Leonard Rebecca A, Spurrier M Ariel, Skavicus Samantha, Luo Zhaochen, Heaton Brook E, Spreng Rachel L, Hong Jiaqi, Yuan Fan, Heaton Nicholas S
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
J Virol. 2025 Jul 16:e0079525. doi: 10.1128/jvi.00795-25.
Effective vaccines are an important public health tool which may be needed to combat the emerging, highly pathogenic H5N1 avian influenza viruses currently circulating in cattle and poultry in the United States. While nucleic acid-based vaccines such as mRNA-lipid nanoparticles (LNPs) have several potential advantages during a viral epidemic compared to traditional seasonal influenza vaccines, their utility and efficacy against H5N1 viruses remain incompletely defined. Here, we developed novel DNA- and mRNA-LNP-based vaccines encoding both hemagglutinin (HA) and neuraminidase (NA) proteins from the human-isolated highly pathogenic avian influenza H5N1 strain, A/Texas/37/2024, in a single open reading frame. This dual-antigen expression approach elicited strong protective immune responses targeting both the HA and NA proteins and provided complete protection against lethal viral challenges in a murine model. The pre-clinical data described in this work suggest that these multi-valent, adaptable, and scalable vaccine approaches may represent practical and rapid solutions to mediate robust protection from emerging zoonotic influenza virus threats.
Vaccines capable of protecting from infection with the H5N1 influenza viruses actively circulating in dairy cattle could be deployed to protect livestock and potentially also be used to protect human health. Here, we describe the development of protective DNA and mRNA-lipid nanoparticle vaccines targeting hemagglutinin and neuraminidase proteins from the highly pathogenic avian influenza (HPAI) H5N1 A/Texas/37/2024 virus and show that they are both protective against severe morbidity and mortality in a mouse model. Thus, the vaccines described in this work represent effective approaches to limit the current circulation of H5N1 viruses in animals and may represent practical solutions for human vaccination in the event of sustained human transmission of HPAI H5N1 viruses.
有效的疫苗是一种重要的公共卫生工具，可能需要用于对抗目前在美国牛和家禽中传播的新型高致病性H5N1禽流感病毒。与传统的季节性流感疫苗相比，基于核酸的疫苗，如mRNA-脂质纳米颗粒（LNP），在病毒流行期间具有几个潜在优势，但其对H5N1病毒的效用和效力仍未完全明确。在此，我们开发了新型的基于DNA和mRNA-LNP的疫苗，在单个开放阅读框中编码来自人分离的高致病性禽流感H5N1毒株A/德克萨斯/37/2024的血凝素（HA）和神经氨酸酶（NA）蛋白。这种双抗原表达方法引发了针对HA和NA蛋白的强烈保护性免疫反应，并在小鼠模型中提供了针对致死性病毒攻击的完全保护。这项工作中描述的临床前数据表明，这些多价、适应性强且可扩展的疫苗方法可能代表了切实可行且快速的解决方案，以介导对新出现的人畜共患流感病毒威胁的强大保护。
能够预防在奶牛中活跃传播的H5N1流感病毒感染的疫苗，可用于保护家畜，也有可能用于保护人类健康。在此，我们描述了针对高致病性禽流感（HPAI）H5N1 A/德克萨斯/37/2024病毒的血凝素和神经氨酸酶蛋白开发保护性DNA和mRNA-脂质纳米颗粒疫苗，并表明它们在小鼠模型中均能预防严重发病和死亡。因此，这项工作中描述的疫苗代表了限制H5N1病毒目前在动物中传播的有效方法，并且在HPAI H5N1病毒持续人传人的情况下，可能代表了人类疫苗接种的切实可行的解决方案。
