RAPID: Immunogenicity of SARS-CoV2 to Human T Cells

RAPID：SARS-CoV2 对人类 T 细胞的免疫原性

• 批准号: 2026995
• 负责人: Arup Chakraborty
• 金额: $ 12.45万
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2026995&HistoricalAwards=false
• 关键词: RAPID; Immunogenicity; SARS; CoV2; Human

Pandemics caused by infectious pathogens have plagued humanity since antiquity. The Coronavirus Disease 2019 (COVID-19) caused by the SARS-CoV-2 virus is currently spreading across the world rapidly, including in the United States, with major adverse impact on health and the economy. The SARSCoV-2 outbreak has led to several urgent efforts to develop vaccines that may offer protection against this virus. It is unknown as to whether the current approaches being pursued will elicit protective immune responses in humans. While vaccines have been very effective against many pathogens, the empirical methods for vaccine development pioneered by Pasteur and Jenner over two centuries ago have failed to produce effective vaccines against Human Immune Deficiency Virus, Malaria, Tuberculosis, and many other pathogens. Therefore, rational design of vaccines based on a mechanistic understanding of the pertinent virology and immunology is being pursued, and these efforts include work that is rooted in statistical physics. SARSCoV-2 is phylogenetically most similar to SARS-CoV. This project will use a machine learning approach to understand how the SARS-CoV-2 virus interacts with the immune T cells. This work will directly impact the design of SARS-CoV-2 vaccines and vaccines against future endemic-causing pathogens.Analyses of patients who have recovered from SARS-CoV shows that antibody responses are not prevalent a few years later, but memory T cell responses are durable and may offer long-term protection. The main questions addressed by this project are 1. Will the SARS-CoV peptides targeted by human T cells that are mutated in SARS-CoV-2 still elicit human T cell responses - i.e. are they immunogenic? 2: Are the 102 peptides identified by host major histocompatibility molecules binding assays alone that are common between SARS-CoV and SARS-CoV-2 immunogenic in humans? If not, they are irrelevant from vaccine design perspective. The goal of the work proposed here is to take a physics-based machine learning approach to determine the immunogenicity of SARS-CoV-2 proteins to human T cell responses.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

自古以来，传染性病原体引起的流行病一直困扰着人类。由 SARS-CoV-2 病毒引起的 2019 年冠状病毒病（COVID-19）目前正在世界范围内迅速传播，其中包括美国，对健康和经济产生了重大不利影响。 SARSCoV-2 的爆发引发了多项紧急努力，以开发可针对该病毒提供保护的疫苗。目前尚不清楚目前正在采用的方法是否会在人类中引发保护性免疫反应。虽然疫苗对许多病原体非常有效，但巴斯德和詹纳在两个多世纪前开创的疫苗开发经验方法未能生产出针对人类免疫缺陷病毒、疟疾、结核病和许多其他病原体的有效疫苗。因此，人们正在追求基于对相关病毒学和免疫学的机械理解的疫苗的合理设计，这些努力包括植根于统计物理学的工作。 SARSCoV-2 在系统发育上与 SARS-CoV 最相似。该项目将使用机器学习方法来了解 SARS-CoV-2 病毒如何与免疫 T 细胞相互作用。这项工作将直接影响 SARS-CoV-2 疫苗和针对未来流行病原体的疫苗的设计。对 SARS-CoV 康复患者的分析表明，几年后抗体反应并不普遍，但记忆 T 细胞反应是持久的，可能提供长期保护。该项目要解决的主要问题是 1. SARS-CoV-2 中突变的人类 T 细胞靶向的 SARS-CoV 肽是否仍会引起人类 T 细胞反应 - 即它们是否具有免疫原性？ 2：仅由宿主主要组织相容性分子结合测定鉴定出的 102 种肽是否在人类 SARS-CoV 和 SARS-CoV-2 免疫原性之间常见？如果不是，从疫苗设计的角度来看它们就无关紧要。这里提出的工作目标是采用基于物理的机器学习方法来确定 SARS-CoV-2 蛋白对人类 T 细胞反应的免疫原性。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Inferring the intrinsic mutational fitness landscape of influenzalike evolving antigens from temporally ordered sequence data

从时间顺序序列数据推断流感样进化抗原的内在突变适应性景观

• DOI: 10.1103/physreve.105.024401
• 发表时间: 2022
• 期刊: Physical Review E
• 影响因子: 2.4
• 作者: Doelger, Julia;Kardar, Mehran;Chakraborty, Arup K.
• 通讯作者: Chakraborty, Arup K.

Learning from HIV-1 to predict the immunogenicity of T cell epitopes in SARS-CoV-2.

• DOI: 10.1016/j.isci.2021.102311
• 发表时间: 2021-04-23
• 期刊: iScience
• 影响因子: 5.8
• 作者: Gao A;Chen Z;Amitai A;Doelger J;Mallajosyula V;Sundquist E;Pereyra Segal F;Carrington M;Davis MM;Streeck H;Chakraborty AK;Julg B
• 通讯作者: Julg B

Population extinction on a random fitness seascape

随机适应度海景上的种群灭绝

• DOI: 10.1103/physreve.102.052106
• 发表时间: 2020
• 期刊: Physical Review E
• 影响因子: 2.4
• 作者: Ottino-Löffler, Bertrand;Kardar, Mehran
• 通讯作者: Kardar, Mehran