PDF(Pubmed)
Abstract：
Here we conducted a multicenter open-label, randomized phase 2 and 3 study to assess the safety and immunogenicity of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-specific (BA.1/B.1.1.529), monovalent, thermostable, self-amplifying mRNA vaccine, GEMCOVAC-OM, when administered intradermally as a booster in healthy adults who had received two doses of BBV152 or ChAdOx1 nCoV-19. GEMCOVAC-OM was well tolerated with no related serious adverse events in both phase 2 and phase 3. In phase 2, the safety and immunogenicity of GEMCOVAC-OM was compared with our prototype mRNA vaccine GEMCOVAC-19 (D614G variant-specific) in 140 participants. At day 29 after vaccination, there was a significant rise in anti-spike (BA.1) IgG antibodies with GEMCOVAC-OM (P < 0.0001) and GEMCOVAC-19 (P < 0.0001). However, the IgG titers (primary endpoint) and seroconversion were higher with GEMCOVAC-OM (P < 0.0001). In phase 3, GEMCOVAC-OM was compared with ChAdOx1 nCoV-19 in 3,140 participants (safety cohort), which included an immunogenicity cohort of 420 participants. At day 29, neutralizing antibody titers against the BA.1 variant of SARS-CoV-2 were significantly higher than baseline in the GEMCOVAC-OM arm (P < 0.0001), but not in the ChAdOx1 nCoV-19 arm (P = 0.1490). GEMCOVAC-OM was noninferior (primary endpoint) and superior to ChAdOx1 nCoV-19 in terms of neutralizing antibody titers and seroconversion rate (lower bound 95% confidence interval of least square geometric mean ratio >1 and difference in seroconversion >0% for superiority). At day 29, anti-spike IgG antibodies and seroconversion (secondary endpoints) were significantly higher with GEMCOVAC-OM (P < 0.0001). These results demonstrate that GEMCOVAC-OM is safe and boosts immune responses against the B.1.1.529 variant. Clinical Trial Registry India identifier: CTRI/2022/10/046475 .
摘要：
在这里，我们进行了多中心开放标签，随机2期和3期研究，以评估严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）Omicron特异性（BA.1/B.1.1.529）的安全性和免疫原性，单价，热稳定，自扩增mRNA疫苗，GEMCOVAC-OM,当在接受两剂BBV152或ChAdOx1nCoV-19的健康成人中作为增强剂进行皮内给药时。GEMCOVAC-OM在2期和3期均具有良好的耐受性，没有相关的严重不良事件。在第2阶段，在140名参与者中，将GEMCOVAC-OM的安全性和免疫原性与我们的原型mRNA疫苗GEMCOVAC-19（D614G变体特异性）进行了比较。接种疫苗后第29天，使用GEMCOVAC-OM（P<0.0001）和GEMCOVAC-19（P<0.0001）的抗标（BA.1）IgG抗体显着升高。然而,GEMCOVAC-OM组的IgG滴度(主要终点)和血清转化率较高(P<0.0001).在第3阶段，在3,140名参与者（安全性队列）中，将GEMCOVAC-OM与ChAdOx1nCoV-19进行了比较，其中包括420名参与者的免疫原性队列。在第29天，在GEMCOVAC-OM臂中，针对SARS-CoV-2的BA.1变体的中和抗体滴度显着高于基线（P<0.0001），但在ChAdOx1nCoV-19臂中没有(P=0.1490)。GEMCOVAC-OM在中和抗体滴度和血清转换率方面不劣质（主要终点），并且优于ChAdOx1nCoV-19（最小二乘几何平均比率的下限95％置信区间>1，血清转换差异>0％为优势）。在第29天,GEMCOVAC-OM的抗尖峰IgG抗体和血清转化(次要终点)显著更高(P<0.0001)。这些结果证明GEMCOVAC-OM是安全的并且增强针对B.1.1.29变体的免疫应答。印度临床试验注册标识符：CTRI/2022/10/046475。
