Investigation of sarbecovirus exposure patterns and development of pan-SARS-CoV-2 neutralizing antibody responses in high-risk cohorts in Myanmar

缅甸高危人群中 sarbecovirus 暴露模式的调查和泛 SARS-CoV-2 中和抗体反应的发展

• 批准号: 10646897
• 负责人: Tierra Smiley Evans
• 金额: $ 20.49万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-06 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646897
• 关键词: 2019-nCoV; Age; Antibody Response; Behavior; Behavioral; Binding; Biological; Biological Assay; COVID-19 pandemic effects; Characteristics; Chiroptera; Communities; Coupled; Data; Deforestation; Development; Effectiveness; Elephants; Exposure to; Frequencies; Funding; Future; Harvest; Human; Immune response; Immunization Programs; Individual; Infection; Investigation; Medical History; Myanmar; Pattern; Phenotype; Population; Process; Public Health; Religion; Risk Behaviors; Risk Factors; SARS coronavirus; SARS-CoV-2 infection; SARS-CoV-2 infection history; SARS-CoV-2 variant; Sampling; Sarbecovirus; Serum; Specimen; Surveys; System; Time; USAID; United States National Institutes of Health; Vaccination; Vaccines; Viral; Virus; Waxes; Work; Zoonoses; biological specimen archives; cohort; exposed human population; forest; high risk; high risk behavior; neutralizing antibody; novel; novel coronavirus; post SARS-CoV-2 infection; pre-pandemic; prospective; vaccination strategy; vaccine development; vaccine strategy; variants of concern; virus genetics

PROJECT SUMMARY Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern pose a global challenge to the effectiveness of existing and future vaccines. This project will address questions surrounding the immunological response to different sarbecovirus exposure patterns with implications for vaccine development by conducting longitudinal repeated surveillance of unique human populations, previously determined to be highly exposed to a diversity of SARS-CoV-2-related coronaviruses in Myanmar. There is a timely opportunity to follow these communities, particularly immediately following SARS-CoV-2 infection and/or vaccination to understand which previous sarbecovirus exposure patterns expand the likelihood of development of pan-sarbecovirus neutralizing antibodies. We will evaluate the impact of diverse patterns of natural and vaccination-based sarbecovirus exposure on development of pan- sarbecovirus neutralizing antibodies by following three specific human cohorts: (1) elephant loggers engaged in bushmeat hunting (including bats and pangolins) during the process of active deforestation of Myanmar’s remaining teak forests, (2) bat guano harvesting communities surrounding HpaAn cave systems in Kayin State and (3) a previously uninvestigated population engaged in religious activities within the Karst cave systems in the Northern Dawna range. Waxing and waning of specific antibody responses will be followed over time through use of pre-pandemic archived specimens from these populations and repeated prospective sampling. We will utilize a novel Luminex bead-based multi-plex sarbecovirus assay, capable of simultaneously detecting neutralizing antibodies against 21 different hACE2-binding sarbecoviruses. Exposure patterns to specific sarbecoviruses will be identified and viral characteristics evaluated for their contribution to the likelihood of developing pan-sarbecovirus antibody responses, including viral genetic and functional phenotypic similarity and host plasticity (breadth of host species a virus is known to infect). Patterns of prior natural sarbecovirus exposure coupled with natural SARS-COV-2 infection and / or vaccination will then be evaluated for contributions to broadly reactive antibody responses. Data generated through this project will inform on potential cross sarbecovirus clade vaccination strategies that could protect against both known and future emerging SARS-CoV-2 variants. We will also conduct an in-depth investigation of behavioral risk factors contributing to zoonotic sarbecovirus spillover that will aid in mitigation strategies in this critically important ecological region for coronavirus emergence.

项目概要 新出现的严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 变种值得关注，引起了人们的关注 该项目将解决现有和未来疫苗有效性的全球挑战。 围绕不同 sarbecovirus 暴露模式的免疫反应及其影响 通过对独特人群进行纵向重复监测来开发疫苗， 先前确定高度暴露于多种 SARS-CoV-2 相关冠状病毒 缅甸有一个及时的机会来关注这些社区，特别是紧随其后。 SARS-CoV-2 感染和/或疫苗接种，以了解以前的 sarbecovirus 暴露模式 扩大开发泛sarbecovirus中和抗体的可能性我们将评估 自然和基于疫苗接种的沙贝克病毒暴露的不同模式对泛型疾病发展的影响 以下三个特定人类群体产生了 sarbecovirus 中和抗体：(1) 大象伐木工 在积极砍伐森林的过程中从事丛林肉狩猎（包括蝙蝠和穿山甲） 缅甸剩余的柚木林，(2) HpaAn 洞穴系统周围的蝙蝠鸟粪采集社区 克伦邦和 (3) 以前未经调查的在喀斯特地区从事宗教活动的人口 北道纳山脉的洞穴系统的特异性抗体反应将会增减。 随着时间的推移，通过使用这些人群的大流行前存档样本进行跟踪，并重复 我们将利用一种新型的基于 Luminex 珠的多重 sarbecovirus 检测。 同时检测针对 21 种不同的 hACE2 结合 sarbecovirus 的中和抗体。 将确定特定 sarbecovirus 的暴露模式并评估其病毒特征 对产生泛沙病毒抗体反应的可能性的贡献，包括病毒遗传和 功能表型相似性和宿主可塑性（已知病毒感染的宿主物种的广度）。 先前自然 sarbecovirus 暴露与自然 SARS-COV-2 感染的模式和/或 然后将评估疫苗接种对广泛反应性抗体反应的贡献。 通过该项目将提供有关潜在的交叉 sarbecovirus 分支疫苗接种策略的信息，这些策略可以保护 我们还将针对已知和未来出现的 SARS-CoV-2 变种进行深入研究。 调查导致人畜共患沙贝克病毒溢出的行为风险因素，这将有助于 这个对于冠状病毒出现至关重要的生态区域的缓解策略。