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开发用于广泛的沙贝病毒免疫的二价RBD适应性新冠疫苗。

Development of bivalent RBD adapted COVID-19 vaccines for broad sarbecovirus immunity.

作者信息

Bruno Laura A, Pueblas Castro Celeste, Demaría Agostina, Prado Lineia, Fascetto Cassero Clara G, Saposnik Lucas M, Páez Córdoba Federico, Rodriguez Juan Manuel, Piccini Giulia, Antonelli Roberta, Lapini Giulia, Temperton Nigel, Del Priore Sabrina A, Hernando Insua Andres C, Kaufmann Ingrid G, Vega Julio C, Flo Juan M, Pasquevich Karina A, Coria Lorena M, Cassataro Juliana

机构信息

Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650), Buenos Aires, Argentina.

Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, San Martín (1650), Buenos Aires, Argentina.

出版信息

NPJ Vaccines. 2025 May 29;10(1):108. doi: 10.1038/s41541-025-01156-3.

Abstract

COVID-19 vaccine adaptation is critical to respond to continuously emerging SARS-CoV-2 variants with enhanced immune evasion. The ARVAC protein subunit vaccine, based on the receptor binding domain of the spike protein of SARS-CoV-2, has been adapted to XBB.1.5 and JN.1 variants, as monovalent and bivalent formulations. Preclinical studies in mice showed that ARVAC XBB.1.5 and JN.1 monovalent vaccines induced strong neutralizing antibodies against XBB and JN.1 lineages, though with limited efficacy against phylogenetically distant variants. By contrast, bivalent formulations combining Gamma antigen with either XBB.1.5 or JN.1 antigens demonstrated superior cross-neutralizing activity, covering variants from Ancestral to JN.1. Additionally, Gamma-containing bivalent vaccines elicited neutralizing antibodies against SARS-CoV-1, highlighting their potential for broad-spectrum immunity. Cellular immune studies confirmed robust CD4 T cell activation across all formulations. These findings support the continued adaptation of ARVAC to current circulant variants and propose ARVAC bivalent vaccines containing the Gamma antigen as a strategy for induction of pan-sarbecovirus immunity.

摘要

新冠病毒疫苗的适应性对于应对不断出现的具有更强免疫逃逸能力的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)变体至关重要。基于SARS-CoV-2刺突蛋白受体结合域的ARVAC蛋白亚单位疫苗已被适配为针对XBB.1.5和JN.1变体的单价和二价制剂。小鼠的临床前研究表明,ARVAC XBB.1.5和JN.1单价疫苗诱导产生了针对XBB和JN.1谱系的强效中和抗体,不过对亲缘关系较远的变体的效力有限。相比之下,将Gamma抗原与XBB.1.5或JN.1抗原结合的二价制剂表现出卓越的交叉中和活性,涵盖了从原始毒株到JN.1的各种变体。此外,含Gamma的二价疫苗引发了针对SARS-CoV-1的中和抗体,凸显了其产生广谱免疫的潜力。细胞免疫研究证实所有制剂都能强劲激活CD4 T细胞。这些发现支持继续使ARVAC适配当前流行的变体,并提出含有Gamma抗原的ARVAC二价疫苗作为诱导泛沙贝科病毒免疫的一种策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca8/12122808/f7eaaaa65b04/41541_2025_1156_Fig1_HTML.jpg

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