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科兴疫苗加强针可提高对 Delta 和 Omicron 变异株的中和抗体和 T 细胞应答。

A Booster Dose of CoronaVac Increases Neutralizing Antibodies and T Cells that Recognize Delta and Omicron Variants of Concern.

机构信息

Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.

Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

出版信息

mBio. 2022 Aug 30;13(4):e0142322. doi: 10.1128/mbio.01423-22. Epub 2022 Aug 10.

Abstract

CoronaVac is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization (WHO). Previous studies reported increased levels of neutralizing antibodies and specific T cells 2 and 4 weeks after two doses of CoronaVac; these levels were significantly reduced at 6 to 8 months after the two doses. Here, we report the effect of a booster dose of CoronaVac on the anti-SARS-CoV-2 immune response generated against the variants of concern (VOCs), Delta and Omicron, in adults participating in a phase III clinical trial in Chile. Volunteers immunized with two doses of CoronaVac in a 4-week interval received a booster dose of the same vaccine between 24 and 30 weeks after the second dose. Neutralization capacities and T cell activation against VOCs Delta and Omicron were assessed 4 weeks after the booster dose. We observed a significant increase in neutralizing antibodies 4 weeks after the booster dose. We also observed a rise in anti-SARS-CoV-2-specific CD4 T cells over time, and these cells reached a peak 4 weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2-specific T cells induced by the booster showed activity against VOCs Delta and Omicron. Our results show that a booster dose of CoronaVac increases adults' humoral and cellular anti-SARS-CoV-2 immune responses. In addition, immunity induced by a booster dose of CoronaVac is active against VOCs, suggesting adequate protection. CoronaVac is an inactivated vaccine against SARS-CoV-2 that has been approved by WHO for emergency use. Phase III clinical trials are in progress in several countries, including China, Brazil, Turkey, and Chile, and have shown safety and immunogenicity after two doses of the vaccine. This report characterizes immune responses induced by two doses of CoronaVac followed by a booster dose 5 months after the second dose in healthy Chilean adults. The data reported here show that a booster dose increased the immune responses against SARS-CoV-2, enhancing levels of neutralizing antibodies against the ancestral strain and VOCs. Similarly, anti-SARS-CoV-2 CD4 T cell responses were increased following the booster dose. In contrast, levels of gamma interferon secretion and T cell activation against the VOCs Delta and Omicron were not significantly different from those for the ancestral strain. Therefore, a third dose of CoronaVac in a homologous vaccination schedule improves its immunogenicity in healthy volunteers.

摘要

科兴新冠疫苗是一种由世界卫生组织(WHO)批准的 SARS-CoV-2 灭活疫苗。此前的研究报告称,接种两剂科兴新冠疫苗后 2 至 4 周,中和抗体和特异性 T 细胞水平会升高;在接种两剂疫苗 6 至 8 个月后,这些水平显著下降。在此,我们报告了在智利进行的 III 期临床试验中,成年人接种科兴新冠疫苗加强针后对关切变异株(VOCs)Delta 和奥密克戎产生的抗 SARS-CoV-2 免疫反应的效果。志愿者在 4 周间隔内接种两剂科兴新冠疫苗,在第二剂后 24 至 30 周接受相同疫苗的加强针。在加强针接种后 4 周评估对 VOCs Delta 和奥密克戎的中和能力和 T 细胞激活。我们观察到加强针接种后 4 周中和抗体显著增加。此外,随着时间的推移,抗 SARS-CoV-2 特异性 CD4 T 细胞也有所增加,这些细胞在加强针接种后 4 周达到峰值。此外,加强针诱导的中和抗体和 SARS-CoV-2 特异性 T 细胞对 VOCs Delta 和奥密克戎具有活性。我们的研究结果表明,科兴新冠疫苗加强针可提高成年人的体液和细胞抗 SARS-CoV-2 免疫反应。此外,科兴新冠疫苗加强针诱导的免疫对 VOCs 有效,表明有足够的保护作用。科兴新冠疫苗是一种针对 SARS-CoV-2 的灭活疫苗,已获得 WHO 的紧急使用授权。III 期临床试验正在包括中国、巴西、土耳其和智利在内的多个国家进行,结果显示两剂疫苗接种后的安全性和免疫原性。本报告描述了在健康智利成年人中接种两剂科兴新冠疫苗后再接种加强针 5 个月后诱导的免疫反应。这里报告的数据显示,加强针增加了对 SARS-CoV-2 的免疫反应,提高了对原始株和 VOCs 的中和抗体水平。同样,加强针接种后抗 SARS-CoV-2 的 CD4 T 细胞反应也增加了。相比之下,针对 VOCs Delta 和奥密克戎的γ干扰素分泌和 T 细胞激活水平与原始株相比没有显著差异。因此,在同源疫苗接种方案中接种第三剂科兴新冠疫苗可提高其在健康志愿者中的免疫原性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47b5/9426482/c0e76a2e4aae/mbio.01423-22-f001.jpg

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