Abstract：
BACKGROUND: Inactivated whole-virus vaccination elicits immune responses to both SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, like natural infections. A heterologous Ad26.COV2.S booster given at two different intervals after primary BBIBP-CorV vaccination was safe and immunogenic at days 28 and 84, with higher immune responses observed after the longer pre-boost interval. We describe booster-specific and hybrid immune responses over 1 year.
METHODS: This open-label phase 1/2 study was conducted in healthy Thai adults aged ≥ 18 years who had completed primary BBIBP-CorV primary vaccination between 90-240 (Arm A1; n = 361) or 45-75 days (Arm A2; n = 104) before enrolment. All received an Ad26.COV2.S booster. We measured anti-S and anti-N IgG antibodies by Elecsys®, neutralizing antibodies by SARS-CoV-2 pseudovirus neutralization assay, and T-cell responses by quantitative interferon (IFN)-γ release assay. Immune responses were evaluated in the baseline-seronegative population (pre-booster anti-N < 1.4 U/mL; n = 241) that included the booster-effect subgroup (anti-N < 1.4 U/mL at each visit) and the hybrid-immunity subgroup (anti-N ≥ 1.4 U/mL and/or SARS-CoV-2 infection, irrespective of receiving non-study COVID-19 boosters).
RESULTS: In Arm A1 of the booster-effect subgroup, anti-S GMCs were 131-fold higher than baseline at day 336; neutralizing responses against ancestral SARS-CoV-2 were 5-fold higher than baseline at day 168; 4-fold against Omicron BA.2 at day 84. IFN-γ remained approximately 4-fold higher than baseline at days 168 and 336 in 18-59-year-olds. Booster-specific responses trended lower in Arm A2. In the hybrid-immunity subgroup at day 336, anti-S GMCs in A1 were 517-fold higher than baseline; neutralizing responses against ancestral SARS-CoV-2 and Omicron BA.2 were 28- and 31-fold higher, respectively, and IFN-γ was approximately 14-fold higher in 18-59-year-olds at day 336. Durable immune responses trended lower in ≥ 60-year-olds.
CONCLUSIONS: A heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination induced booster-specific immune responses detectable up to 1 year that were higher in participants with hybrid immunity.
BACKGROUND: NCT05109559.
METHODS: This open-label phase 1/2 study was conducted in healthy Thai adults aged ≥ 18 years who had completed primary BBIBP-CorV primary vaccination between 90-240 (Arm A1; n = 361) or 45-75 days (Arm A2; n = 104) before enrolment. All received an Ad26.COV2.S booster. We measured anti-S and anti-N IgG antibodies by Elecsys®, neutralizing antibodies by SARS-CoV-2 pseudovirus neutralization assay, and T-cell responses by quantitative interferon (IFN)-γ release assay. Immune responses were evaluated in the baseline-seronegative population (pre-booster anti-N < 1.4 U/mL; n = 241) that included the booster-effect subgroup (anti-N < 1.4 U/mL at each visit) and the hybrid-immunity subgroup (anti-N ≥ 1.4 U/mL and/or SARS-CoV-2 infection, irrespective of receiving non-study COVID-19 boosters).
RESULTS: In Arm A1 of the booster-effect subgroup, anti-S GMCs were 131-fold higher than baseline at day 336; neutralizing responses against ancestral SARS-CoV-2 were 5-fold higher than baseline at day 168; 4-fold against Omicron BA.2 at day 84. IFN-γ remained approximately 4-fold higher than baseline at days 168 and 336 in 18-59-year-olds. Booster-specific responses trended lower in Arm A2. In the hybrid-immunity subgroup at day 336, anti-S GMCs in A1 were 517-fold higher than baseline; neutralizing responses against ancestral SARS-CoV-2 and Omicron BA.2 were 28- and 31-fold higher, respectively, and IFN-γ was approximately 14-fold higher in 18-59-year-olds at day 336. Durable immune responses trended lower in ≥ 60-year-olds.
CONCLUSIONS: A heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination induced booster-specific immune responses detectable up to 1 year that were higher in participants with hybrid immunity.
BACKGROUND: NCT05109559.
摘要：
背景：灭活的全病毒疫苗可引发对SARS-CoV-2核衣壳（N）和刺突（S）蛋白的免疫反应，比如自然感染.一种异源Ad26。COV2.在初次BBIBP-CorV疫苗接种后在两个不同间隔给予的S加强剂在第28天和第84天是安全和免疫原性的,在更长的预加强间隔后观察到更高的免疫应答。我们描述了超过1年的加强特异性和混合免疫反应。
方法：这项开放标签1/2期研究是在18岁以上的健康泰国成年人中进行的，他们在招募前90-240天（A1组；n=361）或45-75天（A2组；n=104）完成了BBIBP-CorV初次疫苗接种。所有人都收到了Ad26。COV2.S助推器。我们通过Elecsys®测量了抗S和抗NIgG抗体，SARS-CoV-2假病毒中和试验中和抗体，通过定量干扰素（IFN）-γ释放测定和T细胞反应。在基线血清阴性人群（加强前的抗N<1.4U/mL;n=241）中评估了免疫反应，包括加强效应亚组（每次就诊时抗N<1.4U/mL）和混合免疫亚组（抗N≥1.4U/mL和/或SARS-CoV-2感染，无论是否接受非研究型COVID-19助推器)。
结果：在增强效应亚组的A1组中，第336天抗SGMC比基线高131倍;第168天抗祖先SARS-CoV-2的中和反应比基线高5倍;第84天抗OmicronBA.2的中和反应比基线高4倍.在18-59岁的青少年中,在第168天和第336天,IFN-γ仍然比基线高约4倍。在A2组中，特定于增强剂的反应趋势较低。在第336天的杂交免疫亚组中，A1中的抗SGMC比基线高517倍；针对祖先SARS-CoV-2和OmicronBA.2的中和反应分别高28倍和31倍，分别,在第336天，18-59岁的儿童中IFN-γ约为14倍。在≥60岁的人群中，持久的免疫反应呈下降趋势。
结论：异源Ad26。COV2.初次BBIBP-CorV疫苗接种后的S加强剂诱导的加强剂特异性免疫反应可检测到长达1年，在具有混合免疫的参与者中更高。
背景：NCT05109559。
方法：这项开放标签1/2期研究是在18岁以上的健康泰国成年人中进行的，他们在招募前90-240天（A1组；n=361）或45-75天（A2组；n=104）完成了BBIBP-CorV初次疫苗接种。所有人都收到了Ad26。COV2.S助推器。我们通过Elecsys®测量了抗S和抗NIgG抗体，SARS-CoV-2假病毒中和试验中和抗体，通过定量干扰素（IFN）-γ释放测定和T细胞反应。在基线血清阴性人群（加强前的抗N<1.4U/mL;n=241）中评估了免疫反应，包括加强效应亚组（每次就诊时抗N<1.4U/mL）和混合免疫亚组（抗N≥1.4U/mL和/或SARS-CoV-2感染，无论是否接受非研究型COVID-19助推器)。
结果：在增强效应亚组的A1组中，第336天抗SGMC比基线高131倍;第168天抗祖先SARS-CoV-2的中和反应比基线高5倍;第84天抗OmicronBA.2的中和反应比基线高4倍.在18-59岁的青少年中,在第168天和第336天,IFN-γ仍然比基线高约4倍。在A2组中，特定于增强剂的反应趋势较低。在第336天的杂交免疫亚组中，A1中的抗SGMC比基线高517倍；针对祖先SARS-CoV-2和OmicronBA.2的中和反应分别高28倍和31倍，分别,在第336天，18-59岁的儿童中IFN-γ约为14倍。在≥60岁的人群中，持久的免疫反应呈下降趋势。
结论：异源Ad26。COV2.初次BBIBP-CorV疫苗接种后的S加强剂诱导的加强剂特异性免疫反应可检测到长达1年，在具有混合免疫的参与者中更高。
背景：NCT05109559。
