Basis for Efficacy and Failure of Vaccines
Dr. Melissa Mazan
It seems so simple. Just give your horse a few jabs every spring and you've taken care of all those nasty diseases – tetanus, influenza, Potomac Horse Fever, strangles. Is it really so simple? No, is the resounding answer. Vaccination is a complex and tricky business. In essence, we are trying to fool Mother Nature – and that can be a difficult thing to do indeed. We're trying to convince the horse's immune system that it has already seen and successfully fought off a disease without ever becoming sick.
The Immune System Made Simple
There are two major parts of the immune system: the humoral, or blood borne portion, and the cellular portion. Both of these portions of the immune system rely on being able to distinguish between self and non-self, or foreign. Both the humoral and the cellular system do this by recognizing portions of foreign molecules (termed antigens). Most people have heard of antibodies – these are the keystone of the humoral immune system, which is most effective against bacteria. The antibody is a molecule that recognizes a unique part of the pathogen, and effectively docks with the pathogen. Once this portion of the virus or bacteria is covered with antibody, other parts of the immune system – such as inflammatory cells – can now recognize the invader as being foreign, and rush in to kill it. The cellular immune system also recognizes specific antigens, but it is most important for defense against invaders such as fungi, protozoa and viruses.
Both parts of the immune system rely on a process termed anamnesis, or memory. The first time that the immune system is called upon to make antibodies against bacteria A, for instance, it takes a while to get production going. The second, and perhaps third time that the immune system must make those antibodies, the production line is ready – and the response occurs very quickly. This is termed the anamnestic response. This is why most vaccines must given more than once in order for the animal to be properly vaccinated.
There are two major requirements for an effective vaccine. Remember that we are trying to prompt the specific arm of the immune system to get "geared up" for an attack by specific pathogens at some unknown time in the future. First, and foremost, the immune system needs to recognize the vaccine as being foreign – not self. Secondly, the vaccine must not actually cause disease. The very first vaccines were rather crude – a doctor recognized that milkmaids from the country tended to have beautiful complexions, because they tended not to get smallpox – a disease that either disfigured or killed its victims. He cleverly deduced that it was because the milkmaids were exposed to cowpox – which had much less virulent effects on people. The cowpox caused their immune systems to respond with an antibody that recognized not just cowpox, but also smallpox.
The biggest distinction among vaccines is killed versus modified live, or attenuated. The first smallpox vaccine was, in a way, a modified live vaccine – it needed to replicate in the body to elicit a strong immune response, but it was able to do that without causing disease. Today, live vaccines are still produced by weakening the pathogen in some way, while still allowing it to replicate in the host's body. Killed vaccines are exactly as they sound – no portion of the pathogen is alive and able to cause disease. Rather, the dead pathogen, or portions of it, are able to elicit an immune response merely by their presence. They are usually combined with an adjuvant – a molecule that non-specifically helps the immune system to respond to the vaccination.