Immunogenicity and efficacy of heterologous ChAdOx1-BNT162b2 vaccination
Immunogenicity and efficacy of heterologous ChAdOx1-BNT162b2 vaccination
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DOI：
10.1038/s41586-021-04120-y
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发表时间：
2021-10-21
期刊：
影响因子：
64.8
通讯作者：
Trouillet-Assant, Sophie
中科院分区：
文献类型：
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作者：
Pozzetto, Bruno;Legros, Vincent;Trouillet-Assant, Sophie
在阿斯利康ChAdOx1-S-NCoV-19疫苗(1，2)出现严重不良反应后，欧洲卫生当局建议55岁以下接种一剂ChAdOx1-S-NCoV-19的患者接种第二剂辉瑞BNT162b2疫苗。然而，这种疫苗接种方案的有效性和免疫原性尚未得到正式测试。在对医护人员(n=13,121)的真实世界观察研究中，我们发现异源CHAdOx1-S-NCoV-19和BNT162b2组合比同源BNT162b2和BNT162b2组合对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的感染具有更好的保护作用。为了了解潜在的机制，我们对每种疫苗组合赋予的抗刺免疫进行了纵向调查。两种疫苗组合均可诱导较强的抗尖峰抗体反应，但无论SARS-CoV-2变异株如何，来自异种疫苗接种个体的血清均显示出更强的中和活性。这种增强的中和潜力与识别SARS-CoV-2受体结合域的开关和激活的记忆B细胞的频率增加相关。与BNT162b2疫苗相比，CHAdOx1-S-NCoV19疫苗免疫后的免疫应答较弱，而T细胞反应较强，说明两种疫苗联合使用具有互补性。因此，异种疫苗接种方案可能特别适合免疫功能低下的人。
Following severe adverse reactions to the AstraZeneca ChAdOxl-S-nCoV-19 vaccine(1,2), European health authorities recommended that patients under the age of 55 years who received one dose of ChAdOxl-S-nCoV-19 receive a second dose of the Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here we show that the heterologous ChAdOx1-S-nCoV-19 and BNT162b2 combination confers better protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the homologous BNT162b2 and BNT162b2 combination in a real-world observational study of healthcare workers (n = 13,121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody responses, but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential correlated with increased frequencies of switched and activated memory B cells that recognize the SARS-CoV-2 receptor binding domain. The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immunocompromised individuals.