Single cell RNA and immune repertoire profiling of COVID-19 patients reveal novel neutralizing antibody

  • PDF / 1,666,619 Bytes
  • 5 Pages / 595.276 x 785.197 pts Page_size
  • 87 Downloads / 159 Views

DOWNLOAD

REPORT


Protein & Cell

HIGHLIGHT Single cell RNA and immune repertoire profiling of COVID-19 patients reveal novel neutralizing antibody

1

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China 2 School of Life Science and Technology, Harbin Institute of Technology, Harbin 150000, China 3 Harbin Sixth Hospital, Harbin 150000, China 4 Key Laboratory of Biological Big Data (Harbin Institute of Technology), Ministry of Education, Harbin 150001, China & Correspondence: [email protected] (P. Wang), [email protected] (Z. Bu), [email protected] (Q. Jiang) Accepted October 29, 2020

There is no doubt that COVID-19 outbreak is currently the biggest public health threat, which has caused catastrophic consequences in many countries and regions. As host immunity is key to fighting against virus infection, it is important to characterize the immunologic changes in the COVID-19 patients, and to explore potential therapeutic candidates. The most efficient ways to end this pandemic are to vaccinate the susceptible population, and to use specific drugs, such as monoclonal antibodies against the viral spike protein (S protein), to treat the affected individuals. Several promising neutralizing antibodies have recently been reported (Cao et al., 2020; Lv et al., 2020). However, no antibody drug against COVID-19 has been approved yet in the world. Against the rapidly evolving SARS-CoV-2 virus, a cocktail of several non-competing antibodies may reach to the maximum treatment effect (Cai et al., 2020). Therefore, developing new potential antibodies remain be highly valuable. Early-stage recovery patients maintain various immune responses and possess abundant protective antibodies in the circulation (Thevarajan et al., 2020). Therefore, we conducted a joint analysis using single cell transcriptome

Fang Li, Meng Luo, Wenyang Zhou, and Jinliang Li have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13238-020-00807-6) contains supplementary material, which is available to authorized users.

© The Author(s) 2020

sequencing (scRNA-seq), single cell BCR sequencing (scBCR-seq) and deep BCR repertoire profiling to prioritize the therapeutically relevant neutralizing antibody sequences in patients who have recently cleared the virus. Fresh blood samples were collected from a total of 16 COVID-19 patients at the time of hospital discharge (Table S1 and Supplementary Materials). PBMCs were divided into three aliquots for separate data generation: 1) single cell RNA sequencing, 2) single cell BCR V(D)J sequencing and 3) deep BCR repertoire sequencing (Fig. 1A and Table S1). In total, we obtained single cell 5′V(D)J sequencing data from 88,974 immune cells (Table S2) and immune receptor hypervariable regions from 6.9 million BCR clones (Table S3). To reveal the changes of immune cells caused by SARSCoV-2 infection, 8 healthy controls with single cell transcriptome data profiled