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基于严重急性呼吸综合征冠状病毒2(SARS-CoV-2)及其变体的非糖基化受体结合域(RBD)抗原的多价蛋白亚单位疫苗的免疫原性

Immunogenicity of a multivalent protein subunit vaccine based on non-glycosylated RBD antigens of SARS-cov-2 and its variants.

作者信息

Calderón-Pérez Berenice, Núñez-Muñoz Leandro Alberto, Trejo-Ayala Lady Laura, Rosales-García Víctor Hugo, Chávez-Álvarez Benjamín Emmanuel, Vargas-Hernández Brenda Yazmín, Ramírez-Pool José Abrahán, Ruiz-Medrano Roberto, Xoconostle-Cázares Beatriz

机构信息

Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Departamento de Biotecnología y Bioingeniería, Av. Instituto Politécnico Nacional 2508, Mexico City, 07360, Mexico.

CINVESTAV, Laboratorios Nacionales de Servicios Experimentales (LANSE), Mexico.

出版信息

Virology. 2025 Feb;603:110380. doi: 10.1016/j.virol.2024.110380. Epub 2024 Dec 24.

Abstract

COVID-19 infections continue due to accessibility barriers to vaccines and the emergence of SARS-CoV-2 variants. An effective, safe, accessible, and broad-spectrum vaccine is still needed to control the disease. We developed a multivalent protein subunit vaccine comprising antigens designed from a non-N-glycosylated region of the receptor-binding domain of the spike protein of SARS-CoV-2. We combined a previously developed antigen based on the Wuhan original viral strain, and a site-mutated antigen based on several variants including Alpha, Beta, Gamma, Eta, Iota, Theta, Zeta, Mu and Omicron. The recombinant antigens were expressed in a prokaryotic system and the immunogenicity of the multivalent vaccine was tested in a mouse model. The evaluation of the subunit vaccine candidate, incorporating different variant-based multivalent recombinant antigens from non-glycosylated regions of the RBD, demonstrated a favorable safety profile, significant immunogenicity, and potent neutralizing activity, collectively supporting its potential efficacy and safety for further development.

摘要

由于疫苗可及性障碍以及严重急性呼吸综合征冠状病毒2(SARS-CoV-2)变体的出现,新型冠状病毒肺炎(COVID-19)感染仍在持续。仍需要一种有效、安全、可及且具有广谱性的疫苗来控制该疾病。我们研发了一种多价蛋白亚单位疫苗,其包含从SARS-CoV-2刺突蛋白受体结合域的非N糖基化区域设计的抗原。我们将先前基于武汉原始病毒株开发的抗原,与基于包括阿尔法、贝塔、伽马、伊塔、约塔、西塔、泽塔、缪和奥密克戎等几种变体的位点突变抗原相结合。重组抗原在原核系统中表达,并在小鼠模型中测试了多价疫苗的免疫原性。对候选亚单位疫苗的评估纳入了来自RBD非糖基化区域的不同基于变体的多价重组抗原,结果显示出良好的安全性、显著的免疫原性和强大的中和活性,共同支持其进一步开发的潜在有效性和安全性。

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