Syrian hamsters as an animal model for influenza virus research

叙利亚仓鼠作为流感病毒研究的动物模型

• 批准号: 10686861
• 负责人: YOSHIHIRO KAWAOKA
• 金额: $ 75.18万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-02 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10686861
• 关键词: Address; Adult; Aerosols; Animal Model; Animals; B-Lymphocytes; Back; Child; Childhood; Clinical; Clinical Trials; Cohort Studies; Complex; Data; Development; Development Plans; Dose; Educational workshop; Exposure to; Hamsters; Human; Immune; Immune response; Immunity; Inactivated Vaccines; Infection; Influenza A Virus, H3N2 Subtype; Influenza A virus; Influenza vaccination; Mesocricetus auratus; Modeling; Mus; National Institute of Allergy and Infectious Disease; Pediatric cohort; Persons; Phase; Predictive Value; Predictive Value of Tests; Recording of previous events; Research; Research Project Grants; Research Proposals; Respiratory System; Route; Sampling; Shapes; Strategic Planning; Testing; Vaccinated; Vaccination; Vaccines; Virus; Virus Receptors; Virus Replication; experimental study; exposure route; human model; immunological status; imprint; improved; influenza infection; influenza virus vaccine; influenzavirus; novel; respiratory; response; time interval; universal influenza vaccine; vaccine candidate; vaccine trial; viral transmission

PROJECT SUMMARY To facilitate NIAID’s strategic plan for the development of a universal influenza vaccine, PAR-19-248 solicits “Research Projects to Improve the Predictive Value of Animal Models in Recapitulating Human Immunity to Influenza Infection and Vaccination”. Here, we address some of the major research needs identified in PAR-19- 248 by continuing our development of golden Syrian hamsters (hereafter referred to as hamsters) as an animal model for influenza virus research. This is based on our previous findings that the composition of influenza virus receptors in the respiratory tract of hamsters is similar to that in the respiratory tract of humans, and that human influenza A viruses replicate in the respiratory tract of hamsters, including recent human H3N2 influenza viruses, which do not replicate efficiently in mice. In Specific Aim 1, we plan to establish an influenza virus aerosol exposure platform for hamsters. Currently, most influenza virus infection studies entail intranasal virus inoculation, which is not the natural route of infection (i.e., aerosol exposure). By establishing an aerosol exposure platform for hamsters, we are addressing a key topic of PAR-19-248. In Specific Aim 2, we will assess the predictive value of hamsters in simulating the impact of the first exposure to influenza viruses on subsequent exposures (imprinting). With few exceptions, influenza virus infection and vaccination studies have been conducted in naïve animals, thus not reflecting the immune status of most humans who have been exposed to multiple influenza viruses through infections and/or vaccinations. Here, we will sequentially infect hamsters (via intranasal infection or aerosol exposure) with the same human influenza viruses that caused the first and second infections in a child (based on clinical samples that we have obtained from a pediatric cohort study). Hamster and human sera will then be compared for B cell responses to the first and second infections. In Specific Aim 3, we will assess the predictive value of hamsters in simulating human immune responses to multiple infections, vaccination, and challenge. Hamsters will be sequentially infected with two different influenza viruses, and subsequently vaccinated with an inactivated vaccine. The B cell responses elicited will be compared to those of human samples obtained before and after vaccination with the same vaccine strain that will be used to vaccinate the hamsters. In another study, hamsters will be sequentially infected with two different influenza viruses, and subsequently vaccinated with an investigational (potentially broadly protective) vaccine and challenged with a heterologous virus. The B cell immune responses elicited will be compared with those from a Phase 2a clinical trial that used the same investigational vaccine and challenge viruses. By leveraging our preliminary data and our access to human samples, we will address several key topics of PAR-19-248, including the assessment of novel animal models, the assessment of aerosol exposure and pre-exposure to influenza viruses on immune responses, and the recapitulation of immune mechanisms such as imprinting and back-boosting in animal models.

项目摘要 为了促进NIAID的战略计划，以开发通用影响者疫苗，Par-19-248固体 “研究项目旨在提高动物模型的预测价值，以概括人类免疫力 流感感染和疫苗接种。 248通过继续我们发展金叙利亚仓鼠（以下称为仓鼠）作为动物 影响力病毒研究模型。这是基于我们以前的发现，即影响力病毒的组成 仓鼠呼吸道中的受体与人类的呼吸道相似，并且人类 流感病毒在仓鼠的呼吸道中复制，包括最近的人类H3N2影响病毒， 在小鼠中不会有效复制。在特定目标1中，我们计划建立影响病毒气溶胶 仓鼠的曝光平台。目前，大多数影响病毒感染研究需要鼻内病毒 接种，这不是自然感染途径（即气溶胶暴露）。通过建立气雾剂 仓鼠的曝光平台，我们正在谈论一个Par-19-248的关键主题。在特定目标2中，我们将评估 仓鼠在模拟首次影响病毒对的影响时的预测价值 随后的暴露（印迹）。除少数例外，影响病毒感染和疫苗接种研究 已经在幼稚的动物中进行了 通过感染和/或疫苗受到多种影响。在这里，我们将依次感染 仓鼠（通过鼻内感染或气溶胶暴露）具有相同的人类影响 儿童的第一和第二感染（基于我们从小儿队列获得的临床样本 学习）。然后，将比较仓鼠和人类血清的B细胞对第一和第二感染的反应。 在特定目标3中，我们将评估仓鼠在模拟人类免疫调查中的预测价值 多种感染，疫苗接种和挑战。仓鼠将依次感染两种不同的 流感病毒，随后被灭活的疫苗接种。引起的B细胞响应将是 与在疫苗之前和之后获得的人类样品的疫苗相同的疫苗应变相比 将用于接种仓鼠。在另一项研究中，将仓鼠依次感染两种不同的 影响力病毒，随后通过研究（潜在受到广泛保护的）疫苗接种疫苗 并受到异源病毒的挑战。将引起的B细胞免疫反应与那些反应进行比较 从使用相同研究疫苗和挑战病毒的2A期临床试验中。通过利用 我们的初步数据和对人类样本的访问，我们将讨论PAR-19-248的几个关键主题， 包括对新型动物模型的评估，气溶胶暴露的评估和暴露于 影响因素对免疫反应的影响，以及诸如印记和 在动物模型中进行反击。

项目成果

Immunogenicity and efficacy of XBB.1.5 rS vaccine against EG.5.1 variant of SARS-CoV-2 in Syrian hamsters.

XBB.1.5 rS 疫苗针对叙利亚仓鼠中 SARS-CoV-2 EG.5.1 变体的免疫原性和功效。

• DOI: 10.21203/rs.3.rs-3873514/v1
• 发表时间: 2024
• 期刊: Research square
• 作者: Boon,Jacco;Soudani,Nadia;Bricker,Traci;Darling,Tamarand;Seehra,Kuljeet;Patel,Nita;Guebre-Xabier,Mimi;Smith,Gale;Suthar,Mehul;Ellebedy,Ali;Davis-Gardner,Meredith
• 通讯作者: Davis-Gardner,Meredith