D0-M5) 和 CV/ZF (D0-M6) 的两剂量方案诱导的抗体水平与 3 剂量方案引起的抗体水平相当，GMT 分别为 90.5 (45.6, 179.8) 和 94.1 (44.0, 200.9)。研究的局限性包括在现实环境中缺乏疫苗有效性以及目前缺乏免疫持久性数据。使用 Convidecia 初次接种后使用 ZF2001 进行异源加强比单剂量 Convidecia 更具免疫原性，并且不存在安全问题。这些结果支持病毒载体疫苗和重组蛋白疫苗合作的灵活性。重组COVID-19疫苗（Ad5载体）和基于RBD的蛋白亚基疫苗的异源初免-加强研究； ClinicalTrial.gov NCT04833101。在一项随机对照试验中，Pengfei Jin 及其同事评估了重组腺病毒 5 型载体 COVID-19 疫苗和基于蛋白质亚基的 COVID-19 疫苗异源免疫的安全性和免疫原性。随着针对严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的抗体减弱以及新变种的出现，2019 年冠状病毒病 (COVID-19) 疫苗的有效性随着时间的推移而下降，需要加强疫苗接种。本研究旨在评估重组腺病毒 5 型载体 COVID-19 疫苗 (Convidecia) 和基于蛋白质亚基的 COVID-19 疫苗 (ZF2001) 的异源免疫对于健康成人是否安全且具有免疫原性。已接受 1 剂 Convidecia 的 120 名参与者被随机分配 (2:1) 接受 1 剂 ZF2001 肌肉注射或安慰剂对照（三价灭活流感疫苗 (TIV)），在初免后 28 天或 56 天注射，并在第二次注射后 4 个月时接受第三次 ZF2001 注射。所有报告的不良反应都很轻微，最常见的不良反应是注射部位疼痛。 Convidecia 初次疫苗接种后的 ZF2001 异源方案可以诱导强烈的免疫反应，特别是在 5 至 6 个月的初免-加强间隔期间。这些数据支持使用 Convidecia 和 ZF2001 进行异源免疫。
Heterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored Coronavirus Disease 2019 (COVID-19) vaccine (Convidecia, hereafter referred to as CV) and a protein-subunit-based COVID-19 vaccine (ZF2001, hereafter referred to as ZF). We conducted a randomized, observer-blinded, placebo-controlled trial, in which healthy adults aged 18 years or older, who have received 1 dose of Convidecia, with no history of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, were recruited in Jiangsu, China. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or placebo control (trivalent inactivated influenza vaccine (TIV)) administered at 28 days after priming, and received the third injection with ZF2001 at 5 months, referred to as CV/ZF/ZF (D0-D28-M5) and CV/ZF (D0-M5) regimen, respectively. Sixty participants were randomly assigned (2:1) to receive either 1 dose of ZF2001 or TIV administered at 56 days after priming, and received the third injection with ZF2001 at 6 months, referred to as CV/ZF/ZF (D0-D56-M6) and CV/ZF (D0-M6) regimen, respectively. Participants and investigators were masked to the vaccine received but not to the boosting interval. Primary endpoints were the geometric mean titer (GMT) of neutralizing antibodies against wild-type SARS-CoV-2 and 7-day solicited adverse reactions. The primary analysis was done in the intention-to-treat population. Between April 7, 2021 and May 6, 2021, 120 eligible participants were randomly assigned to receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 28 days and 5 months post priming, and receive ZF2001/ZF2001 (n = 40) or TIV/ZF2001 (n = 20) 56 days and 6 months post priming. Of them, 7 participants did not receive the third injection with ZF2001. A total of 26 participants (21.7%) reported solicited adverse reactions within 7 days post boost vaccinations, and all the reported adverse reactions were mild, with 13 (32.5%) in CV/ZF/ZF (D0-D28-M5) regimen, 7 (35.0%) in CV/ZF (D0- M5) regimen, 4 (10.0%) in CV/ZF/ZF (D0-D56-M6) regimen, and 2 (10.0%) in CV/ZF (D0-M6) regimen, respectively. At 14 days post first boost, GMTs of neutralizing antibodies in recipients receiving ZF2001 at 28 days and 56 days post priming were 18.7 (95% CI 13.7 to 25.5) and 25.9 (17.0 to 39.3), respectively, with geometric mean ratios of 2.0 (1.2 to 3.5) and 3.4 (1.8 to 6.4) compared to TIV. GMTs at 14 days after second boost of neutralizing antibodies increased to 107.2 (73.7 to 155.8) in CV/ZF/ZF (D0-D28-M5) regimen and 141.2 (83.4 to 238.8) in CV/ZF/ZF (D0-D56-M6) regimen. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced antibody levels comparable with that elicited by 3-dose schedules, with GMTs of 90.5 (45.6, 179.8) and 94.1 (44.0, 200.9), respectively. Study limitations include the absence of vaccine effectiveness in a real-world setting and current lack of immune persistence data. Heterologous boosting with ZF2001 following primary vaccination with Convidecia is more immunogenic than a single dose of Convidecia and is not associated with safety concerns. These results support flexibility in cooperating viral vectored and recombinant protein vaccines. Study on Heterologous Prime-boost of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine; ClinicalTrial.gov NCT04833101. In a randomized controlled trial, Pengfei Jin and colleagues assess the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored COVID-19 vaccine and a protein-subunit-based COVID-19 vaccine. With the waning of antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) coinciding with the emergence of the new variants, the effectiveness of Coronavirus Disease 2019 (COVID-19) vaccines has declined over time, necessitating booster vaccinations. This study was performed to evaluate whether heterologous immunization with a recombinant adenovirus type-5-vectored COVID-19 vaccine (Convidecia) and a protein-subunit-based COVID-19 vaccine (ZF2001) was safe and immunogenic in healthy adults. One hundred twenty participants who have received 1 dose of Convidecia were randomly assigned (2:1) to receive either 1 intramuscular dose of ZF2001 or placebo control (trivalent inactivated influenza vaccine (TIV)), administered at either 28 days or 56 days after priming, and received the third injection with ZF2001 at 4 months after second dose. All the reported adverse reactions were mild, and the most common adverse reaction was injection-site pain. Heterologous schedules of ZF2001 following the primary vaccination of Convidecia can induce robust immune responses, particularly with a 5 to 6 months prime-boost interval. These data support the use of heterologous immunization with Convidecia and ZF2001.
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DOI：
10.1126/science.abm0620
发表时间：
2022-01-21
期刊：
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