Translational Health Science and Technology Institute, Faridabad, India.
Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology, New Delhi, India.
Lancet Infect Dis. 2022 Apr;22(4):473-482. doi: 10.1016/S1473-3099(21)00680-0. Epub 2021 Nov 25.
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.
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.
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.
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.
Department of Biotechnology India, Council of Scientific and Industrial Research India, and Fondation Botnar.
引起关注的 SARS-CoV-2 变体（VOCs）威胁着 COVID-19 疫苗的有效性。我们旨在评估 ChAdOx1 nCoV-19 疫苗的有效性，该疫苗主要针对 delta（B.1.617.2）变体，以及接种疫苗后的细胞免疫反应。
我们在印度法里达巴德的两个医学研究中心进行了一项病例对照研究。所有在 2021 年 4 月 1 日至 5 月 31 日期间 SARS-CoV-2 感染 RT-PCR 检测呈阳性的个体被视为病例，在与病例按 RT-PCR 检测周进行匹配后，RT-PCR 检测呈阴性的个体被视为对照。主要结局是 ChAdOx1 nCoV-19 疫苗完全接种对实验室确诊的 SARS-CoV-2 感染的有效性。次要结局是单剂疫苗对 SARS-CoV-2 感染的有效性，以及在感染个体中对中度至重度疾病的单剂和完全接种的有效性。此外，我们还在 ChAdOx1 nCoV-19 疫苗接种的健康（抗核衣壳抗体阴性）受者中测试了针对野生型 SARS-CoV-2 和 VOCs 的 Spike 蛋白的活病毒中和和 T 细胞免疫反应。
在 2379 例确诊的 SARS-CoV-2 感染病例中，85 例（3.6%）完全接种疫苗，而 1981 例对照中的 168 例（8.5%）（校正比值比[aOR]0.37[95%CI 0.28-0.48]），这表明疫苗对 SARS-CoV-2 感染的有效性为 63.1%（95%CI 51.5-72.1）。2451 例病例中有 157 例（6.4%）和 1994 例对照中有 181 例（9.1%）接受了 ChAdOx1 nCoV-19 疫苗的单剂接种（aOR 0.54[95%CI 0.42-0.68]），因此，单剂疫苗对 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 病例中有 1 例完全接种疫苗，而 2295 例轻度 COVID-19 病例中有 84 例（aOR 0.19[95%CI 0.01-0.90]），表明完全接种疫苗对中度至重度疾病的有效性为 81.5%（95%CI 9.9-99.0）。单剂疫苗对中度至重度疾病的有效性为 79.2%（95%CI 46.1-94.0）；87 例中度至重度 COVID-19 患者中有 4 例接受了单剂接种，而 2364 例轻度疾病患者中有 153 例（aOR 0.20[95%CI 0.06-0.54]）。在 49 名完全接种疫苗的健康个体中，针对 alpha（B.1.1.7；几何平均滴度 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]）和 delta（88.4[61.2-127.8]）变体的中和抗体反应均低于野生型 SARS-CoV-2（599.4[376.9-953.2]）。然而，针对 delta 变体和野生型 SARS-CoV-2 的 Spike 特异性 CD4 和 CD8 T 细胞反应仍然保持不变。
即使在 delta 变体高度传播的情况下，ChAdOx1 nCoV-19 疫苗仍对中度至重度 COVID-19 有效。针对 delta 变体的 Spike 特异性 T 细胞反应得以维持。这种细胞免疫保护可能弥补了体液免疫的减弱。
印度生物技术部、印度科学技术研究理事会和 Botnar 基金会。
