THE CONVALESCENT SERUM

 

 

 Monoclonal antibody therapy is a cornerstone of modern care for noncommunicable diseases, such as cancer, autoimmune diseases, and cardiovascular disease. But long before the identification, isolation or cloning of antibodies, passive transfer of immune serums was used as a treatment for infectious diseases, specifically tetanus and diphtheria, which were otherwise often lethal. Even today, the antiserum of convalescent donors is being explored as a possible therapeutic intervention against viral infections, including those caused by Ebolavirus and sarS-CoV-2 pandemic.

    However, the therapeutic potential of immune serums was first demonstrated more than 100 years ago in a series of animal experiments that evaluated immunity to bacterial pathogens Clostridium tetani and Corynebacterium diphtheriae and their respective toxins. In 1890, Emil von Behring and Shibasaburo Kitasato reported that total blood or cell-free serum from a rabbit previously injected with C. tetani could protect infected mice with a lethal dose of tenic bacilli. In addition, prior treatment of bacterial filtrate containing tetanus toxin with serum from an immunized rabbit blocked its lethality when injected later into mice. His historical findings included that: the cell-free components of a rabbit immune to tetanus had properties that could destroy the toxin; these properties were missing from the blood of animals that had not received tetanus; the components that inactivate tetanus could be transferred in a stable manner to animals infected with C. tetani by transfusion, in which they exerted a therapeutic effect.

    A week after the report of these results, Behring published a related paper that analyzed Immunity to C. diphtheriae in animals in which he demonstrated that the transfer of antiserums from immunized rats protected guinea pigs injected with diphtheria toxin. These findings set the stage for what was called serum therapy, the transfer of serums from an immunized donor to a naive recipient to treat an infectious disease, and for which von Behring received the first Nobel Prize in Physiology or Medicine in 1901.

     In 1894, the success of serum therapy in humans was first reported in children with diphtheria, a disease that accounted for 1% of all deaths of children under the age of 5 at the time. When antiserum treatment was started shortly after diagnosis, nearly 100% of children recovered. A short time later, tetanus prevention was achieved through the use of horse antiserums, which became the primary therapy of wounded soldiers during World War I to prevent what had previously been a lethal disease. These successes with passive serum therapy also served to drive the research community to develop vaccine strategies that would actively cause protective antibodies naturally generated during infection.

   The discovery that immunization with a bacterial pathogen or product could cause a serum substance with toxin neutralizing properties, and that we now know they are antibodies, provided some of the first ideas about humoral immunity that could explain the results of vaccination, as observed by Edward Jenner 100 years earlier. Clarification of the effects of antiserums helped to understand hypersensitivity (observed due to the use of animal antiserums in humans) and the development of active vaccination for infectious diseases. Demonstrating therapeutic efficacy through serum therapy is the basis of current antibody-based immunotherapy.