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斯里兰卡个体中不同剂量间隔的AZD1222/Covishield疫苗免疫反应动力学

Kinetics of immune responses to the AZD1222/Covishield vaccine with varying dose intervals in Sri Lankan individuals.

作者信息

Jeewandara Chandima, Aberathna Inoka Sepali, Gomes Laksiri, Pushpakumara Pradeep Darshana, Danasekara Saubhagya, Guruge Dinuka, Ranasinghe Thushali, Gunasekera Banuri, Kamaladasa Achala, Kuruppu Heshan, Somathilake Gayasha, Dissanayake Osanda, Gamalath Nayanathara, Ekanayake Dinithi, Jayamali Jeewantha, Jayathilaka Deshni, Mudunkotuwa Anushika, Harvie Michael, Nimasha Thashmi, Wijayamuni Ruwan, Schimanski Lisa, Rijal Pramila, Tan Tiong K, Dong Tao, Townsend Alain, Ogg Graham S, Malavige Gathsaurie Neelika

机构信息

Allergy Immunology and Cell Biology Unit, Department of Immunology and Molecular Medicine, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.

Colombo Municipal Council, Colombo, Sri Lanka.

出版信息

medRxiv. 2021 Oct 27:2021.10.27.21265561. doi: 10.1101/2021.10.27.21265561.

Abstract

BACKGROUND

To understand the kinetics of immune responses with different dosing gaps of the AZD1222 vaccine, we compared antibody and T cell responses in two cohorts with two different dosing gaps.

METHODS

Antibodies to the SARS-CoV-2 virus were assessed in 297 individuals with a dosing gap of 12 weeks, sampled at 12 weeks post second dose (cohort 1) and in 77 individuals with a median dosing gap of 21.4 weeks (cohort 2) sampled 6 weeks post second dose. ACE2 receptor blocking antibodies (ACE2R-Abs), antibodies to the receptor binding domain (RBD) of the virus and variants of concern (VOC) and ex vivo T cell responses were assessed in a sub cohort.

RESULTS

All individuals (100%) had SARS-CoV-2 specific total antibodies and 94.2% of cohort 1 and 97.1% of cohort 2 had ACE2R-blocking Abs. There was no difference in antibody titres or positivity rates in different age groups in both cohorts. The ACE2R-blocking Abs (p<0.0001) and antibodies to the RBD of the VOCs were significantly higher in cohort 2, compared to cohort 1. 41.2% to 65.8% of different age groups gave a positive response by the haemagglutination assay to the RBD of the ancestral virus and VOCs in cohort 1, while 53.6% to 90% gave a positive response in cohort 2. 17/57 (29.8%) of cohort 1 and 17/29 (58.6%) of cohort 2 had ex vivo IFNγ ELISpot responses above the positive threshold. The ACE2R-blocking antibodies and ex vivo IFNγ ELISpot responses at 12 weeks post-first dose, significantly correlated with levels 12 weeks post second dose (Spearman's r=0.46, p=0.008) and (Spearman's r=0.71, p<0.0001) respectively.

CONCLUSIONS

Both dosing schedules resulted in high levels of antibody and T cell responses post vaccination, although those with a longer dosing gap had a higher magnitude of responses, possibly as immune responses were measured 6 weeks post second dose compared to 12 weeks post second dose.

摘要

背景

为了解使用不同剂量间隔的AZD1222疫苗时免疫反应的动力学,我们比较了两个具有不同剂量间隔的队列中的抗体和T细胞反应。

方法

在297名剂量间隔为12周的个体中评估了针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒的抗体,在第二剂接种后12周进行采样(队列1);在77名中位剂量间隔为21.4周的个体中(队列2)评估了抗体,在第二剂接种后6周进行采样。在一个亚组中评估了血管紧张素转换酶2(ACE2)受体阻断抗体(ACE2R-Abs)、针对病毒受体结合域(RBD)及关注变体(VOC)的抗体以及体外T细胞反应。

结果

所有个体(100%)均有SARS-CoV-2特异性总抗体,队列1中94.2%的个体和队列2中97.1%的个体有ACE2R阻断抗体。两个队列中不同年龄组的抗体滴度或阳性率均无差异。与队列1相比,队列2中的ACE2R阻断抗体(p<0.0001)和针对VOCs的RBD的抗体显著更高。在队列1中,不同年龄组41.2%至65.8%的个体通过血凝试验对原始病毒和VOCs的RBD呈阳性反应,而在队列2中这一比例为53.6%至90%。队列1中17/57(29.8%)的个体和队列2中17/29(58.6%)的个体的体外干扰素γ酶联免疫斑点试验(ELISpot)反应高于阳性阈值。第一剂接种后12周时的ACE2R阻断抗体和体外干扰素γ ELISpot反应分别与第二剂接种后12周时的水平显著相关(斯皮尔曼相关系数r=0.46,p=0.008)和(斯皮尔曼相关系数r=0.71,p<0.0001)。

结论

两种接种方案在接种疫苗后均产生了高水平的抗体和T细胞反应,尽管剂量间隔较长的个体反应程度更高,这可能是因为免疫反应是在第二剂接种后6周测量的,而队列1是在第二剂接种后12周测量的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8f0/8562553/7cee62300d2f/nihpp-2021.10.27.21265561v1-f0001.jpg

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