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Single-cell Omics Promotes Neutralizing Antibody Discovery and Immune Therapy Development for SARS-CoV-2

High-throughput single-cell sequencing has been applied to understand the diversity of the variable regions of heavy (VH) and light chains (VL) that determine the antigen specificity of antibodies. Developing neutralizing antibodies (NeutAbs) promises to be a fast and effective approach to block viral entry, fusion, or egress. Empowered by unrivaled expertise and advances in single-cell approaches, Creative Biolabs has developed integrated single-cell omics solutions to get the VH and VL sequences for antibodies from individual B cells and identify accurate VH and VL pairing to expedite neutralizing antibody discovery processes. In addition, single-cell solutions can advance the discovery of therapeutic targets and vaccines.

Neutralizing Antibodies Against SARS-CoV-2

NeutAbs provide important specific immune defense against SARS-CoV-2 infection by recognizing specific viral epitopes. Entry of SARS-CoV-2 into the host cell is mediated by the attachment of the viral spike (S) protein and angiotensin-converting enzyme 2 (ACE2) receptor. NeutAbs can block viral docking on ACE2 of host cells when they recognize the receptor-binding domain (RBD) on the S protein. Moreover, S protein-mediated viral fusion can be blocked by NeutAbs targeting the heptad repeat 2 (HR2) domain. In addition, NeutAbs have been shown to interact with other immune components, including complement, phagocytes, and natural killer (NK) cells to elicit effector responses for pathogen clearance.

Mechanism of the neutralizing antibodies against SARS-CoV-2.Fig.1 Mechanism of the neutralizing antibodies against SARS-CoV-2. (Zhou, 2020)

Single Cell Solutions for SARS-CoV-2 (COVID-19) Therapeutics Discovery

1. Single Cell Solutions for Therapeutic Targets Discovery

Based on the SARS-CoV-2 infection, single-cell solutions can be used to study the heterogeneity of the adaptive immune response, to analyze new immune cell subpopulations in health and disease, to explore potential cell surface markers and stage-specific pathogen antigens, to reveal the potential tropism of SARS-CoV-2, and to characterize phenotypic diversity before, during and after SARS-CoV-2 infection. All of these differences greatly promote the discovery of novel antiviral drugs and the development of potential immunomodulatory therapeutic strategies. Our single-cell solutions facilitating the discovery of therapeutic targets include but not limited to single-cell gene expression, single-cell immune profiling, single-cell ATAC, single-cell spatial gene expression.

2. Single Cell Solutions for Vaccine Discovery

Vaccines are among the most effective public health tools for combating certain infectious diseases such as SARS-CoV-2. Single-cell technology is opening up new possibilities for vaccine development for SARS-CoV-2 infection. Through characterizing transcriptional differences between functional immune responses, single-cell solutions provide a deeper understanding of functional mechanisms for the discovery of vaccine strategies and new therapeutic drug candidates for COVID-19. Especially, understanding of more predictive T cell potency is important for vaccine development.

3. Single Cell Solutions for Therapeutic NeutAbs Discovery

Single-cell technology is a critical approach to characterize the transcriptional changes and gene expression differences after SARS-CoV-2 infection. By studying immune repertoires of thousands of immune cells and elucidating the key anti-virus adaptive immune responses, you can rapidly generate a large and diverse panel of VH and VL sequences to yield fully recombinant antibodies with high target specificity.

  • Single-cell B-cell Receptor Sequencing (scBCR-seq)

    High-throughput scBCR-seq to obtain accurately paired full-length variable regions in a massively parallel fashion is a powerful tool for antibody discovery. As an important approach of single-cell biology, scBCR-seq can provide the difference and heterogeneity of immune responses, such as V(D)J gene sequences, paired α- and β-chain information, somatic hypermutation, etc.

  • Single-cell RNA Sequencing (scRNA-seq)

    scRNA-seq is a powerful tool that can provide the subtype, transcriptional state, and antibody sequence of single B cells. NeutAbs derived from these single B cells can then be cloned and characterized, thereby coupling the specificity of each B cell with its transcriptional program. scRNA-seq allows for the simultaneous exploration of the immune transcriptome, antibody-secreting cells heterogeneity, new immune cell subpopulations, and receptor functional characteristics at the single-cell level. Transcriptional profiling at the single B cell level provides new insights into the dynamic changes of virus infection and the complex interactions between viruses and host cells.

Schematic of single-cell B-cell receptor sequencing for antibody discovery.Fig.2 Schematic of single-cell B-cell receptor sequencing for antibody discovery. (Goldstein, 2019)

The discovery of novel antibodies to neutralize the virus is one of the important approaches to fight COVID-19. To better understand the new SARS-CoV-2 virus and explore novel and efficient NeutAbs, scientists at Creative Biolabs offer several different approaches to single-cell sequencing, ensuring that high-quality data meet the right needs. Our paired VH and VL repertoires largely expand immune repertoire sampling and expedite NeutAbs discovery processes. Our single-cell solutions can also maximize the success of your COVID-19 research in therapeutic targets discovery and vaccine discovery. If you have additional requirements or questions, please feel free to contact us.

References

  1. Zhou, G.; Zhao, Q. Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2. International Journal of Biological Sciences. 2020, 16(10): 1718.
  2. Goldstein, L. D.; et al. Massively parallel single-cell B-cell receptor sequencing enables rapid discovery of diverse antigen-reactive antibodies. Communications biology. 2019, 2(1): 1-10.
! ! For Research Use Only. Not for diagnostic or therapeutic purposes.

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