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.

项目摘要 新兴的严重急性呼吸道综合征冠状病毒2（SARS-COV-2）的变体 全球对现有疫苗和未来疫苗有效性的挑战。这个项目将解决问题 围绕对不同SARBECOVIRUS暴露模式的免疫学反应，对 通过对独特人群进行纵向反复监视，开发疫苗 以前确定要高度暴露于与SARS-COV-2相关的冠状病毒多样性 缅甸。有及时的机会跟随这些社区，尤其是紧随其后的 SARS-COV-2感染和/或疫苗以了解哪些先前的SARBECOVIRUS暴露模式 扩大中和抗体的发展可能性。我们将评估 自然和疫苗接种基于SARBECOVIRUS暴露对潜水员模式的影响对PAN的发展 SARBECOVIRUS通过遵循三个特定的人类群体中和抗体：（1）大象记录仪 在主动森林砍伐过程中，从事丛林狩猎（包括蝙蝠和穿衣） 缅甸剩下的柚木森林，（2）蝙蝠鸟粪收获Hpaan Cave Systems周围的社区 在Kayin State和（3）以前未投资的人群从事喀斯特宗教活动 DAWNA范围内的洞穴系统。特定抗体反应的上蜡和减弱将是 随着时间的流逝，通过使用这些人群的流行前存档标本并重复 前瞻性抽样。我们将利用一种新型Luminex珠子的多质子SARBECOVIRUS分析，能够 简单地检测到针对21种不同HACE2结合SARBECOVIRAS的中和抗体的中和抗体。 将确定对特定SARBecovirus的暴露模式，并评估其病毒特征 对开发泛核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的可塑性（宿主物种的广度已知病毒感染）。 先前天然SARBECOVIRUS暴露的模式以及天然SARS-COV-2感染和 /或 然后，将评估疫苗接种对广泛反应性抗体反应的贡献。生成的数据 通过该项目将告知潜在的交叉SARBECOVIRUS进化枝疫苗接种策略，以保护可以保护 针对已知和未来的新兴SARS-COV-2变体。我们还将进行深入 研究有助于人畜共患病毒的行为风险因素，这将有助于 在这个至关重要的生态区域中，冠状病毒出现的缓解策略。