Abstract：
The recurrent COVID-19 infection, despite global vaccination, highlights the need for booster doses. A heterologous booster has been suggested to enhance immunity and protection against emerging variants of concern of the SARS-CoV-2 virus. In this report, we aimed to assess the safety, and immunogenicity of COReNAPCIN, as a fourth booster dose after three doses of inactivated vaccines.
METHODS: The study was conducted as a double-blind, randomized, placebo-controlled phase 1 clinical trial of the mRNA-based vaccine candidate, COReNAPCIN. The vaccine was injected as a heterologous booster in healthy Iranian adults aged 18-50 who had previously received three doses of inactivated SARS-CoV-2 vaccines. In the study, 30 participants were randomly assigned to receive either COReNAPCIN in two different doses (25 µg and 50 µg) or placebo. The vaccine candidate contained mRNA encoding the complete sequence of the pre-fusion stabilized Spike protein of SARS-CoV-2, formulated within lipid nanoparticles. The primary endpoint was safety and the secondary objective was humoral immunogenicity until 6 months post-vaccination. The cellular immunogenicity was pursued as an exploratory outcome.
RESULTS: COReNAPCIN was well tolerated in vaccinated individuals in both doses with no life-threatening or other serious adverse events. The most noticeable solicited adverse events were pain at the site of injection, fatigue and myalgia. Regarding the immunogenicity, despite the seroprevalence of SARS-CoV-2 antibodies due to the vaccination history for all and previous SARS-CoV-2 infection for some participants, the recipients of 25 and 50 µg COReNAPCIN, two weeks post-vaccination, showed 6·6 and 8·1 fold increase in the level of anti-RBD, and 11·5 and 21·7 fold increase in the level of anti-spike antibody, respectively. The geometric mean virus neutralizing titers reached 10.2 fold in the 25 µg group and 8.4 fold in 50 µg group of pre-boost levels. After 6 months, the measured anti-spike antibody concentration still maintains a geometric mean fold rise of 2.8 and 6.3, comparing the baseline levels in 25 and 50 µg groups, respectively. Additionally, the significant increase in the spike-specific IFN-ϒ T-cell response upon vaccination underscores the activation of cellular immunity.
CONCLUSIONS: COReNAPCIN booster showed favorable safety, tolerability, and immunogenicity profile, supporting its further clinical development (Trial registration: IRCT20230131057293N1).
METHODS: The study was conducted as a double-blind, randomized, placebo-controlled phase 1 clinical trial of the mRNA-based vaccine candidate, COReNAPCIN. The vaccine was injected as a heterologous booster in healthy Iranian adults aged 18-50 who had previously received three doses of inactivated SARS-CoV-2 vaccines. In the study, 30 participants were randomly assigned to receive either COReNAPCIN in two different doses (25 µg and 50 µg) or placebo. The vaccine candidate contained mRNA encoding the complete sequence of the pre-fusion stabilized Spike protein of SARS-CoV-2, formulated within lipid nanoparticles. The primary endpoint was safety and the secondary objective was humoral immunogenicity until 6 months post-vaccination. The cellular immunogenicity was pursued as an exploratory outcome.
RESULTS: COReNAPCIN was well tolerated in vaccinated individuals in both doses with no life-threatening or other serious adverse events. The most noticeable solicited adverse events were pain at the site of injection, fatigue and myalgia. Regarding the immunogenicity, despite the seroprevalence of SARS-CoV-2 antibodies due to the vaccination history for all and previous SARS-CoV-2 infection for some participants, the recipients of 25 and 50 µg COReNAPCIN, two weeks post-vaccination, showed 6·6 and 8·1 fold increase in the level of anti-RBD, and 11·5 and 21·7 fold increase in the level of anti-spike antibody, respectively. The geometric mean virus neutralizing titers reached 10.2 fold in the 25 µg group and 8.4 fold in 50 µg group of pre-boost levels. After 6 months, the measured anti-spike antibody concentration still maintains a geometric mean fold rise of 2.8 and 6.3, comparing the baseline levels in 25 and 50 µg groups, respectively. Additionally, the significant increase in the spike-specific IFN-ϒ T-cell response upon vaccination underscores the activation of cellular immunity.
CONCLUSIONS: COReNAPCIN booster showed favorable safety, tolerability, and immunogenicity profile, supporting its further clinical development (Trial registration: IRCT20230131057293N1).
摘要：
复发性COVID-19感染，尽管全球疫苗接种，强调了加强剂量的需要。已经提出了一种异源加强剂,以增强对SARS-CoV-2病毒的新出现的变体的免疫力和保护作用。在这份报告中,我们的目的是评估安全性，和CORENAPCIN的免疫原性，作为三剂灭活疫苗后的第四剂加强剂量。
方法：该研究是以双盲，随机化，基于mRNA的候选疫苗的安慰剂对照1期临床试验，CORENAPCIN.该疫苗作为异源加强剂注射到18-50岁的健康伊朗成年人中，这些成年人以前曾接受过三剂灭活的SARS-CoV-2疫苗。在研究中,30名参与者被随机分配接受两种不同剂量（25µg和50µg）的COReNAPCIN或安慰剂。候选疫苗包含编码SARS-CoV-2的融合前稳定的Spike蛋白的完整序列的mRNA,其配制在脂质纳米颗粒内。主要终点是安全性，次要目标是直到接种后6个月的体液免疫原性。追求细胞免疫原性作为探索性结果。
结果：COReNAPCIN在两种剂量的接种个体中均具有良好的耐受性，没有危及生命或其他严重不良事件。最明显的不良事件是注射部位疼痛，疲劳和肌痛。关于免疫原性，尽管SARS-CoV-2抗体的血清阳性率是由于所有的疫苗接种史和一些参与者以前的SARS-CoV-2感染，25和50µgCORENAPCIN的接受者，接种疫苗两周后，显示抗RBD水平增加6·6和8·1倍，抗刺突抗体水平增加11·5和21·7倍，分别。几何平均病毒中和滴度在25µg组中达到10.2倍，在50µg预加强水平组中达到8.4倍。六个月后,与25和50µg组的基线水平相比，测得的抗尖峰抗体浓度仍保持2.8和6.3的几何平均倍数上升，分别。此外,疫苗接种后,特异性IFN-γT细胞应答的显著增加强调了细胞免疫的激活.
结论：COReNAPCIN加强剂显示良好的安全性，耐受性,和免疫原性概况，支持其进一步的临床开发（试验注册：IRCT20230131057293N1）。
方法：该研究是以双盲，随机化，基于mRNA的候选疫苗的安慰剂对照1期临床试验，CORENAPCIN.该疫苗作为异源加强剂注射到18-50岁的健康伊朗成年人中，这些成年人以前曾接受过三剂灭活的SARS-CoV-2疫苗。在研究中,30名参与者被随机分配接受两种不同剂量（25µg和50µg）的COReNAPCIN或安慰剂。候选疫苗包含编码SARS-CoV-2的融合前稳定的Spike蛋白的完整序列的mRNA,其配制在脂质纳米颗粒内。主要终点是安全性，次要目标是直到接种后6个月的体液免疫原性。追求细胞免疫原性作为探索性结果。
结果：COReNAPCIN在两种剂量的接种个体中均具有良好的耐受性，没有危及生命或其他严重不良事件。最明显的不良事件是注射部位疼痛，疲劳和肌痛。关于免疫原性，尽管SARS-CoV-2抗体的血清阳性率是由于所有的疫苗接种史和一些参与者以前的SARS-CoV-2感染，25和50µgCORENAPCIN的接受者，接种疫苗两周后，显示抗RBD水平增加6·6和8·1倍，抗刺突抗体水平增加11·5和21·7倍，分别。几何平均病毒中和滴度在25µg组中达到10.2倍，在50µg预加强水平组中达到8.4倍。六个月后,与25和50µg组的基线水平相比，测得的抗尖峰抗体浓度仍保持2.8和6.3的几何平均倍数上升，分别。此外,疫苗接种后,特异性IFN-γT细胞应答的显著增加强调了细胞免疫的激活.
结论：COReNAPCIN加强剂显示良好的安全性，耐受性,和免疫原性概况，支持其进一步的临床开发（试验注册：IRCT20230131057293N1）。
