Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.
Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Front Immunol. 2021 Nov 9;12:747830. doi: 10.3389/fimmu.2021.747830. eCollection 2021.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible of the current pandemic ongoing all around the world. Since its discovery in 2019, several circulating variants have emerged and some of them are associated with increased infections and death rate. Despite the genetic differences among these variants, vaccines approved for human use have shown a good immunogenic and protective response against them. In Chile, over 70% of the vaccinated population is immunized with CoronaVac, an inactivated SARS-CoV-2 vaccine. The immune response elicited by this vaccine has been described against the first SARS-CoV-2 strain isolated from Wuhan, China and the D614G strain (lineage B). To date, four SARS-CoV-2 variants of concern described have circulated worldwide. Here, we describe the neutralizing capacities of antibodies secreted by volunteers in the Chilean population immunized with CoronaVac against variants of concern Alpha (B.1.1.7), Beta (B.1.351) Gamma (P.1) and Delta (B.617.2).
Volunteers enrolled in a phase 3 clinical trial were vaccinated with two doses of CoronaVac in 0-14 or 0-28 immunization schedules. Sera samples were used to evaluate the capacity of antibodies induced by the vaccine to block the binding between Receptor Binding Domain (RBD) from variants of concern and the human ACE2 receptor by an in-house ELISA. Further, conventional microneutralization assays were used to test neutralization of SARS-CoV-2 infection. Moreover, interferon-γ-secreting T cells against Spike from variants of concern were evaluated in PBMCs from vaccinated subjects using ELISPOT.
CoronaVac promotes the secretion of antibodies able to block the RBD of all the SARS-CoV-2 variants studied. Seropositivity rates of neutralizing antibodies in the population evaluated were over 97% for the lineage B strain, over 80% for Alpha and Gamma variants, over 75% for Delta variant and over 60% for the Beta variant. Geometric means titers of blocking antibodies were reduced when tested against SARS-CoV-2 variants as compared to ancestral strain. We also observed that antibodies from vaccinated subjects were able to neutralize the infection of variants D614G, Alpha, Gamma and Delta in a conventional microneutralization assay. Importantly, after SARS-CoV-2 infection, we observed that the blocking capacity of antibodies from vaccinated volunteers increased up to ten times for all the variants tested. We compared the number of interferon-γ-secreting T cells specific for SARS-CoV-2 Spike WT and variants of concern from vaccinated subjects and we did not detect significant differences.
Immunization with CoronaVac in either immunization schedule promotes the secretion of antibodies able to block SARS-CoV-2 variants of concern and partially neutralizes SARS-CoV-2 infection. In addition, it stimulates cellular responses against all variants of concern.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是导致目前全球大流行的病毒。自 2019 年发现以来，已经出现了几种流行变异株，其中一些与感染率和死亡率的增加有关。尽管这些变异株存在遗传差异，但已批准用于人类的疫苗对它们表现出良好的免疫原性和保护反应。在智利，超过 70%的接种人群接种了科兴疫苗（一种灭活的 SARS-CoV-2 疫苗）。该疫苗诱导的免疫应答已针对从中国武汉分离出的第一株 SARS-CoV-2 株和 D614G 株（谱系 B）进行了描述。迄今为止，已在全球范围内描述了四种令人关注的 SARS-CoV-2 变异株。在这里，我们描述了智利科兴疫苗接种人群中志愿者分泌的抗体对关注的变异株阿尔法（B.1.1.7）、贝塔（B.1.351）、伽马（P.1）和德尔塔（B.617.2）的中和能力。
参加 3 期临床试验的志愿者按照 0-14 天或 0-28 天的免疫接种方案接种两剂科兴疫苗。使用血清样本通过内部 ELISA 评估疫苗诱导的抗体阻断受体结合结构域（RBD）与人类 ACE2 受体之间结合的能力。此外，还使用传统的微量中和测定法测试 SARS-CoV-2 感染的中和作用。此外，使用 ELISPOT 评估接种人群中针对 Spike 的干扰素-γ分泌 T 细胞针对关注的变异株。
科兴疫苗促进了能够阻断所有研究的 SARS-CoV-2 变异株 RBD 的抗体的分泌。在评估的人群中，针对谱系 B 株的中和抗体血清阳性率超过 97%，针对阿尔法和伽马变异株的血清阳性率超过 80%，针对德尔塔变异株的血清阳性率超过 75%，针对贝塔变异株的血清阳性率超过 60%。与原始株相比，针对 SARS-CoV-2 变异株的阻断抗体的几何平均滴度降低。我们还观察到，接种受试者的抗体能够中和常规微量中和测定中 D614G、阿尔法、伽马和德尔塔变异株的感染。重要的是，在 SARS-CoV-2 感染后，我们观察到所有测试变异株的志愿者中和抗体的阻断能力增加了十倍以上。我们比较了来自接种受试者的针对 SARS-CoV-2 Spike WT 和关注的变异株的干扰素-γ分泌 T 细胞的数量，未发现显著差异。
无论免疫接种方案如何，接种科兴疫苗均可促进能够阻断关注的 SARS-CoV-2 变异株的抗体的分泌，并部分中和 SARS-CoV-2 感染。此外，它还刺激了针对所有关注变异株的细胞反应。
