A consensus HA DNA vaccine targeting clade 2.3.4.4 H5Nx influenza viruses provides broad cross-clade protection in mice and ferrets

IF 7.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy Pub Date : 2025-09-02 DOI:10.1016/j.biopha.2025.118485

Chang-Ung Kim , Won-Suk Choi , Pureum Lee , Ju Hwan Jeong , Yong Bok Seo , Young Woo Choi , Myung Ho Sohn , So-Young Choi , Ahn Young Jeong , Min-Suk Song , Doo-Jin Kim

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引用次数: 0

Abstract

Recurrent outbreaks of highly pathogenic avian influenza (HPAI) H5Nx viruses in birds pose a threat to human health due to their zoonotic potential. This underscores the urgent need for effective vaccines to mitigate the pandemic risk from evolving H5Nx viruses. We developed a DNA vaccine encoding a consensus hemagglutinin (HA) from clade 2.3.4.4 H5Nx viruses [pGX-27/HA (2.3.4.4)] and evaluated its immunogenicity and protective efficacy in mice and ferrets. Vaccination elicited strong neutralizing antibody and T cell responses, protecting mice against lethal challenge with homologous viruses. Unlike formalin-inactivated vaccines, the DNA vaccine conferred CD8⁺ T cell–mediated cross-protection against divergent clades 2.2.1.2 and 2.3.2.1. In ferrets, the vaccine induced neutralizing antibodies and conferred protective immunity, indicating translational potential. These results suggest that the HA (2.3.4.4) DNA vaccine provides broad immunity against multiple H5Nx clades and offers insights for developing next-generation vaccines against potential zoonotic influenza threats.

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针对进化支2.3.4.4 H5Nx流感病毒的HA DNA疫苗在小鼠和雪貂中提供广泛的跨进化保护

高致病性禽流感（HPAI） H5Nx病毒在禽类中反复暴发，由于其人畜共患的潜力，对人类健康构成威胁。这突出表明迫切需要有效的疫苗，以减轻不断演变的H5Nx病毒造成的大流行风险。我们从2.3.4.4支H5Nx病毒[pGX-27/HA(2.3.4.4)]中开发了一种编码共识血凝素（HA）的DNA疫苗，并评估了其在小鼠和雪貂中的免疫原性和保护效果。疫苗接种引起强烈的中和抗体和T细胞反应，保护小鼠免受同源病毒的致命攻击。与福尔马林灭活疫苗不同，DNA疫苗提供CD8 + T细胞介导的交叉保护，以对抗不同的进化枝2.2.1.2和2.3.2.1。在雪貂中，疫苗诱导了中和抗体并赋予保护性免疫，表明了转化潜力。这些结果表明，HA (2.3.4.4) DNA疫苗对多种H5Nx分支具有广泛的免疫力，并为开发针对潜在人畜共患流感威胁的下一代疫苗提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomedicine & Pharmacotherapy 医学-药学

CiteScore

11.90

自引率

2.70%

发文量

1621

审稿时长

48 days

期刊介绍： Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.