Scratch the surface of almost any health issue that involves the immune system and uncertainty shows up. This includes the regrettably political issue of vaccines. Vaccination is one of the greatest public health innovations of all time. They are wildly effective compared to other medical interventions, have prevented many millions of deaths over time, and continue to prevent 2 to 3 million deaths worldwide on a yearly basis. And at the same time, there are elements of vaccination that are complicated and not fully understood.
In general, most vaccines look to educate B cells to fight a particular disease. B cells create immunity by generating antibodies–proteins that specifically bind to the surface of viruses. Once an antibody is docked onto the virus, it frustrates the ability of the virus to enter cells and replicate. Antibodies attached to viruses also act as flags that alert other immune cells to the presence of virus requiring elimination.
Often the body maintains copies of antibodies that have been useful in the past, so that if the virus returns, it can be recognized and countered more quickly. This phenomenon is known as immunological memory. Vaccination relies on this memory to tamp down the effects of viruses that are encountered again. That memory is short in terms of the flu for which vaccines are required every year (in part because influenza is variable); the memory is moderate in terms of mumps (every ten years); and long in terms of measles (lifelong).
Over the last two centuries we’ve moved from transfering the contents of a diseased pustule from the infected to the uninfected, to the use of viral DNA to educate the immune system of a threat. Despite the enormous progress made, questions remain. In the realm of infectious diseases, numerous studies have shown that vaccinating against a specific pathogen often provides immunity against other, unrelated pathogens as well. The surprising outcome has been given a notably ‘under the radar’ name: “non specific effects”. For example, when BCG is administered–a live vaccine meant to combat tuberculosis—it seems to dampen mortality rate from all causes (relative to the unvaccinated).
Non specific effects may arise when antibodies created for the vaccine act on viruses with proteins that are “similar enough” to the target protein. In this kind of cross reaction, vaccinating gives the patient two for the price of one–protection from the original virus, and other viruses that are similar in terms of their surface proteins. But it also seems to affect susceptibility to viruses that are unrelated to the target virus.
A relatively new explanation (2015) for non specific effects suggests the act of vaccination has implications for the first line immune cells, even though vaccines are engineered to speak directly to B and T cells (second line cells). Innate immune cells, the first to encounter and identify threats, have historically been described as cells that lack memory. An innate immune cell’s response to an invader does not change from one meeting to the next, or so the story went.
But findings in plants, insects, mice–and more recently, humans–suggest that innate immune cells can respond to a threat in a way that allows for a quicker response on repeat contact. It occurs as a consequence of epigenetic changes to innate cells and lasts for months rather than years. Uncovering a source of innate immune memory is a wild departure from the last hundred years of immune system understanding, and highlights the fact that work remains to understand the intricacy of the system.
These relatively recent findings will potentially be put to use for the current pandemic. Recently, some have suggested using vaccines for non-covid-19 viruses in an attempt to create non specific effects that may inhibit corona virus. There’s certainly no guarantee it will work…but perhaps it will buy us time until the more specifically targeted vaccine comes on line.