Predicted Cellular Immunity Population Coverage Gaps for SARS-CoV-2 Subunit Vaccines and Their Augmentation by Compact Peptide Sets.
Predicted Cellular Immunity Population Coverage Gaps for SARS-CoV-2 Subunit Vaccines and Their Augmentation by Compact Peptide Sets.
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DOI：
10.1016/j.cels.2020.11.010
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发表时间：
2021-01-20
期刊：
影响因子：
9.3
通讯作者：
Gifford DK
中科院分区：
文献类型：
--
作者：
Liu G;Carter B;Gifford DK
亚单位疫苗通过呈现病原体的一个成分来诱导对病原体的免疫，从而固有地限制了病原体肽在细胞免疫记忆中的表现。我们发现，在某些个体中，严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）亚基肽可能不会被主要组织相容性复合体（MHC）分子强有力地显示。我们介绍了一种亚单位疫苗的增强策略，即在疫苗中添加少量SARS-CoV-2肽，以提高病原体肽展示的人群覆盖率。我们的人口覆盖率估计整合了恢复期COVID-19患者肽免疫原性的临床数据和机器学习预测。我们评估了SARS-CoV-2的9个不同亚基的种群覆盖率，包括5个功能域和4个完整蛋白，并增加了每个亚基以填补预测的覆盖率缺口。临床数据和机器学习预测COVID-19亚基疫苗人群覆盖率缺口亚基增强可提高细胞免疫疫苗人群覆盖率预测无亚基肽疫苗具有较高的人群覆盖率基于COVID-19患者数据和机器学习的肽- hla免疫原性集成模型用于评估和设计COVID-19细胞免疫疫苗。预测了COVID-19亚单位疫苗的人口覆盖率差距，并提出了弥补这些差距的增强策略。紧凑的肽疫苗设计，不包括一个亚基，提出了良好的人口覆盖率。
Subunit vaccines induce immunity to a pathogen by presenting a component of the pathogen and thus inherently limit the representation of pathogen peptides for cellular immunity-based memory. We find that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit peptides may not be robustly displayed by the major histocompatibility complex (MHC) molecules in certain individuals. We introduce an augmentation strategy for subunit vaccines that adds a small number of SARS-CoV-2 peptides to a vaccine to improve the population coverage of pathogen peptide display. Our population coverage estimates integrate clinical data on peptide immunogenicity in convalescent COVID-19 patients and machine learning predictions. We evaluate the population coverage of 9 different subunits of SARS-CoV-2, including 5 functional domains and 4 full proteins, and augment each of them to fill a predicted coverage gap. Clinical data and machine learning predict SARS-CoV-2 peptide-HLA immunogenicity Human population coverage gaps of COVID-19 subunit vaccines are predicted Subunit augmentation improves vaccine population coverage for cellular immunity Subunit-free peptide vaccines are predicted to have high population coverage An integrated model of peptide-HLA immunogenicity based on data from COVID-19 patients and machine learning is used to evaluate and design COVID-19 vaccines for cellular immunity. Human population coverage gaps are predicted for COVID-19 subunit vaccines, and augmentation strategies are proposed to close these gaps. Compact peptide vaccine designs that do not include a subunit are presented that have good population coverage.
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DOI：
10.4049/jimmunol.1700893
发表时间：
2017-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jurtz V;Paul S;Andreatta M;Marcatili P;Peters B;Nielsen M
通讯作者：
Nielsen M
DOI：
10.1126/science.aam8825
发表时间：
2018-01-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ramsuran V;Naranbhai V;Horowitz A;Qi Y;Martin MP;Yuki Y;Gao X;Walker-Sperling V;Del Prete GQ;Schneider DK;Lifson JD;Fellay J;Deeks SG;Martin JN;Goedert JJ;Wolinsky SM;Michael NL;Kirk GD;Buchbinder S;Haas D;Ndung'u T;Goulder P;Parham P;Walker BD;Carlson JM;Carrington M
通讯作者：
Carrington M
影响因子：
5.4
作者：
Avadhanula, V;Rodriguez, CA;Adderson, EE
通讯作者：
Adderson, EE
影响因子：
9.3
作者：
O'Donnell, Timothy J.;Rubinsteyn, Alex;Laserson, Uri
通讯作者：
Laserson, Uri
影响因子：
9.3
作者：
Liu, Ge;Carter, Brandon;Gifford, David K.
通讯作者：
Gifford, David K.