The Mechanical Advantage of Polyclonal Antibodies
To neutralize an antigen, like a virus or bacteria, antibodies are secreted by B cells in response to an unknown molecule being detected within an organism. Antibodies can be either monoclonal or polyclonal.
Monoclonal antibodies are created from identical B cells that are clones from a singular parent cell. They only recognize the same antigen epitope and have a monovalent affinity. These antibodies are created with tissue culture techniques and are produced ex vivo. They can take over six months to produce.
Polyclonal antibodies are produced from different B cell clones of the body and result in a heterogeneous mixture of antibodies. They are produced in vivo by injecting an animal with an immunogen, and the antibodies are collected straight from the blood serum after an animal shows a high enough antibody titer for the specific antigen. These antibodies are faster and cheaper to produce. The antibodies have a high affinity for the antigen because the heterogeneous solution will recognize multiple antibody epitopes.
Each antibody type has strong successes in different areas, but one is better suited than the other for responding to rapidly mutating viruses and other dynamic antigens. Polyclonal antibodies have a high affinity for antigens and can recognize more than a single epitope of an antigen. Positive treatment response is more likely to be seen with polyclonal antibodies, as they are tolerant of small changes in the target molecule structure. This tolerance translates to increased effectiveness for rapidly mutating viruses because the virus can still be recognized even after a mutation. A monoclonal antibody will not recognize or target a mutated virus.
Failing to use broad-spectrum polyclonal antibodies in diagnostic testing can result in disease detection suppression. Polyclonal antibodies have high-avidity binding, so antigen escape variants are less likely to occur. They also have a higher sensitivity for detecting proteins that are low-quality and are better for detecting native proteins. As a viral disease begins to spread in a population, there is a potential for the causative agent to mutate while still being an effective infectious agent.
Since monoclonal antibodies rely on a specific binding site, and polyclonal antibodies can attach at multiple sites on a target molecule, it is more likely that a polyclonal system will still detect the mutation. If detection testing relies only on monoclonal diagnostic procedures, early stages of the variant spread are likely to be missed, and the disease can continue to spread without proper control procedures for the person with the mutated strain.
This can be seen in practice with the rapidly mutating COVID-19 virus. Omicron, Delta, Alpha, and other coronavirus variants have created concern within the medical community and general population alike. Multiple monoclonal antibodies have been developed to target SARS-CoV-2, but their neutralization potential has decreased or disappeared completely with new variants.
Ultimately, polyclonal antibodies are necessary for effective and complete disease tracking. This is especially true when a disease is rapidly mutating and evolving.
