The Ad26.COV2.S vaccine^1,2,3 has demonstrated clinical efficacy against symptomatic COVID-19, including against the B.1.351 variant that is partially resistant to neutralizing antibodies¹. However, the immunogenicity of this vaccine in humans against SARS-CoV-2 variants of concern remains unclear. Here we report humoral and cellular immune responses from 20 Ad26.COV2.S vaccinated individuals from the COV1001 phase I–IIa clinical trial² against the original SARS-CoV-2 strain WA1/2020 as well as against the B.1.1.7, CAL.20C, P.1 and B.1.351 variants of concern. Ad26.COV2.S induced median pseudovirus neutralizing antibody titres that were 5.0-fold and 3.3-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020 on day 71 after vaccination. Median binding antibody titres were 2.9-fold and 2.7-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020. Antibody-dependent cellular phagocytosis, complement deposition and natural killer cell activation responses were largely preserved against the B.1.351 variant. CD8 and CD4 T cell responses, including central and effector memory responses, were comparable among the WA1/2020, B.1.1.7, B.1.351, P.1 and CAL.20C variants. These data show that neutralizing antibody responses induced by Ad26.COV2.S were reduced against the B.1.351 and P.1 variants, but functional non-neutralizing antibody responses and T cell responses were largely preserved against SARS-CoV-2 variants. These findings have implications for vaccine protection against SARS-CoV-2 variants of concern.

Ad26.COV2.S 疫苗^1、2、3已证明对有症状的 COVID-19 具有临床疗效，包括对部分抵抗中和抗体¹的 B.1.351 变体。然而，这种疫苗在人体中对 SARS-CoV-2 变体的免疫原性仍不清楚。在这里，我们报告了来自 COV1001 I-IIa 期临床试验的 20 名接种 Ad26.COV2.S 的个体的体液和细胞免疫反应²针对最初的 SARS-CoV-2 毒株 WA1/2020 以及针对 B.1.1.7、CAL.20C、P.1 和 B.1.351 的关注变体。在接种疫苗后第 71 天，与 WA1/2020 相比，Ad26.COV2.S 诱导的假病毒中和抗体滴度中值分别比 B.1.351 和 P.1 变体低 5.0 倍和 3.3 倍。与 WA1/2020 相比，针对 B.1.351 和 P.1 变体的中位结合抗体滴度分别低 2.9 倍和 2.7 倍。针对 B.1.351 变体，抗体依赖性细胞吞噬作用、补体沉积和自然杀伤细胞活化反应在很大程度上得以保留。CD8 和 CD4 T 细胞反应，包括中枢和效应记忆反应，在 WA1/2020、B.1.1.7、B.1.351、P.1 和 CAL.20C 变体中具有可比性。这些数据表明，Ad26.COV2.S 诱导的中和抗体对 B.1.351 和 P.1 变体的反应减少，但功能性非中和抗体反应和 T 细胞反应在很大程度上保留了对 SARS-CoV-2 变体的反应。这些发现对针对 SARS-CoV-2 变体的疫苗保护具有重要意义。