Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial.
Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial.
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DOI：
10.1016/s1473-3099(20)30942-7
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发表时间：
2021-05
期刊：
影响因子：
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通讯作者：
Bhargava B
中科院分区：
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作者：
Ella R;Vadrevu KM;Jogdand H;Prasad S;Reddy S;Sarangi V;Ganneru B;Sapkal G;Yadav P;Abraham P;Panda S;Gupta N;Reddy P;Verma S;Kumar Rai S;Singh C;Redkar SV;Gillurkar CS;Kushwaha JS;Mohapatra S;Rao V;Guleria R;Ella K;Bhargava B
为了减轻新冠肺炎的影响，迫切需要一种疫苗。BBV152是一种全病毒粒子灭活SARS-CoV-2疫苗，由Toll样受体7/8激动剂分子吸附在明矾(ALGel-IMDG)或明矾(ALGel)上制成。我们在印度的11家医院进行了一项双盲、多中心、随机、对照的第1阶段试验，以评估BBV152的安全性和免疫原性。被调查者认为健康的18-55岁的健康成年人符合条件。SARS-CoV-2核酸和/或血清学检测阳性的个人被排除在外。参与者被随机分配到三种疫苗制剂中的一种(3μg和阿尔盖尔-IMDG、6μg和6μg和阿尔盖尔)或仅阿尔盖尔对照疫苗组。区组随机化是通过网络响应平台完成的。参与者和调查人员被蒙面进行治疗组分配。在第0天(随机当天)和第14天肌肉注射两次疫苗。主要结果是在接种疫苗后2小时和7天以及整个研究期间征集局部和全身反应性事件，包括严重不良事件。次要结果是基于野生型病毒中和的血清转换(至少是基线的四倍)。细胞内染色和ELISpot检测细胞介导的反应。该试验在ClinicalTrials.gov(NCT04471519)上注册。在2020年7月13日至30日期间，对827名参与者进行了筛选，其中375人入选。在登记的参与者中，100人被随机分配到三个疫苗组，75人被随机分配到对照组(仅限阿尔盖尔)。在两次剂量后，3μg联合阿尔盖尔-IMDG组有17例(17%；95%可信区间10·5~2 6·1)出现局部和全身不良反应，6μg联合阿尔盖尔-IMDG组21例(2 1%；13·8~30·5)，6μg联合阿尔盖尔组14例(14%；8·1~2 2·7)，单纯阿尔盖尔组10例(10%；6·9~2 3·6)。最常见的不良事件是注射部位疼痛(375名参与者中的17名[5%])、头痛(13名[3%])、疲劳(11名[3%])、发热(9名[2%])和恶心或呕吐(7名[2%])。所有征集的不良反应都是轻微的(43例[69%]62例)或中度的(19例[31%])，并且在第一次服药后更加频繁。在6μg联合阿尔盖尔组中报告了1例病毒性肺炎的严重不良事件，与疫苗无关。3μg组、6μg组和6μg组的血清转换率(%)分别为87·9、91·9和82·8。在来自阿尔盖尔-IMDG两组的16名参与者中检测到了CD4+和CD8+T细胞反应。BBV152导致了可耐受的安全结果和增强的免疫反应。这两种阿尔盖尔-IMDG制剂都被选为第二阶段免疫原性试验。进一步的疗效试验是有必要的。巴拉特生物技术国际公司。
To mitigate the effects of COVID-19, a vaccine is urgently needed. BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) or alum (Algel). We did a double-blind, multicentre, randomised, controlled phase 1 trial to assess the safety and immunogenicity of BBV152 at 11 hospitals across India. Healthy adults aged 18–55 years who were deemed healthy by the investigator were eligible. Individuals with positive SARS-CoV-2 nucleic acid and/or serology tests were excluded. Participants were randomly assigned to receive either one of three vaccine formulations (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) or an Algel only control vaccine group. Block randomisation was done with a web response platform. Participants and investigators were masked to treatment group allocation. Two intramuscular doses of vaccines were administered on day 0 (the day of randomisation) and day 14. Primary outcomes were solicited local and systemic reactogenicity events at 2 h and 7 days after vaccination and throughout the full study duration, including serious adverse events. Secondary outcome was seroconversion (at least four-fold increase from baseline) based on wild-type virus neutralisation. Cell-mediated responses were evaluated by intracellular staining and ELISpot. The trial is registered at ClinicalTrials.gov (NCT04471519). Between July 13 and 30, 2020, 827 participants were screened, of whom 375 were enrolled. Among the enrolled participants, 100 each were randomly assigned to the three vaccine groups, and 75 were randomly assigned to the control group (Algel only). After both doses, solicited local and systemic adverse reactions were reported by 17 (17%; 95% CI 10·5–26·1) participants in the 3 μg with Algel-IMDG group, 21 (21%; 13·8–30·5) in the 6 μg with Algel-IMDG group, 14 (14%; 8·1–22·7) in the 6 μg with Algel group, and ten (10%; 6·9–23·6) in the Algel-only group. The most common solicited adverse events were injection site pain (17 [5%] of 375 participants), headache (13 [3%]), fatigue (11 [3%]), fever (nine [2%]), and nausea or vomiting (seven [2%]). All solicited adverse events were mild (43 [69%] of 62) or moderate (19 [31%]) and were more frequent after the first dose. One serious adverse event of viral pneumonitis was reported in the 6 μg with Algel group, unrelated to the vaccine. Seroconversion rates (%) were 87·9, 91·9, and 82·8 in the 3 μg with Algel-IMDG, 6 μg with Algel-IMDG, and 6 μg with Algel groups, respectively. CD4+ and CD8+ T-cell responses were detected in a subset of 16 participants from both Algel-IMDG groups. BBV152 led to tolerable safety outcomes and enhanced immune responses. Both Algel-IMDG formulations were selected for phase 2 immunogenicity trials. Further efficacy trials are warranted. Bharat Biotech International.