A Miniature Pig Model for the Study of Host-Immune Responses Against Influenza A Virus

用于研究甲型流感病毒宿主免疫反应的小型猪模型

• 批准号: 10216937
• 负责人: Juergen A Richt
• 金额: $ 19.88万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10216937
• 关键词: Animal Model; Animals; B-Lymphocytes; Cessation of life; Clinical; Clinical Research; Complement; Containment; Development; Development Plans; Disease; Dose; Economics; Enzyme-Linked Immunosorbent Assay; Epidemic; Exposure to; Family suidae; Haplotypes; Healthcare Systems; Homo; Hospitalization; Human; Immune; Immune response; Immunity; Immunologic Monitoring; Immunologics; Inactivated Vaccines; Inbreeding; Infection; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A virus; Influenza vaccination; Knowledge; Longitudinal Studies; Lung diseases; Membrane Proteins; Modeling; Monitor; Morbidity - disease rate; Mus; National Institute of Allergy and Infectious Disease; Outcome; Pathology; Population; Public Health; Publishing; Respiratory Tract Infections; Seasons; Strategic Planning; Stress; Study models; Symptoms; T-Lymphocyte; Testing; Time; Upper Respiratory Infections; Vaccinated; Vaccination; Vaccines; Viral Proteins; Virulent; Virus; Virus Diseases; Virus Replication; Weight Gain; Work; age group; cost; economic cost; experimental study; feasibility testing; influenza infection; influenza virus strain; influenza virus vaccine; influenzavirus; mouse model; neutralizing antibody; novel; pandemic disease; porcine model; tool; universal influenza vaccine; universal vaccine; vaccination strategy; vaccine development; vaccine evaluation; vaccine response; vaccine trial

Influenza viruses cause infections of the respiratory tract in both humans and pigs. Antigenic drift allows viruses to escape pre-existing immunity present in the human population and cause annual epidemics that results in significant morbidity, economic loss, and an estimated 250,000 deaths per year worldwide. Antigenic shift allows the creation of new influenza viruses with novel surface proteins that are antigenically unrelated to surface proteins of viruses that circulated in previous seasons. Currently licensed vaccines aim at the induction of neutralizing antibodies and their efficacy depends on accurate prediction of the influenza strains that will circulate in the next season. Protection provided by current vaccines is limited in time since antigenic drift and shift allow influenza viruses to escape vaccine-induced neutralizing antibodies, and there is a critical need for broad and long-lasting vaccines that provide protection against influenza viruses of different subtypes in all age groups. The development of such universal influenza vaccines is of public health importance and the outlines of a strategic plan have been published recently by the National Institute of Allergy and Infectious Diseases. One of the action items is to develop animal models that recapitulate human immunity to influenza virus infection and vaccination. In this project proposal, we plan to further develop the miniature pig model for the study of host-immune responses to influenza A virus infection and vaccination. We choose to work with miniature pigs because they are natural influenza hosts, easier to handle and to obtain seronegative animals than with conventional pigs and because haplotyped inbred animals are available. In the first part of the project we will focus on the establishment of an influenza A infection and re-infection model with miniature pigs to complement clinical studies previously performed in humans and the conventional pig influenza model. Immune responses induced by the first influenza infection will be monitored and correlated with protection against re-infection with a heterosubtypic influenza virus. In the second part of the project we will focus on the establishment of an influenza A vaccine model with miniature pigs to evaluate universal vaccine approaches and compare them to a conventional influenza vaccine. We will also investigate if the miniature pig influenza model is suitable for the study of vaccine-associated enhancement of disease, as is described for conventional pigs. This project will allow to define correlates of protective immunity against influenza A viruses of different subtypes and is crucial to close knowledge gaps in the current models for universal influenza vaccine studies.

流感病毒会引起人类和猪的呼吸道感染。抗原漂移使病毒能够逃脱人类中预先存在的免疫力，并引起年度流行病，导致全世界每年出现严重的发病率、经济损失和估计 250,000 人死亡。抗原转变允许产生具有新表面蛋白的新流感病毒，这些新表面蛋白与前一季节传播的病毒的表面蛋白在抗原上无关。目前获得许可的疫苗旨在诱导中和抗体，其功效取决于对下一季节将流行的流感毒株的准确预测。当前疫苗提供的保护在时间上是有限的，因为抗原漂移和转移使流感病毒逃脱疫苗诱导的中和抗体，因此迫切需要广泛且持久的疫苗，以针对所有年龄段的不同亚型流感病毒提供保护组。开发这种通用流感疫苗对公共卫生具有重要意义，国家过敏和传染病研究所最近发​​布了战略计划纲要。其中一项行动是开发动物模型，以重现人类对流感病毒感染和疫苗接种的免疫力。在本项目建议中，我们计划进一步开发小型猪模型，用于研究甲型流感病毒感染和疫苗接种的宿主免疫反应。我们选择与小型猪合作，因为它们是天然流感宿主，比传统猪更容易处理和获得血清阴性动物，而且因为可以获得单倍型近交动物。在该项目的第一部分，我们将重点关注建立小型猪甲型流感感染和再感染模型，以补充之前在人类和传统猪流感模型中进行的临床研究。将监测首次流感感染引起的免疫反应，并将其与防止异亚型流感病毒再次感染的保护联系起来。在该项目的第二部分，我们将重点建立小型猪甲型流感疫苗模型，以评估通用疫苗方法并将其与传统流感疫苗进行比较。我们还将研究小型猪流感模型是否适合研究疫苗相关的疾病增强，如对传统猪的描述。该项目将允许定义针对不同亚型甲型流感病毒的保护性免疫的相关性，并且对于缩小当前通用流感疫苗研究模型中的知识差距至关重要。

项目成果

Lipid nanoparticle composition for adjuvant formulation modulates disease after influenza virus infection in QIV vaccinated mice.

用于佐剂制剂的脂质纳米颗粒组合物在QIV疫苗接种的小鼠中调节流感病毒感染后的疾病。

• 发表时间: 2024-01-15
• 作者: Jangra, Sonia;Lamoot, Alexander;Singh, Gagandeep;Laghlali, Gabriel;Chen, Yong;Yz, Tingting;García;De Geest, Bruno G;Schotsaert, Michael
• 通讯作者: Schotsaert, Michael