An intramuscular prime and mucosal boost vaccine regimen protects against lethal clade 2.3.4.4b H5N1 challenge in cynomolgus macaques

IF 14.6 1区医学 Q1 CELL BIOLOGY

Science Translational Medicine Pub Date : 2025-10-15 DOI:10.1126/scitranslmed.ady2282

Ninaad Lasrado, Liping Wang, Jinyan Liu, Annika Rössler, Jayeshbhai Chaudhari, Qixin Wang, Jonathon J. Stone, Francisco Armando Granados-Contreras, Jessica Wu, Dalia N. Cabrera-Barragan, Alejandra Waller-Pulido, Samuel J. Nangle, Krishna Shah, Reed Boduch, Siddhesh Warke, Anthony Cook, Christopher Kitajewski, Laurent Pessaint, Mark G. Lewis, Hanne Andersen, Amanda J. Martinot, Ryan P. McNamara, Dan H. Barouch

{"title":"An intramuscular prime and mucosal boost vaccine regimen protects against lethal clade 2.3.4.4b H5N1 challenge in cynomolgus macaques","authors":"Ninaad Lasrado, Liping Wang, Jinyan Liu, Annika Rössler, Jayeshbhai Chaudhari, Qixin Wang, Jonathon J. Stone, Francisco Armando Granados-Contreras, Jessica Wu, Dalia N. Cabrera-Barragan, Alejandra Waller-Pulido, Samuel J. Nangle, Krishna Shah, Reed Boduch, Siddhesh Warke, Anthony Cook, Christopher Kitajewski, Laurent Pessaint, Mark G. Lewis, Hanne Andersen, Amanda J. Martinot, Ryan P. McNamara, Dan H. Barouch","doi":"10.1126/scitranslmed.ady2282","DOIUrl":null,"url":null,"abstract":"<div >The H5N1 clade 2.3.4.4b avian influenza virus outbreak in poultry and dairy cattle is a potential pandemic threat for humans. A safe and effective H5N1 influenza vaccine will be needed if the virus acquires the capacity for efficient human-to-human transmission and may also be useful as a veterinary vaccine. In this study, we demonstrate robust vaccine protection in a lethal model of H5N1 clade 2.3.4.4b influenza infection in cynomolgus macaques. We vaccinated 24 cynomolgus macaques with mRNA or rhesus adenovirus serotype 52 (RhAd52) vaccines expressing the hemagglutinin (HA) from H5N1 clade 2.3.4.4b by the intramuscular or intratracheal route and challenged them with the H5N1 human isolate hu-TX37-H5N1. Of sham control animals, 83% (five of six) developed severe rapidly progressive consolidative pneumonia and were euthanized by days 5 to 7 after challenge. In contrast, 100% (17 of 17) of vaccinated macaques survived and controlled virus replication to undetectable titers in both the upper and lower respiratory tracts by days 4 to 14 after challenge. Mucosal boosting with the RhAd52 HA vaccine generated robust mucosal antibody and T cell responses and afforded 6.3 and 5.1 log<sub>10</sub> median viral load reductions in viral RNA with no detectable infectious virus titers compared with sham controls in bronchoalveolar lavage and nasal swabs, respectively. These data demonstrate that an adenovirus-vectored vaccine can protect against lethal H5N1 clade 2.3.4.4b challenge in nonhuman primates and further highlight the importance of vaccine-elicited mucosal immunity.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 820","pages":""},"PeriodicalIF":14.6000,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/scitranslmed.ady2282","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.science.org/doi/10.1126/scitranslmed.ady2282","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The H5N1 clade 2.3.4.4b avian influenza virus outbreak in poultry and dairy cattle is a potential pandemic threat for humans. A safe and effective H5N1 influenza vaccine will be needed if the virus acquires the capacity for efficient human-to-human transmission and may also be useful as a veterinary vaccine. In this study, we demonstrate robust vaccine protection in a lethal model of H5N1 clade 2.3.4.4b influenza infection in cynomolgus macaques. We vaccinated 24 cynomolgus macaques with mRNA or rhesus adenovirus serotype 52 (RhAd52) vaccines expressing the hemagglutinin (HA) from H5N1 clade 2.3.4.4b by the intramuscular or intratracheal route and challenged them with the H5N1 human isolate hu-TX37-H5N1. Of sham control animals, 83% (five of six) developed severe rapidly progressive consolidative pneumonia and were euthanized by days 5 to 7 after challenge. In contrast, 100% (17 of 17) of vaccinated macaques survived and controlled virus replication to undetectable titers in both the upper and lower respiratory tracts by days 4 to 14 after challenge. Mucosal boosting with the RhAd52 HA vaccine generated robust mucosal antibody and T cell responses and afforded 6.3 and 5.1 log₁₀ median viral load reductions in viral RNA with no detectable infectious virus titers compared with sham controls in bronchoalveolar lavage and nasal swabs, respectively. These data demonstrate that an adenovirus-vectored vaccine can protect against lethal H5N1 clade 2.3.4.4b challenge in nonhuman primates and further highlight the importance of vaccine-elicited mucosal immunity.

Abstract Image

查看原文本刊更多论文

在食蟹猕猴中，肌肉注射和粘膜强化疫苗方案可防止致命进化枝2.3.4.4b H5N1攻击

H5N1分支2.3.4.4b禽流感病毒在家禽和奶牛中的暴发是对人类的潜在大流行威胁。如果H5N1流感病毒获得了有效的人际传播能力，并且可能也可用作兽用疫苗，那么就需要一种安全有效的H5N1流感疫苗。在这项研究中，我们在食蟹猕猴的H5N1分支2.3.4.4b流感感染致死模型中证明了疫苗的强大保护作用。我们用表达H5N1分支2.3.4.4b血凝素（HA）的mRNA或RhAd52血清型病毒（RhAd52）疫苗通过肌肉或气管注射给24只食水猴，并用H5N1人分离株hu-TX37-H5N1攻毒。在假对照动物中，83%（6只中的5只）发展为严重的快速进展性巩固性肺炎，并在感染后5至7天被安乐死。相比之下，接种疫苗的猕猴100%（17只中的17只）存活，并在攻击后第4至14天将病毒复制控制在上呼吸道和下呼吸道的检测不到滴度。在支气管肺泡灌洗和鼻拭子中，与假对照组相比，使用RhAd52 HA疫苗增强粘膜产生了强大的粘膜抗体和T细胞反应，病毒RNA的中位数病毒载量分别降低了6.3和5.1 log 10，没有检测到感染性病毒滴度。这些数据表明，腺病毒载体疫苗可以保护非人灵长类动物免受致命的H5N1进化枝2.3.4.4b的攻击，并进一步强调了疫苗诱导的粘膜免疫的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

26.70

自引率

1.20%

发文量

309

审稿时长

1.7 months

期刊介绍： Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.