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在印度的一项混合匹配研究中,对两种和三种剂量的腺病毒载体疫苗 ChAdOx1 nCov-19 和全病毒灭活疫苗 BBV152 的免疫反应进行了特征描述。

Characterization of immune responses to two and three doses of the adenoviral vectored vaccine ChAdOx1 nCov-19 and the whole virion inactivated vaccine BBV152 in a mix-and-match study in India.

机构信息

The Wellcome Trust Research Laboratory, Christian Medical College, Vellore, India.

Department of Paediatrics, Christian Medical College, Vellore, India.

出版信息

Vaccine. 2023 Jul 25;41(33):4808-4822. doi: 10.1016/j.vaccine.2023.06.059. Epub 2023 Jun 23.

DOI:10.1016/j.vaccine.2023.06.059
PMID:37357073
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10289125/
Abstract

Infections with SARS-CoV-2 variants and declining immunity after primary vaccination, encouraged the use of booster doses. Some countries changed their immunization programmes to boost with vaccines different from the ones in their original schedule, based on results from immunogenicity and effectiveness studies. This study reports immunological analysis of samples collected in a phase 4 randomized trial, where participants who had previously received two primary doses of ChAdOx1 nCov-19 (ChAd) or inactivated BBV152 vaccine were randomized to receive either ChAd or BBV152 booster and further categorized as: Group 1 (two primary doses of ChAd - ChAd booster), Group 2 (two primary doses of ChAd - BBV152 booster), Group 3 (two primary doses of BBV152 - ChAd booster), and Group 4 (two primary doses of BBV152 - BBV152 booster). SARS-CoV-2 specific cellular and humoral responses at day 0 (pre-boost samples 12-36 weeks after the second primary dose), and at day 28 post booster, were measured in a subset of participants (ChAd recipients, n = 37 and BBV152 recipients, n = 36). Additionally, on day180 post-booster humoral responses were assessed for the entire cohort (N = 378). Primary vaccination with 2 doses of BBV152 generated higher memory-B cells (median% 0.41 vs 0.35) and cytokine producing CD8-Tcells (median% 0.09 vs 0.04) while lower anti-spike IgG levels (medianAU/ml: 12,433 vs 27,074) as compared to ChAd. Irrespective of the primary vaccine received, ChAd boosted individuals generated higher memory-B cell frequencies and anti-spike IgG levels as compared to BBV152 booster. The percentage ACE-2 inhibition against Omicron and its sub-variants was higher in Group 3 (median > 60 %) as compared to other groups (median < 25 %). At day180 post booster the hierarchy of the antibody amounts was Group 1 ∼ Group 2 ∼ Group 3 > Group 4. Sustained humoral and robust cellular immune response to SARS-CoV-2 can be obtained with ChAd booster irrespective of the primary vaccination regimen. The trial is registered with ISRTCN (CTRI/2021/08/035648).

摘要

在接种初始疫苗后,由于 SARS-CoV-2 变异株的感染和免疫下降,人们开始使用加强针。一些国家根据免疫原性和有效性研究的结果,改变了免疫计划,用不同的疫苗进行加强免疫。本研究报告了一项 4 期随机试验中采集的样本的免疫学分析,该试验中,先前接受过两剂腺病毒载体 ChAdOx1 nCov-19(ChAd)或灭活 BBV152 疫苗接种的参与者被随机分配接受 ChAd 或 BBV152 加强针,并进一步分为:第 1 组(两剂 ChAd- ChAd 加强针)、第 2 组(两剂 ChAd-BBV152 加强针)、第 3 组(两剂 BBV152-ChAd 加强针)和第 4 组(两剂 BBV152-BBV152 加强针)。在接种加强针后第 28 天,一小部分参与者(ChAd 组,n=37 人;BBV152 组,n=36 人)测量了 SARS-CoV-2 特异性细胞和体液反应。此外,在接种加强针后第 180 天,对整个队列(n=378 人)评估了体液反应。与 ChAd 相比,两剂 BBV152 接种可产生更高的记忆 B 细胞(中位数%:0.41 比 0.35)和产生细胞因子的 CD8-T 细胞(中位数%:0.09 比 0.04),但抗刺突 IgG 水平较低(中位数 AU/ml:12433 比 27074)。无论接受何种初始疫苗,与 BBV152 加强针相比,ChAd 加强针均可产生更高的记忆 B 细胞频率和抗刺突 IgG 水平。与其他组(中位数<25%)相比,第 3 组(中位数>60%)针对奥密克戎及其亚变体的 ACE-2 抑制率更高。在接种加强针后第 180 天,抗体数量的层次结构为第 1 组≈第 2 组≈第 3 组>第 4 组。无论初始接种方案如何,ChAd 加强针均可产生持续的体液和强大的细胞免疫反应来抵抗 SARS-CoV-2。该试验在 ISRTCN 注册(CTRI/2021/08/035648)。

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