Hyperimmune Globulin

If convalescent plasma proves effective in managing COVID-19 disease, the next logical step is to produce the concentrated antibody product generally referred to as hyperimmune globulin or sometimes as polyclonal antibodies.   Both convalescent plasma and immune globulins are ways of creating passive immunity.  By transferring pre-formed antibodies to people at risk or suffering from disease, they provide short-term protection, lasting as long as the externally formed antibodies are retained in the body, which is generally measured in weeks or a few months.  This is to be contrasted with the active immunity created by vaccines which stimulate the individual’s own immune system to produce antibodies to the antigen in the vaccine.

Concentrated antibody treatment in humans dates back to 1894, making it one of the oldest effective medical treatments known.  The diphtheria antitoxin had been identified by Roux and Yersin in France in 1888, and in 1890, von Behring and Kitasato, working in Germany, showed that serum from animals who had been injected with the diphtheria bacillus protected other animals exposed to the disease, particularly if used early in the course of the illness. 

The first use in humans was in Europe, where an 1894 outbreak of diphtheria was controlled with serum derived from experimental animals, and soon afterwards industrial scale production of diphtheria and tetanus antibodies produced by antigenic stimulation of large animals (horses, cows, sheep) quickly became the standard approach to treating these two diseases all over the developed world.  

This approach was applied to a number of other infectious diseases, most notably rabies, tetanus, pneumococcal pneumonia, measles and polio.  The peak use of these products was in the 1920’s and 1930’s, because the introduction of sulfonamides and antibiotics made their use to some extent redundant and their production fell for the next few decades. 

In the 1940’s the first use of human plasma to create antibodies was initiated, addressing hepatitis A (then called infectious hepatitis) and most, though not all, products used to produce passive immunity in the second half of the twentieth century have been of human origin.

The shift to humans reflected the concern that animal products contained non-human antigens that produced serum sickness and other forms of allergic reaction.  Additionally, for products of both human and animal origin, many purification steps have been added to eliminate contamination with other viruses to ensure better results. This enabled the development of safer preventative treatments for rabies, as well as immune globulins targeting viral infections such as hepatitis A and B, varicella–zoster virus and respiratory syncytial virus (RSV).

On this website, we post the protocol for a proposed trial of a COVID-19 immune globulin, a product which has yet to be created.  We thank Dr. Michael Oxman of the University of California, San Diego for sharing this protocol, the consent form and an informational document.