Ahmed Tousief Irshad, Rishi Saqib, Irshad Summaiya, Aggarwal Jyoti, Happa Karan, Mansoor Sheikh
Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, JK, India.
Department of Microbiology, Government Medical College, Srinagar, JK, India.
Front Immunol. 2022 Aug 9;13:863162. doi: 10.3389/fimmu.2022.863162. eCollection 2022.
We systematically reviewed and summarized studies focusing on Bharat Biotech's Whole Virion Inactivated Corona Virus Antigen BBV152 (Covaxin), which is India's indigenous response to fighting the SARS-CoV-2 pandemic. Studies were searched for data on the efficacy, immunogenicity, and safety profile of BBV152. All relevant studies published up to March 22, 2022, were screened from major databases, and 25 studies were eventually inducted into the systematic review. The studies focused on the virus antigen (6 μg) adjuvanted with aluminium hydroxide gel and/or Imidazo quinolin gallamide (IMDG), aTLR7/8 agonist. Pre-clinical, phase I, and II clinical trials showed appreciable immunogenicity. Both neutralizing and binding antibody titers were significant and T cell responses were Th1-biased. Phase III trials on the 6 μg +Algel-IMDG formulation showed a 93.4% efficacy against severe COVID-19. Data from the trials revealed an acceptable safety profile with mostly mild-moderate local and systemic adverse events. No serious adverse events or fatalities were seen, and most studies reported milder and lesser adverse events with Covaxin when compared with other vaccines, especially Oxford-Astra Zeneca's AZD1222 (Covishield). The immunogenicity performance of Covaxin, which provided significant protection only after the second dose, was mediocre and it was consistently surpassed by Covishield. One study reported adjusted effectiveness against symptomatic infection to be just 50% at 2 weeks after the second dose. Nonetheless, appreciable results were seen in previously infected individuals administered both doses. There was some evidence of coverage against the Alpha, Beta, and Delta variants. However, neither Covaxin nor Covishield showed sufficient protection against the Omicron variant. Two studies reported super-additive results on mixing Covaxin with Covishield. Further exploration of heterologous prime-boost vaccination with a combination of an inactivated vaccine and an adenoviral vector-based vaccine for tackling future variants may be beneficial.
我们系统地回顾并总结了聚焦于巴拉特生物技术公司的全病毒灭活冠状病毒抗原BBV152（科瓦克辛）的研究，这是印度应对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行的本土举措。检索各项研究以获取关于BBV152的疗效、免疫原性和安全性的数据。从各大数据库中筛选截至2022年3月22日发表的所有相关研究，最终有25项研究被纳入该系统评价。这些研究聚焦于佐以氢氧化铝凝胶和/或咪唑喹啉没食子酰胺（IMDG，一种Toll样受体7/8激动剂）的病毒抗原（6微克）。临床前、I期和II期临床试验显示出可观的免疫原性。中和抗体滴度和结合抗体滴度均显著，且T细胞反应以Th1为主。对6微克+Algel-IMDG配方进行的III期试验显示，其对重症2019冠状病毒病（COVID-19）的疗效为93.4%。试验数据显示其安全性可接受，主要为轻度至中度的局部和全身不良事件。未观察到严重不良事件或死亡病例，且与其他疫苗（尤其是牛津-阿斯利康的AZD1222，即科维希尔德）相比，大多数研究报告称科瓦克辛的不良事件更轻微、更少。科瓦克辛的免疫原性表现一般，仅在第二剂接种后才提供显著保护，且一直被科维希尔德超越。一项研究报告称，在第二剂接种后2周，其对有症状感染的校正有效性仅为50%。尽管如此，在接受两剂接种的既往感染者中观察到了可观的结果。有一些证据表明其对阿尔法、贝塔和德尔塔变异株有一定的覆盖效果。然而，科瓦克辛和科维希尔德对奥密克戎变异株均未显示出足够的保护作用。两项研究报告了将科瓦克辛与科维希尔德混合使用的超加性结果。进一步探索使用灭活疫苗和基于腺病毒载体的疫苗组合进行异源初免-加强接种以应对未来变异株可能是有益的。
