As with monoclonal antibody drugs, the generation of polyclonal antibody drugs begins by inoculating an animal with a specific antigen to elicit an immune response (Figure 1 – bottom panel). Depending on the polyclonal antibody drug that is being produced, the antigen needs to be carefully selected.
Antigens can include a wide variety of substances such as peptides, viruses and cells. In accordance with a natural immune response, a heterogeneous mixture of antibodies is produced, which is then extracted from the animal’s serum. These polyclonal antibodies are capable of binding multiple epitopes on a single antigen and, for this reason, they have an increased overall affinity against the antigen of interest compared to monoclonal antibody drugs.
As a result of the inherent variation within polyclonal antibody drugs, they display greater tolerance to minor changes in the target antigen, which might occur through polymorphisms and glycosylation. Moreover, polyclonal antibody drugs are favored for their shorter production times and lower production costs compared to their monoclonal counterparts, although they possess greater batch-to-batch variability.
Polyclonal antibody drugs were once administered to treat pneumonia, scarlet fever, and meningococcal meningitis3, however, the introduction and rapid development of vaccines, antibiotics, and use of monoclonal antibody therapies — in conjunction with the inherent limitations of polyclonal antibodies — have led to decreased usage of polyclonal antibody drugs.
Nonetheless, a number of animal-derived polyclonal antibody drugs are still marketed, including immunosuppressive therapies and antivenoms3. The latter is particularly relevant as passive immunization or polyclonal antibody therapy remains the main and sometimes only treatment. Moreover, human-derived polyclonal antibody drugs are available as prophylactics against tetanus and cytomegalovirus disease, as well as for passive protection to hepatitis B, to name a few applications3.
Figure 1. Illustration of the stages in the production of monoclonal antibodies through hybridomas (top panel) and polyclonal antibodies (bottom panel).