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康希诺-19/Spikogen® 疫苗基于重组刺突蛋白胞外域,与 Advax-CpG55.2 佐剂联合使用,可在仓鼠中提供针对 SARS-CoV-2 感染的单次剂量保护。

Covax-19/Spikogen® vaccine based on recombinant spike protein extracellular domain with Advax-CpG55.2 adjuvant provides single dose protection against SARS-CoV-2 infection in hamsters.

机构信息

Vaxine Pty Ltd, Bedford Park, Adelaide 5042, Australia; College of Medicine and Public Health, Flinders University, Adelaide 5042, Australia.

Vaxine Pty Ltd, Bedford Park, Adelaide 5042, Australia.

出版信息

Vaccine. 2022 May 20;40(23):3182-3192. doi: 10.1016/j.vaccine.2022.04.041. Epub 2022 Apr 18.


DOI:10.1016/j.vaccine.2022.04.041
PMID:35465982
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9013662/
Abstract

COVID-19 presents an ongoing global health crisis. Protein-based COVID-19 vaccines that are well-tolerated, safe, highly-protective and convenient to manufacture remain of major interest. We therefore sought to compare the immunogenicity and protective efficacy of a number of recombinant SARS-CoV-2 spike protein candidates expressed in insect cells. By comparison to a full length (FL) spike protein detergent-extracted nanoparticle antigen, the soluble secreted spike protein extracellular domain (ECD) generated higher protein yields per liter of culture and when formulated with either Alum-CpG55.2 or Advax-CpG55.2 combination adjuvants elicited robust antigen-specific humoral and cellular immunity in mice. In hamsters, the spike ECD when formulated with either adjuvant induced high serum neutralizing antibody titers even after a single dose. When challenged with the homologous SARS-CoV-2 virus, hamsters immunized with the adjuvanted spike ECD exhibited reduced viral load in day 1-3 oropharyngeal swabs and day 3 nasal turbinate tissue and had no recoverable infectious virus in day 3 lung tissue. The reduction in lung viral load correlated with less weight loss and lower lung pathology scores. The formulations of spike ECD with Alum-CpG55.2 or Advax-CpG55.2 were protective even after just a single dose, although the 2-dose regimen performed better overall and required only half the total amount of antigen. Pre-challenge serum neutralizing antibody levels showed a strong correlation with lung protection, with a weaker correlation seen with nasal or oropharyngeal protection. This suggests that serum neutralizing antibody levels may correlate more closely with systemic, rather than mucosal, protection. The spike protein ECD with Advax-CpG55.2 formulation (Covax-19® vaccine) was selected for human clinical development.

摘要

COVID-19 构成了持续的全球健康危机。具有良好耐受性、安全性、高度保护性且易于制造的基于蛋白质的 COVID-19 疫苗仍然是主要关注点。因此,我们试图比较在昆虫细胞中表达的几种重组 SARS-CoV-2 刺突蛋白候选物的免疫原性和保护效力。与全长(FL)刺突蛋白去污剂提取纳米颗粒抗原相比,可溶性分泌的刺突蛋白细胞外结构域(ECD)每升培养物产生的蛋白产量更高,并且当与 Alum-CpG55.2 或 Advax-CpG55.2 联合佐剂配方时,可在小鼠中引起强烈的抗原特异性体液和细胞免疫。在仓鼠中,当与任何一种佐剂配方时,刺突 ECD 诱导高血清中和抗体滴度,甚至在单次剂量后也是如此。用同源 SARS-CoV-2 病毒攻毒后,用佐剂免疫的仓鼠在第 1-3 天口咽拭子和第 3 天鼻甲骨组织中显示出降低的病毒载量,并且在第 3 天的肺组织中没有可恢复的感染性病毒。肺病毒载量的降低与体重减轻和肺部病理评分降低相关。用 Alum-CpG55.2 或 Advax-CpG55.2 配方的刺突 ECD 即使仅进行一剂也具有保护作用,尽管两剂方案总体效果更好,并且抗原总用量仅为一半。预攻毒血清中和抗体水平与肺部保护呈强相关性,而与鼻腔或口咽保护的相关性较弱。这表明血清中和抗体水平可能与全身保护而非粘膜保护更密切相关。用 Advax-CpG55.2 配方的刺突蛋白 ECD(Covax-19®疫苗)被选为人用临床开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8613/9013662/7d837c36eda1/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8613/9013662/04c454341644/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8613/9013662/0332a96ef53f/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8613/9013662/2cd980ceb5a7/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8613/9013662/7d837c36eda1/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8613/9013662/04c454341644/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8613/9013662/0332a96ef53f/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8613/9013662/2cd980ceb5a7/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8613/9013662/7d837c36eda1/gr4_lrg.jpg

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[3]
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[6]
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本文引用的文献

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