Immunological drivers of the transition from epidemicity to endemicity of SARS-CoV-2 in a high transmission LMIC setting

高传播中低收入国家环境中 SARS-CoV-2 从流行病转变为地方病的免疫驱动因素

• 批准号: 10577684
• 负责人: Federico Costa
• 金额: $ 75.8万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-21 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10577684
• 关键词: 2019-nCoV; Address; Affect; Antibodies; Antibody Response; Antibody titer measurement; Antigens; Attenuated; Bayesian Analysis; Biological Assay; Brazil; COVID-19 vaccination; Cellular Immunity; Cohort Analysis; Collaborations; Communities; Data; Development; Dimensions; Enzyme-Linked Immunosorbent Assay; Epidemic; Epidemiologic Methods; Epidemiology; Foundations; Future; Health; Histocompatibility Antigens Class II; Humoral Immunities; Hybrids; Immune; Immune response; Immunity; Immunize; Immunologics; Individual; Infection; Infection prevention; Investments; Literature; Maps; Mass Vaccinations; Measurement; Measures; Mucous Membrane; Nested Case-Control Study; Outcome; Output; Participant; Phase; Play; Policies; Population; Preparation; Prospective cohort; Public Health; Recording of previous events; Research Design; Risk; Risk Reduction; Role; SARS coronavirus; SARS-CoV-2 P.1; SARS-CoV-2 antibody; SARS-CoV-2 immunity; SARS-CoV-2 infection; SARS-CoV-2 variant; Serology; Serum; Severities; Shapes; Slow-Wave Sleep; Slum; Surveys; Symptoms; Time; Vaccination; Vaccines; Variant; Virus; Work; analytical method; biobank; case finding; cohort; evidence base; experience; flexibility; follow-up; immunological status; infection rate; infection risk; insight; low and middle-income countries; mortality; neutralizing antibody; novel; novel strategies; novel vaccines; pandemic disease; pathogen; response; tool; transmission process; vaccination strategy; viral transmission

PROJECT SUMMARY Although new variants may contribute to surges, we expect SARS-CoV-2 to transition to a new phase where the virus continues to circulate but at lower levels. Sequential immunizing exposures, whether due to infection or vaccination, have transformed the immune status of populations by cumulatively increasing antibody levels and increasing the breadth of antigenic targeting of SARS-CoV-2 by antibodies. The relative role of increased magnitude of antibody responses or broadening of antigenic recognition of SARS-CoV-2 in protecting populations from infection is not known. Strikingly, though mucosal responses have been found to play key roles in protecting individuals from infection, SARS-CoV-2 literature has focused almost exclusively on serological responses. Effective policy and investment in public health measures as the pandemic continues will require information on the relative importance of specific immune responses. Gathering evidence in diverse settings including low and middle income countries (LMIC) is particularly important as the immunizing exposure history in these settings has been different (in terms of infections and vaccine use) and a smaller evidence base is available from these settings. Our proposed work seeks to continue to interrogate SARS-CoV-2 immunity in a cohort residing in an urban slum community in Brazil which we have followed since 2003. We identified an extraordinarily high SARS-CoV-2 attack rate (75%) during two epidemic waves with D614G and Gamma variants. Subsequent vaccination has generated hybrid immunity in a large proportion of our cohort. Our proposed study would investigate the relative role of antibody magnitude and breadth within systemic and mucosal compartments in protecting this population from infection. To accomplish this, we propose to conduct serologic and virologic surveillance in this community and develop tools to interpret serological measures of infection that address a key epidemiological challenge for the world in continued characterization of infection during the next phase of the pandemic. Our proposal leverages a 27-year scientific collaboration with the Brazilian Ministry of Health, an extensive track record of interrogating SARS-CoV-2 immunity, novel assays and analytical methods to infer infection histories and characterize multi-antigen immune responses. Our study will generate key evidence to inform the development of novel vaccines (intranasal, multi-antigen) and a new approach to tracking SARS-CoV-2 infections in populations with pre-existing immunity where symptom-based virologic surveillance may give an insufficient view of viral transmission.

项目概要 尽管新变种可能会导致病例激增，但我们预计 SARS-CoV-2 将过渡到一个新阶段，其中 病毒继续传播，但水平较低。连续免疫暴露，无论是否由于感染 或疫苗接种，通过累积增加抗体水平改变了人群的免疫状态 扩大抗体针对 SARS-CoV-2 的抗原靶向范围。相对作用增加 SARS-CoV-2 的抗体反应强度或抗原识别范围的扩大在保护中的作用 感染人群尚不清楚。引人注目的是，尽管粘膜反应被发现起着关键作用 SARS-CoV-2 文献几乎完全集中在保护个人免受感染方面的作用 血清学反应。随着疫情的持续，有效的公共卫生措施政策和投资 将需要有关特定免疫反应的相对重要性的信息。收集不同方面的证据 包括低收入和中等收入国家 (LMIC) 在内的环境尤为重要，因为免疫暴露 这些环境中的历史不同（在感染和疫苗使用方面）并且证据较小 基础可从这些设置中获得。我们提议的工作旨在继续探究 SARS-CoV-2 我们自 2003 年以来一直跟踪居住在巴西城市贫民窟社区的一群人的免疫力。我们 在两次流行浪潮中，D614G 和 伽玛变体。随后的疫苗接种在我们的大部分人群中产生了混合免疫。 我们提出的研究将调查抗体大小和广度在系统和免疫系统中的相对作用。 粘膜区室保护该人群免受感染。为了实现这一目标，我们建议进行 该社区的血清学和病毒学监测，并开发工具来解释血清学测量 在持续描述感染特征方面解决世界面临的一个关键流行病学挑战的感染 在大流行的下一阶段。我们的提案利用了与 27 年的科学合作 巴西卫生部，对 SARS-CoV-2 免疫力的广泛跟踪记录，新颖的检测方法 以及推断感染史和表征多抗原免疫反应的分析方法。我们的研究 将产生关键证据，为新型疫苗（鼻内、多抗原）和新疫苗的开发提供信息 在基于症状的情况下追踪具有预先存在免疫力的人群中的 SARS-CoV-2 感染的方法 病毒学监测可能无法充分了解病毒传播情况。