Kulkarni Prasad S, Padmapriyadarsini Chandrasekaran, Vekemans Johan, Bavdekar Ashish, Gupta Madhu, Kulkarni Praveen, Garg B S, Gogtay Nithya J, Tambe Muralidhar, Lalwani Sanjay, Singh Kiranjit, Munshi Renuka, Meshram Sushant, Selvavinayagam T S, Pandey Krishna, Bhimarasetty Devi Madhavi, Ramakrishnan S R, Bhamare Chetanraj, Dharmadhikari Abhijeet, Vadakkedath Rajeev, Bonhomme Cyrille J, Thakar Madhuri, Kurle Swarali N, Kelly Elizabeth J, Gautam Manish, Gupta Nivedita, Panda Samiran, Bhargava Balram, Shaligram Umesh, Kapse Dhananjay, Gunale Bhagwat
Serum Institute of India Pvt Ltd, Pune, India.
Indian Council of Medical Research, Delhi, India.
EClinicalMedicine. 2021 Dec;42:101218. doi: 10.1016/j.eclinm.2021.101218. Epub 2021 Nov 30.
This phase 2/3 immunobridging study evaluated the safety and immunogenicity of the ChAdOx1 nCoV-19 Coronavirus Vaccine (Recombinant) (SII-ChAdOx1 nCoV-19), manufactured in India at the Serum Institute of India Pvt Ltd (SIIPL), following technology transfer from the AstraZeneca.
This participant-blind, observer-blind study randomised participants 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (ChAdOx1 nCoV-19) (immunogenicity/reactogenicity cohort) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort). The study participants were enrolled from 14 hospitals across India between August 25 and October 31, 2020. Two doses of study products were given 4 weeks apart. The primary objectives were to demonstrate non-inferiority of SII-ChAdOx1 nCoV-19 to AZD1222 in terms of geometric mean titre (GMT) ratio of anti-SARS-CoV-2 spike IgG antibodies 28 days after the second dose (defined as lower limit of 95% CI >0·67) and to determine the incidence of serious adverse events (SAEs) causally related to SII-ChAdOx1 nCoV-19. The anti-spike IgG response was assessed using a multiplexed electrochemiluminescence-based immunoassay. Safety follow-up continued until 6 months after first dose. Trial registration: CTRI/2020/08/027170.
1601 participants were enrolled: 401 to the immunogenicity/reactogenicity cohort and 1200 to the safety cohort. After two doses, seroconversion rates for anti-spike IgG antibodies were more than 98·0% in both the groups. SII-ChAdOx1 nCoV-19 was non-inferior to AZD1222 (GMT ratio 0·98; 95% CI 0·78-1·23). SAEs were reported in ≤ 2·0% participants across the three groups; none were causally related. A total of 34 SARS-CoV-2 infections were reported; of which 6 occurred more than 2 weeks after the second dose; none were severe.
SII-ChAdOx1 nCoV-19 has a non-inferior immune response compared to AZD1222 and an acceptable safety/reactogenicity profile. Pharmacovigilance should be maintained to detect any safety signals.
SIIPL funded the contract research organisation and laboratory costs, while the site costs were funded by the Indian Council of Medical Research. The study vaccines were supplied by SIIPL and AstraZeneca.
这项2/3期免疫桥接研究评估了由印度血清研究所私人有限公司（SIIPL）在从阿斯利康进行技术转让后于印度生产的ChAdOx1 nCoV-19冠状病毒疫苗（重组）（SII-ChAdOx1 nCoV-19）的安全性和免疫原性。
这项参与者盲法、观察者盲法研究将参与者按3:1随机分配至SII-ChAdOx1 nCoV-19或AZD1222（ChAdOx1 nCoV-19）（免疫原性/反应原性队列），并按3:1随机分配至SII-ChAdOx1 nCoV-19或安慰剂（安全性队列）。研究参与者于2020年8月25日至10月31日期间从印度各地的14家医院招募。两剂研究产品间隔4周给药。主要目标是在第二剂后28天，证明SII-ChAdOx1 nCoV-19在抗SARS-CoV-2刺突IgG抗体的几何平均滴度（GMT）比值方面不劣于AZD1222（定义为95%置信区间下限>0·67），并确定与SII-ChAdOx1 nCoV-19有因果关系的严重不良事件（SAE）的发生率。使用基于多重电化学发光的免疫测定法评估抗刺突IgG反应。安全性随访持续至首剂后6个月。试验注册号：CTRI/2020/08/027170。
共招募了1601名参与者：401名进入免疫原性/反应原性队列，1200名进入安全性队列。两剂接种后，两组抗刺突IgG抗体的血清转化率均超过98·0%。SII-ChAdOx1 nCoV-19不劣于AZD1222（GMT比值0·98；95%置信区间0·78 - 1·23）。三组中报告SAE的参与者均≤2·0%；均无因果关系。共报告了34例SARS-CoV-2感染；其中6例发生在第二剂后2周以上；均不严重。
与AZD1222相比，SII-ChAdOx1 nCoV-19具有不劣的免疫反应，且安全性/反应原性特征可接受。应持续进行药物警戒以检测任何安全信号。
SIIPL资助了合同研究组织和实验室费用，而现场费用由印度医学研究理事会资助。研究疫苗由SIIPL和阿斯利康提供。
