Antibody Discovery Platform

Sung



Antibody Discovery Platforms

  1. Phage Display Technology:
    • Phage display is a versatile technique that involves expressing peptide or protein libraries on the surface of bacteriophages (viruses that infect bacteria). This method is used for screening large libraries of variants to identify those that bind with high affinity to specific targets.
  2. Yeast Display:
    • Similar to phage display, yeast display involves expressing the antibody libraries on the surface of yeast cells. This method is beneficial for screening because of the eukaryotic post-translational modifications that yeast can perform, which are important for the function of many antibodies.
  3. Single B Cell Technologies:
    • This approach involves isolating individual B cells (the cells responsible for antibody production in the immune system) to capture and sequence the antibody genes they produce. Technologies like microfluidics and single-cell sequencing have enhanced the throughput and precision of this method.
  4. Next-Generation Sequencing (NGS):
    • NGS of the B-cell receptor repertoire allows for an in-depth analysis of the diversity of antibody responses. This method can generate vast amounts of data on the sequence variability in the immune response, aiding in the identification of highly effective antibodies.
  5. Transgenic Mice:
    • These are mice genetically engineered to produce human antibodies when exposed to an antigen. This technology allows for the generation of fully human antibodies directly in a living organism, which can then be further tested and developed for therapeutic use.
  6. Mass Spectrometry-Based Antibody Profiling:
    • Advanced mass spectrometry techniques are now being used to analyze the structure and function of antibodies at a molecular level. This helps in understanding the complex structure of antibody-antigen interactions and improves the selection of candidates with the best therapeutic potential.
  7. Artificial Intelligence and Machine Learning:
    • AI and machine learning are increasingly being integrated into antibody discovery platforms to predict antibody structures, optimize antibody-antigen interactions, and enhance the selection process for potential therapeutic antibodies.

BCR-seq

  1. Clonotype Identification:
    • The primary goal in analyzing BCR-seq data is to identify clonotypes, which are unique BCR sequences that can indicate clonal expansions in response to specific antigens. Advanced bioinformatics tools are used to assemble these sequences from short reads, identify the variable (V), diversity (D), and joining (J) gene segments, and annotate the complementarity-determining region 3 (CDR3), crucial for antigen specificity.
  2. Diversity Analysis:
    • BCR-seq allows for the measurement of repertoire diversity, which is key to understanding the breadth of the immune response. Metrics such as diversity indices and clonal richness can be calculated to assess how broad or focused the immune response is.
  3. Somatic Hypermutation Analysis:
    • Analyzing the patterns and rates of somatic hypermutations within BCR sequences helps in understanding how B cells evolve to refine their affinity for antigens. This aspect is particularly important in chronic infections and cancer, where ongoing antigen stimulation is prevalent.
  4. Longitudinal Monitoring:
    • BCR-seq can be performed over time to monitor changes in the B-cell repertoire in response to interventions such as vaccination, infection, or autoimmune disease progression. This longitudinal analysis can reveal how the immune repertoire adapts over time.

Utility of BCR-seq

  1. Vaccine Development:
    • BCR-seq is extensively used in vaccine research to identify the characteristics of protective antibodies. This information can guide the design of vaccines that elicit potent and broad immune responses.
  2. Cancer Immunotherapy:
    • In cancer, BCR-seq is used to explore the diversity and dynamics of tumor-infiltrating B cells, which can contribute to anti-tumor immunity. Understanding BCRs in the tumor microenvironment can help in designing B cell-mediated immunotherapeutic strategies.
  3. Autoimmune Disease Research:
    • By identifying autoreactive clonotypes, BCR-seq helps in understanding the etiology of autoimmune diseases and can contribute to the development of targeted therapies that modulate harmful immune responses.
  4. Infection Response Analysis:
    • BCR-seq is critical in studying the evolution of the immune response during infection, particularly for rapidly evolving viruses. This can inform treatment strategies and provide insights into immune evasion mechanisms.
  5. Diagnostic Tool:
    • BCR-seq has potential as a diagnostic tool, particularly in immunodeficiency disorders, by assessing the health and diversity of the immune repertoire.

BCR-seq analysis tools