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应对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的进化:基于六聚体原武汉株刺突蛋白或其更新的BA.2.75.2版本的AVX/COVID-12“Patria”疫苗对新出现的变异株的中和作用。

Addressing SARS-CoV-2 evolution: neutralization of emerging variants of concern by the AVX/COVID-12 'Patria' vaccine based on HexaPro-S ancestral Wuhan spike or its updated BA.2.75.2 version.

作者信息

Carballo-Uicab Gregorio, Mellado-Sánchez Gabriela, González-González Edith, Salinas-Trujano Juana, Mendoza-Salazar Ivette, López-Olvera Karina, Gómez-Castellano Keyla M, Salazar Ma Isabel, Torres-Flores Jesús M, Chagoya-Cortés Héctor Elías, Paz-De la Rosa Georgina, Mena Ignacio, Rojas-Martínez Oscar, Lara-Puente Jesús Horacio, Peralta-Sánchez Gustavo Javier, Sarfati-Mizrahi David, Torres-Flores Alejandro, Sun Weina, Krammer Florian, García-Sastre Adolfo, Palese Peter, López-Macías Constantino, Lozano-Dubernard Bernardo, Pérez-Tapia Sonia M, Almagro Juan C

机构信息

Unidad de Desarrollo e Investigación en Bioterapéuticos (UDIBI), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México City, México.

Laboratorio Nacional Para Servicios Especializados de Investigación, Desarrollo e Innovación (I+D+i) Para Farmoquímicos y Biotecnológicos, LANSEIDI-FarBiotec-CONACyT, México City, México.

出版信息

Front Immunol. 2025 May 19;16:1565934. doi: 10.3389/fimmu.2025.1565934. eCollection 2025.

Abstract

INTRODUCTION

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global health challenge, causing severe morbidity and mortality, particularly in vulnerable groups such as the elderly, immunocompromised individuals, and those with comorbidities. In low- and middle-income countries (LMICs), vaccine access is hindered by high costs and inequitable distribution. To tackle these issues, Mexico developed the AVX/COVID-12 (V-Wu) vaccine, a recombinant Newcastle disease virus (NDV)-based platform expressing a stabilized ancestral Wuhan spike protein (HexaPro-S). Locally manufactured after rigorous testing and regulatory approval, V-Wu aims to enhance self-sufficiency and equity in immunization.

METHODS

This study evaluates an updated vaccine version, AVX/COVID-12 (V-BA), designed to combat Omicron subvariants by expressing the HexaPro-S protein of BA.2.75.2. Both vaccines were administered intramuscularly in K18-hACE2 transgenic and BALB/c mouse models using a prime-boost regimen. Immunogenicity was analyzed by measuring antibodies against Omicron S proteins BA.2.75.2 and XBB.1.5, as well as neutralizing antibodies against Wuhan, BA.1, XBB.1.16, and JN.1 variants.

RESULTS

Both vaccines were safe, eliciting robust antibody responses against Omicron S proteins and neutralizing antibodies against multiple emerging SARS-CoV-2 variants of concern (VOCs). V-BA demonstrated superior protection against current Omicron variants, while V-Wu offered broader coverage, including the ancestral Wuhan strain and emerging variants like JN.1.

DISCUSSION

These findings underscore the adaptability of NDV-based platforms in addressing the evolving SARS-CoV-2 landscape and reaffirm the ongoing utility of the ancestral Patria vaccine. Together, they demonstrate the potential of these platforms to drive the development of next-generation vaccines tailored to emerging viral threats, contributing to global health equity.

摘要

引言

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)仍然是一项全球性的健康挑战,会导致严重的发病和死亡,尤其是在老年人、免疫功能低下者以及患有合并症的人群等弱势群体中。在低收入和中等收入国家(LMICs),高昂的成本和不公平的分配阻碍了疫苗的可及性。为解决这些问题,墨西哥研发了AVX/COVID-12(V-Wu)疫苗,这是一种基于重组新城疫病毒(NDV)的平台,表达一种稳定的原始武汉刺突蛋白(HexaPro-S)。经过严格测试和监管批准后在当地生产,V-Wu旨在提高免疫接种的自给自足能力和公平性。

方法

本研究评估了一种更新的疫苗版本AVX/COVID-12(V-BA),其通过表达BA.2.75.2的HexaPro-S蛋白来对抗奥密克戎亚变体。两种疫苗均使用初免-加强免疫方案在K18-hACE2转基因小鼠模型和BALB/c小鼠模型中进行肌肉注射。通过测量针对奥密克戎S蛋白BA.2.75.2和XBB.1.5的抗体,以及针对武汉、BA.1、XBB.1.16和JN.1变体的中和抗体来分析免疫原性。

结果

两种疫苗均安全,能引发针对奥密克戎S蛋白的强劲抗体反应以及针对多种新出现的严重急性呼吸综合征冠状病毒2关注变体(VOCs)的中和抗体。V-BA对当前的奥密克戎变体显示出更好的保护作用,而V-Wu提供了更广泛的覆盖范围,包括原始的武汉毒株和JN.1等新出现的变体。

讨论

这些发现强调了基于新城疫病毒的平台在应对不断演变的SARS-CoV-2形势方面的适应性,并重申了原始的祖国疫苗的持续效用。它们共同证明了这些平台推动开发针对新出现病毒威胁的下一代疫苗的潜力,有助于实现全球健康公平。

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