Antibodies, essential components of our immune system, are discovered through a variety of methods, evolving significantly over time.
Traditional Antibody Discovery
Traditionally, antibodies were discovered by immunizing experimental animals with a specific antigen. This process stimulates the animal's immune system to produce antibodies against that antigen. Subsequently, the animal's serum (blood plasma) is purified to isolate the antibody fraction. This method, although effective, yielded a polyclonal antibody mixture—a collection of antibodies recognizing different parts of the antigen. Emil von Behring and Shibasabura Kitasato's 1890 landmark work laid the groundwork for this approach. https://www.nature.com/documents/ni_focus_Milestones.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC5357605/ https://absoluteantibody.com/antibody-resources/antibody-overview/a-brief-history-of-antibodies/
Key Steps in Traditional Approach:
- Antigen Selection: Identifying and purifying the target antigen.
- Immunization: Injecting the antigen into an animal (e.g., mouse, rabbit).
- Serum Collection: Collecting blood samples from the immunized animal.
- Antibody Purification: Isolating the antibodies from the serum using techniques like affinity chromatography.
Modern Antibody Discovery Techniques
Modern techniques significantly improve upon the traditional methods by producing monoclonal antibodies (mAbs): identical antibodies targeting a single epitope (specific site) on the antigen.
- Hybridoma Technology: This Nobel Prize-winning technique fuses antibody-producing B cells with myeloma cells (immortal cancer cells) to create hybridomas. These hybridomas produce large quantities of a specific antibody. https://pmc.ncbi.nlm.nih.gov/articles/PMC5357605/
- Phage Display: This technique uses bacteriophages (viruses that infect bacteria) to display antibody fragments on their surface. This allows for the selection and amplification of antibodies with desired properties. https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-019-0592-z
- Next-Generation Sequencing (NGS): This high-throughput technology analyzes vast antibody repertoires to identify antibodies with specific properties. https://www.idtdna.com/pages/applications/antibody-discovery
Further advancements include using animals like llamas and sharks, known for producing smaller, more manageable antibodies (nanobodies). https://www.science.org/content/article/mini-antibodies-discovered-sharks-and-camels-could-lead-drugs-cancer-and-other-diseases Recent research highlights the surprising dual roles of antibodies, even extending to novel discoveries like antibodies neutralizing all COVID-19 variants. https://news.utexas.edu/2024/09/03/newly-discovered-antibody-protects-against-all-covid-19-variants/ https://midwestavidd.umn.edu/university-minnesota-scientists-discover-dual-roles-antibodies-covid-19-infections
