Your immune system is your defense mechanism against bacteria, viruses, and other pathogens that find their way into your body. Active immunity is the body’s response to new antigens. The antibodies and other lymphocytes that are created during immune responses are typically permanent, meaning resistance to pathogens will typically remain intact. Your body maintains a memory of an infection and responds as necessary if it detects that specific antigen in the future.
Though active immunity is important for protection from illness, it does have a limitation: the time it takes your body to develop the antibodies. When you are exposed to an antigen for the first time, the invader will spread through your body unchecked for some time. This waiting period is the time it takes the body to identify the antigens and then create the specific antibodies for that antigen.
During that period, your body may be experiencing significant effects from the invading molecule. For example, being exposed to the rabies virus can cause death – very few humans have survived a rabies infection once it has taken hold. Part of the treatment, therefore, is the administration of rabies antibodies to begin fighting the virus even before the body has the chance to produce its own antibodies. This type of immunity is called passive immunity. Antibodies are introduced directly into the body from an external source. Passive immunity provides the body with a rapid response method that will decrease the severity of the infection or help you fight an illness you would not otherwise be able to fight. Unfortunately, this type of immunity is only temporary, lasting weeks or months, depending on the type, and does not cause the body to create its own defense system.
Passive Immunity with HIG Therapy
Polyclonal hyper immunoglobulin (HIG) therapy is a form of passive immunity administration. The therapy is derived from human or animal donors that have a high antibody titer against a desired antigenic target. It is a well-established and proven strategy by which immediate protection from a range of toxins is created in patients by transferring immunoglobulins. The HIG therapy is derived from polyclonal antibodies. They have a high avidity and broad specificity, and can bind to different sites on a pathogen. This therapy is administered until a patient develops a natural adaptive immune response or the pathogen is cleared.
There are more than 20 different FDA-approved HIG products that span a wide range of pathogens or targets, including antiviral prophylactics, antitoxins, and antivenins. These products can be applied throughout disease progression: pre-exposure, post exposure prophylaxis, early treatment to prevent severe symptoms, and even late treatment if severe symptoms develop.
Future Directions
A complication with using HIG therapy is the highly variable response to a pathogen that is possible in humans. Current exploratory projects are attempting to alleviate the need for human plasma by humanizing cows or pigs to yield antibodies similar to those produced in humans. Transgenic cattle have been engineered to develop HIGs against viral pathogens, including the Ebola virus, ZIKV, seasonal influenza virus, and SARS-CoV-2.
Modes of antibody administration can also be explored. Current routes include intravenous, intramuscular, and subcutaneous; however, nebulization and aerosol delivery are being investigated. This direct-to-lung administration could be especially beneficial for respiratory pathogens.
Ultimately, the administration of polyclonal antibodies through HIG therapy has many implications in medicine. Exploring this avenue of treatment can reduce the severity of symptoms that patients experience, as well as lower the mortality rate for some diseases. If polyclonal antibodies can be rapidly developed following the onset of a new pathogen or strain, future pandemic response times can be reduced, and the threats can be mitigated faster.
