A Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection.

A Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection.
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DOI:
10.1038/s41467-024-45180-8
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发表时间:
2024-02-02
影响因子:
16.6
通讯作者:
Cassataro, Juliana
Cassataro, Juliana
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Coria, Lorena M.;Rodriguez, Juan Manuel;Demaria, Agostina;Bruno, Laura A.;Medrano, Mayra Rios;Castro, Celeste Pueblas;Castro, Eliana F.;Del Priore, Sabrina A.;Insua, Andres C. Hernando;Kaufmann, Ingrid G.;Saposnik, Lucas M.;Stone, William B.;Prado, Lineia;Notaro, Ulises S.;Amweg, Ayelen N.;Diaz, Pablo U.;Avaro, Martin;Ortega, Hugo;Ceballos, Ana;Krum, Valeria;Zurvarra, Francisco M.;Sidabra, Johanna E.;Drehe, Ignacio;Baque, Jonathan A.;Li Causi, Mariana;De Nichilo, Analia V.;Payes, Cristian J.;Southard, Teresa;Vega, Julio C.;Auguste, Albert J.;Alvarez, Diego E.;Flo, Juan M.;Pasquevich, Karina A.;Cassataro, Juliana

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在SARS-CoV-2变异体不断出现的背景下,预防COVID-19严重后果的一项策略是开发安全有效的广谱疫苗。在这里,我们提出了一种RBD疫苗的临床前研究,该疫苗来源于以明矾为佐剂的γ SARS-CoV-2变体。就诱导更广泛的中和抗体而言,γ适应性RBD疫苗比祖先RBD疫苗更具免疫原性。γ RBD呈现更多免疫原性B细胞限制性表位,并诱导比祖先RBD版本更高比例的特异性B细胞和浆母细胞。γ适应疫苗诱导抗原特异性T细胞免疫应答,并在小鼠中赋予针对Ancestic和Omicron BA.5 SARS-CoV-2攻击的保护。此外,在先前用不同SARS-CoV-2疫苗平台致敏的小鼠中,γ RBD疫苗比同源加强疫苗接种诱导更高和更广泛的中和抗体活性。我们的研究表明,佐剂γ RBD疫苗是高度免疫原性和广谱疫苗候选者。在这里,作者表明,基于γ的亚单位疫苗诱导针对SARS-CoV-2变体(包括Omicron)的广泛中和抗体,诱导细胞免疫应答,并保护小鼠免受Omicron BA.5 SARS-CoV-2感染。
In the context of continuous emergence of SARS-CoV-2 variants of concern (VOCs), one strategy to prevent the severe outcomes of COVID-19 is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies of a RBD vaccine derived from the Gamma SARS-CoV-2 variant adjuvanted with Alum. The Gamma-adapted RBD vaccine is more immunogenic than the Ancestral RBD vaccine in terms of inducing broader neutralizing antibodies. The Gamma RBD presents more immunogenic B-cell restricted epitopes and induces a higher proportion of specific-B cells and plasmablasts than the Ancestral RBD version. The Gamma-adapted vaccine induces antigen specific T cell immune responses and confers protection against Ancestral and Omicron BA.5 SARS-CoV-2 challenge in mice. Moreover, the Gamma RBD vaccine induces higher and broader neutralizing antibody activity than homologous booster vaccination in mice previously primed with different SARS-CoV-2 vaccine platforms. Our study indicates that the adjuvanted Gamma RBD vaccine is highly immunogenic and a broad-spectrum vaccine candidate. Here the authors show that a Gamma-based subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants including Omicron, induces cellular immune responses, and protects mice from infection with Omicron BA.5 SARS-CoV-2.
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