Updated: Feb 8
The Next Generation of Pandemic Response
By Ravi Starzl
Immunization is a process of fortifying an individual’s immune system against an agent, typically disease-causing pathogen or a toxin. When the immune system is exposed to foreign molecules, this will trigger an immune response. Because of immunological memory, our immune system is also able to develop the ability to respond quickly to any subsequent encounter with the same agent, which is a function of the adaptive immune system – a subsystem which responds within 4-7 days to a previously encountered foreign molecule. The concept of exposing the body to a foreign agent in a controlled manner to artificially activate the immune system and impart the ability of a quick response to a subsequent encounter due to immunological memory is called active immunization.
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Active immunization gives the body the ability to produce antibodies to counter the pathogen or a toxin on its own. The most common technique of active immunization is vaccination, a process of introducing a microorganism or a virus in a weakened, live or killed state, or proteins or toxins from that microorganism, triggering the body’s adaptive immunity. This allows the body to quickly respond to a next encounter with the same pathogen or toxin. Inoculation refers to a method where the body is exposed to a milder form of a disease to induce immunity. It originated as a method of preventing smallpox, where dried smallpox macules were used to induce a generally milder form of the disease, which still induced full immunity to the disease. Compared to vaccination, it is inferior due to significantly higher risk – vaccination does not cause disease, even in its milder form, while inoculation does.
Passive immunization is a process of introducing antibodies into the body directly, rather than imparting on the body the ability to produce them. This still imparts immunity, however, because this immunity is not caused by the body’s immune system, it will only last as long as the introduced antibodies as present in the organism. This is called transient immunity. Antibodies have been used for the prevention and treatment of various diseases for centuries (Keller, 2000). Immunization by the administration of antibodies is a very efficient way of obtaining immediate, short-lived protection against infection or the disease-causing effects of toxins from microbial pathogens or other sources.
Due to its rapid action, passive immunization is often used to treat diseases caused by infection or toxin exposure. In bacterial diseases, antibodies neutralize toxins, facilitate opsonization, and, with complement, promote bacteriolysis. In viral diseases, antibodies block viral entry into uninfected cells, promote antibody-directed cell-mediated cytotoxicity by natural killer cells, and neutralize virus alone or with the participation of a complement. Prior to the discovery of antibiotics, antibodies were the only available treatment for a significant number of infectious diseases. They can be administered as:
human or animal plasma or serum
pooled human immunoglobulin for intravenous (IVIG) or intramuscular (IG) use
high-titer human IVIG or IG from immunized or convalescing donors
monoclonal antibodies (MAb).
Passive immunization occurs widely in nature to protect offspring against disease at birth and during lactation in mammals, through the transfer of immunoglobulins from mother to its offspring. This can be dated back hundreds of millions of years, to the primitive species of fish. In humans, the half-life of immunoglobulins (IgG) is about 3 weeks, making the maternal antibodies active in children 2-3 months old (Shahid, 2002). In birds (IgY) and fish (IgM), immunoglobulins have a shorter half-life of only a few days (Hedegaard, 2016). Passive immunization is not a real alternative to vaccination, as it does not confer long-term immunity. However, vaccines are not a viable option for immuno-compromised people, whose immune system is too weak to respond to an infection with its antibodies. Passive immunization provides immunity regardless of the body’s own response to infection, making it a viable option for these cases, too.
Due to the long-lasting immunization effects, vaccination is considered the superior method of imparting immunity. There are currently 27 diseases for which vaccines are available (World Health Organization, 2011). However, vaccination is only available for known diseases or known strains of viruses, and developing a new vaccine is a long and expensive process (Struck, 1996). As a consequence, many infectious diseases that have emerged over the past few decades have seen little or no vaccine development, due to a relatively small number of infections and perceived lack of commercial market for such products (Hixenbaugh, 2020). Long development and testing processes make vaccines eminently unsuitable as a rapid response tool for emerging diseases.
Even when a disease represents a mutated form of a known pathogen, there is no guarantee that the vaccine for the original pathogen would be fully effective, and in most cases, it is not (like with different influenza strains). This is particularly pertinent in today’s globalized world, where epidemics have a greater potential to spread worldwide than ever before. Therefore, while vaccines represent our best defense against infectious diseases, there is still a need for a “firebreak” – a set of measures designed to delay the spread of a disease long enough to allow for vaccine development. This report is meant to offer an introduction to the concept and strategy of passive immunity as a mechanism of rapid pandemic response and a broad overview of the current state of technology.