Background

SARS-CoV-2 variants of concern (VOCs) have threatened COVID-19 vaccine effectiveness. We aimed to assess the effectiveness of the ChAdOx1 nCoV-19 vaccine, predominantly against the delta (B.1.617.2) variant, in addition to the cellular immune response to vaccination.

Methods

We did a test-negative, case-control study at two medical research centres in Faridabad, India. All individuals who had a positive RT-PCR test for SARS-CoV-2 infection between April 1, 2021, and May 31, 2021, were included as cases and individuals who had a negative RT-PCR test were included as controls after matching with cases on calendar week of RT-PCR test. The primary outcome was effectiveness of complete vaccination with the ChAdOx1 nCoV-19 vaccine against laboratory-confirmed SARS-CoV-2 infection. The secondary outcomes were effectiveness of a single dose against SARS-CoV-2 infection and effectiveness of a single dose and complete vaccination against moderate-to-severe disease among infected individuals. Additionally, we tested in-vitro live-virus neutralisation and T-cell immune responses to the spike protein of the wild-type SARS-CoV-2 and VOCs among healthy (anti-nucleocapsid antibody negative) recipients of the ChAdOx1 nCoV-19 vaccine.

Findings

Of 2379 cases of confirmed SARS-CoV-2 infection, 85 (3·6%) were fully vaccinated compared with 168 (8·5%) of 1981 controls (adjusted OR [aOR] 0·37 [95% CI 0·28–0·48]), giving a vaccine effectiveness against SARS-CoV-2 infection of 63·1% (95% CI 51·5–72·1). 157 (6·4%) of 2451 of cases and 181 (9·1%) of 1994) controls had received a single dose of the ChAdOx1 nCoV-19 vaccine (aOR 0·54 [95% CI 0·42–0·68]), thus vaccine effectiveness of a single dose against SARS-CoV-2 infection was 46·2% (95% CI 31·6–57·7). One of 84 cases with moderate-to-severe COVID-19 was fully vaccinated compared with 84 of 2295 cases with mild COVID-19 (aOR 0·19 [95% CI 0·01–0·90]), giving a vaccine effectiveness of complete vaccination against moderate-to-severe disease of 81·5% (95% CI 9·9–99·0). The effectiveness of a single dose against moderate-to-severe disease was 79·2% (95% CI 46·1–94·0); four of 87 individuals with moderate-to-severe COVID-19 had received a single dose compared with 153 of 2364 participants with mild disease (aOR 0·20 [95% CI 0·06–0·54]). Among 49 healthy, fully vaccinated individuals, neutralising antibody responses were lower against the alpha (B.1.1.7; geometric mean titre 244·7 [95% CI 151·8–394·4]), beta (B.1.351; 97·6 [61·2–155·8]), kappa (B.1.617.1; 112·8 [72·7–175·0]), and delta (88·4 [61·2–127·8]) variants than against wild-type SARS-CoV-2 (599·4 [376·9–953·2]). However, the antigen-specific CD4 and CD8 T-cell responses were conserved against both the delta variant and wild-type SARS-CoV-2.

Interpretation

The ChAdOx1 nCoV-19 vaccine remained effective against moderate-to-severe COVID-19, even during a surge that was dominated by the highly transmissible delta variant of SARS-CoV-2. Spike-specific T-cell responses were maintained against the delta variant. Such cellular immune protection might compensate for waning humoral immunity.

Funding

Department of Biotechnology India, Council of Scientific and Industrial Research India, and Fondation Botnar.

中文翻译：

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印度 Delta (B.1.617.2) 变异激增期间 ChAdOx1 nCoV-19 疫苗对抗 SARS-CoV-2 感染的有效性：测试阴性、病例对照研究和疫苗接种后免疫反应的机制研究

 背景

SARS-CoV-2 相关变体 (VOC) 已威胁到 COVID-19 疫苗的有效性。我们的目的是评估 ChAdOx1 nCoV-19 疫苗的有效性，主要针对 delta (B.1.617.2) 变体，以及对疫苗接种的细胞免疫反应。

 方法

我们在印度法里达巴德的两个医学研究中心进行了一项测试阴性的病例对照研究。 2021 年 4 月 1 日至 2021 年 5 月 31 日期间，所有 SARS-CoV-2 感染 RT-PCR 检测呈阳性的个体均被纳入为病例，RT-PCR 检测呈阴性的个体在与RT-PCR 检测日历周内的病例。主要结果是完全接种 ChAdOx1 nCoV-19 疫苗对实验室确诊的 SARS-CoV-2 感染的有效性。次要结果是单剂疫苗对 SARS-CoV-2 感染的有效性以及单剂疫苗和完整疫苗接种对感染者中重度疾病的有效性。此外，我们还在 ChAdOx1 nCoV-19 疫苗的健康接受者（抗核衣壳抗体阴性）中测试了对野生型 SARS-CoV-2 刺突蛋白和 VOC 的体外活病毒中和和 T 细胞免疫反应。

 发现

在 2379 例确诊的 SARS-CoV-2 感染病例中，85 例 (3·6%) 完全接种了疫苗，而 1981 年对照组中有 168 例 (8·5%) 接种了疫苗（调整后 OR [aOR] 0·37 [95% CI 0·28 –0·48]），疫苗针对 SARS-CoV-2 感染的有效性为 63·1%（95% CI 51·5–72·1）。 2451 例病例中的 157 例 (6·4%) 和 1994 年的 181 例对照 (9·1%) 接受了单剂 ChAdOx1 nCoV-19 疫苗（aOR 0·54 [95% CI 0·42–0· 68]），因此单剂量疫苗对抗 SARS-CoV-2 感染的有效性为 46·2%（95% CI 31·6–57·7）。 84 例中度至重度 COVID-19 病例中的 1 例已完全接种疫苗，而 2295 例轻度 COVID-19 病例中的 84 例已完全接种疫苗 (aOR 0·19 [95% CI 0·01–0·90])，显示疫苗有效性针对中重度疾病的完全疫苗接种率为 81·5%（95% CI 9·9–99·0）。单剂量治疗中重度疾病的有效性为 79·2% (95% CI 46·1–94·0)； 87 名中度至重度 COVID-19 患者中有 4 人接受过单次剂量治疗，而 2364 名患有轻度疾病的参与者中有 153 人接受过单剂注射（aOR 0·20 [95% CI 0·06–0·54]）。在 49 名健康、完全接种疫苗的个体中，针对 α（B.1.1.7；几何平均滴度 244·7 [95% CI 151·8–394·4]）、β（B.1.351；97）的中和抗体反应较低·6 [61·2–155·8])、kappa (B.1.617.1; 112·8 [72·7–175·0]) 和 delta (88·4 [61·2–127·8]) ) 变异体比针对野生型 SARS-CoV-2 (599·4 [376·9–953·2]) 的变异体。然而，针对 delta 变体和野生型 SARS-CoV-2 的抗原特异性 CD4 和 CD8 T 细胞反应都是保守的。

 解释

即使在以高度传染性的 SARS-CoV-2 δ 变体为主的病例激增期间，ChAdOx1 nCoV-19 疫苗仍然对中度至重度 COVID-19 有效。针对 delta 变体，维持了尖峰特异性 T 细胞反应。这种细胞免疫保护可能会弥补体液免疫的减弱。

 资金

印度生物技术部、印度科学与工业研究委员会和博特纳基金会。