Institute of Virology, Department of Hygiene, Microbiology and Public Health, Medical University of Innsbruck, Peter-Mayr-Str. 4b, 6020 Innsbruck, Austria.
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
EBioMedicine. 2022 Jun;80:104073. doi: 10.1016/j.ebiom.2022.104073. Epub 2022 May 23.
Several COVID-19 vaccines have been approved. The mRNA vaccine from Pfizer/BioNTech (Comirnaty, BNT162b2; BNT) and the vector vaccine from AstraZeneca (Vaxzevria, ChAdOx1; AZ) have been widely used. mRNA vaccines induce high antibody and T cell responses, also to SARS-CoV-2 variants, but are costlier and less stable than the slightly less effective vector vaccines. For vector vaccines, heterologous vaccination schedules have generally proven more effective than homologous schedules.
In the HEVACC three-arm, single-blinded, adaptive design study (ClinicalTrials.gov Identifier: NCT04907331), participants between 18 and 65 years with no prior history of SARS-CoV-2 infection and a first dose of AZ or BNT were included. The AZ/AZ and the AZ/BNT arms were randomized (in a 1:1 ratio stratified by sex and trial site) and single-blinded, the third arm (BNT/BNT) was observational. We compared the reactogenicity between the study arms and hypothesized that immunogenicity was higher for the heterologous AZ/BNT compared to the homologous AZ/AZ regimen using neutralizing antibody titers as primary endpoint.
This interim analysis was conducted after 234 participants had been randomized and 254 immunized (N=109 AZ/AZ, N=115 AZ/BNZ, N=30 BNT/BNT). Heterologous AZ/BNT vaccination was well tolerated without study-related severe adverse events. Neutralizing antibody titers on day 30 were statistically significant higher in the AZ/BNT and the BNT/BNT groups than in the AZ/AZ group, for B.1.617.2 (Delta) AZ/AZ median reciprocal titer 75.9 (99.9% CI 58.0 - 132.5), AZ/BNT 571.5 (99.9% CI 396.6 - 733.1), and BNT/BNT 404.5 (99.9% CI 68.3 - 1024). Similarly, the frequency and multifunctionality of spike-specific T cell responses was comparable between the AZ/BNT and the BNT/BNT groups, but lower in the AZ/AZ vaccinees.
This study clearly shows the immunogenicity and safety of heterologous AZ/BNT vaccination and encourages further studies on heterologous vaccination schedules.
This work was supported by the Medical University of Innsbruck, and partially funded by NIAID contracts No. 75N9301900065, 75N93021C00016, and 75N93019C00051.
已有几种 COVID-19 疫苗获得批准。辉瑞/生物新技术公司（Pfizer/BioNTech）的 mRNA 疫苗（Comirnaty，BNT162b2；BNT）和阿斯利康（AstraZeneca）的载体疫苗（Vaxzevria，ChAdOx1；AZ）已广泛使用。mRNA 疫苗可诱导高抗体和 T 细胞反应，对 SARS-CoV-2 变体也是如此，但成本更高且稳定性低于稍低效的载体疫苗。对于载体疫苗，异源疫苗接种方案通常比同源疫苗接种方案更有效。
在 HEVACC 三臂、单盲、适应性设计研究（ClinicalTrials.gov 标识符：NCT04907331）中，纳入了年龄在 18 至 65 岁之间、无 SARS-CoV-2 感染史且已接种第一剂 AZ 或 BNT 的参与者。AZ/AZ 和 AZ/BNT 臂进行随机分组（按性别和试验地点分层 1:1 比例）并进行单盲，第三臂（BNT/BNT）为观察性。我们比较了研究臂之间的反应原性，并假设使用中和抗体滴度作为主要终点，异源 AZ/BNT 的免疫原性高于同源 AZ/AZ 方案。
在 234 名参与者被随机分组和 254 名参与者接种疫苗（N=109 AZ/AZ，N=115 AZ/BNZ，N=30 BNT/BNT）后进行了这项中期分析。异源 AZ/BNT 疫苗接种耐受性良好，无与研究相关的严重不良事件。第 30 天的中和抗体滴度在 AZ/BNT 和 BNT/BNT 组明显高于 AZ/AZ 组，对于 B.1.617.2（Delta）AZ/AZ 中位数倒数滴度为 75.9（99.9%CI 58.0-132.5），AZ/BNT 为 571.5（99.9%CI 396.6-733.1），BNT/BNT 为 404.5（99.9%CI 68.3-1024）。同样，刺突特异性 T 细胞反应的频率和多功能性在 AZ/BNT 和 BNT/BNT 组之间相当，但在 AZ/AZ 疫苗接种者中较低。
这项研究清楚地表明了异源 AZ/BNT 疫苗接种的免疫原性和安全性，并鼓励进一步研究异源疫苗接种方案。
这项工作得到了因斯布鲁克医科大学的支持，并部分由 NIAID 合同 No. 75N9301900065、75N93021C00016 和 75N93019C00051 资助。
