Rose Winsley, Raju Reshma, Babji Sudhir, George Anna, Madhavan Ramya, Leander Xavier Julian Vivek, David Chelladurai Jenita Sharon, Nikitha Origanti Sharon, Deborah Arpitha Anbu, Vijayakumar Shalini, Immanuel Sushil, John Jacob, Rupali Priscilla, Abhilash Kundavaram P P, Mohan Venkata Raghava, Tallapaka Karthik Bharadwaj, Samuel Prasanna, Kang Gagandeep
Department of Pediatrics, Christian Medical College, Vellore, India.
The Wellcome Trust Research Laboratory, Christian Medical College, Vellore, India.
Lancet Reg Health Southeast Asia. 2023 Jan 24;12:100141. doi: 10.1016/j.lansea.2023.100141.
Primary SARS-CoV-2 vaccination has been shown to wane with time and provide lower protection from disease with new viral variants, prompting the WHO to recommend the administration of booster doses. We determined the safety and immunogenicity of homologous or heterologous boosters with ChAdOx1 nCoV-19 (COVISHIELD™) or BBV152 (COVAXIN®), the two vaccines used widely for primary immunization in India, in participants who had already received two primary doses of these vaccines.
Participants primed with two doses each of COVISHIELD™ or COVAXIN® 12-36 weeks previously, were randomised to receive either COVISHIELD™ or COVAXIN® booster in a 1:1 ratio. The primary outcome was day 28 post-booster anti-spike IgG seropositivity and secondary outcomes were anti-spike IgG levels and assessment of safety and reactogenicity. The results of 90 days intention-to-treat analysis are presented. This trial is registered with ISRCTN (CTRI/2021/08/035648).
In the COVISHIELD™ primed group with 200 participants, the seropositivity 28 days post booster in the heterologous COVAXIN® arm was 99% and non-inferior to the homologous COVISHIELD™ arm, which was also 99% (difference 0%; 95% CI: -2.8% to 2.7%). The geometric mean concentration (GMC) of anti-spike antibodies following heterologous COVAXIN® boost on day 28 was 36,190.78 AU/mL (95% CI: 30,526.64-42,905.88) while the GMC following homologous COVISHIELD™ boost was 97,445.09 AU/mL (82,626.97-114,920.7). In the COVAXIN® primed group with 204 participants, the seropositivity 28 days post booster in the heterologous COVISHIELD™ arm was 100% and non inferior to the homologous COVAXIN® arm which was 96% (difference 4%, 95% CI: 0.2%-7.8%). The GMC following heterologous COVISHIELD™ boost was 241,681.6 AU/mL (95% CI: 201,380.2-290,048.3) compared to homologous COVAXIN® boost, which was 48,473.94 AU/mL (95% CI: 38,529.56-60,984.95). The day 28 geometric mean ratio (GMR) of the anti-spike IgG between the heterologous and homologous boosted arms was 0.42 (95% CI: 0.34-0.52) in the COVISHIELD™ primed group and 5.11 (95% CI: 3.83-6.81) in the COVAXIN® primed group. There were no related serious adverse events reported in any group.
Homologous and heterologous boosting with COVISHIELD™ or COVAXIN® in COVISHIELD™ or COVAXIN® primed individuals are immunogenic and safe. A heterologous boost with COVISHIELD™ after COVAXIN® prime offers the best immune response among the four combinations evaluated.
Azim Premji Foundation and Bill and Melinda Gates Foundation.
原发性严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗接种效果会随时间减弱，且对新病毒变种提供的疾病防护较低，这促使世界卫生组织建议接种加强针。我们确定了在已接种两剂这两种疫苗进行初次免疫的参与者中，使用ChAdOx1 nCoV-19（COVISHIELD™）或BBV152（COVAXIN®）进行同源或异源加强针接种的安全性和免疫原性，这两种疫苗在印度广泛用于初次免疫。
在12 - 36周前已接种两剂COVISHIELD™或COVAXIN®的参与者，以1:1的比例随机接受COVISHIELD™或COVAXIN®加强针。主要结局是加强针接种后第28天抗刺突蛋白IgG血清学阳性，次要结局是抗刺突蛋白IgG水平以及安全性和反应原性评估。呈现了90天意向性分析结果。该试验已在国际标准随机对照试验编号注册系统（ISRCTN）注册（CTRI/2021/08/035648）。
在有200名参与者的COVISHIELD™初免组中，异源COVAXIN®组加强针接种后第28天的血清学阳性率为99%，不劣于同源COVISHIELD™组（同源组也为99%；差异0%；95%置信区间：-2.8%至2.7%）。异源COVAXIN®加强针接种后第28天抗刺突抗体的几何平均浓度（GMC）为36,190.78 AU/mL（95%置信区间：30,526.64 - 42,905.88），而同源COVISHIELD™加强针接种后的GMC为97,445.09 AU/mL（82,626.97 - 114,920.7）。在有204名参与者的COVAXIN®初免组中，异源COVISHIELD™组加强针接种后第28天的血清学阳性率为100%，不劣于同源COVAXIN®组（同源组为96%；差异4%，95%置信区间：0.2% - 7.8%）。异源COVISHIELD™加强针接种后的GMC为241,681.6 AU/mL（95%置信区间：201,380.2 - 290,048.3），相比之下同源COVAXIN®加强针接种后的GMC为48,473.94 AU/mL（95%置信区间：38,529.56 - 60,984.95）。在COVISHIELD™初免组中，异源和同源加强针组之间抗刺突蛋白IgG在第28天的几何平均比值（GMR）为0.42（95%置信区间：0.34 - 0.52），在COVAXIN®初免组中为5.11（95%置信区间：3.83 - 6.81）。任何组均未报告相关严重不良事件。
在COVISHIELD™或COVAXIN®初免个体中，使用COVISHIELD™或COVAXIN®进行同源和异源加强针接种具有免疫原性且安全。在评估的四种组合中，COVAXIN®初免后使用COVISHIELD™进行异源加强针接种可提供最佳免疫反应。
阿齐姆·普莱姆基基金会和比尔及梅琳达·盖茨基金会。
