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Activity 2: An introduction to vaccines History and success Vaccination has been developed as a very powerful method for protecting people against infection by pathogens. It has been integral in controlling some of the most dangerous pathogens in the world (e.g. Smallpox, Polio, Diphtheria, Rabies). Follow this link if you want to learn more about how vaccination was used to eradicate smallpox: http://www.bbc.co.uk/history/british/empire_seapower/smallpox_01.shtml How does vaccination work? Vaccination works by mimicking a real infection, allowing the immune system to encounter the pathogen in a safe way and produce the relevant antibodies so that it is ready to respond quickly should it encounter the pathogen again. This state of preparedness is known as immunity. The first step of vaccination is to introduce a weakened or dead pathogen, which can’t cause any damage, into the body to be presented to the immune system. Some B cell antibodies will recognize antigens on the pathogen, become activated and then multiply, producing copies of themselves. Some will develop into memory B cells which are long-lived and constantly patrol the body ready to respond quickly by producing lots of antibodies if the pathogen is ever encountered again. This means that if the real pathogen ever infects the vaccinated person it will have very little time to infect cells before it is recognised and attacked by the specific immune system. (Image adapted from http://cnx.org/) This graph illustrates the speed and strength of the immune response (measured by concentration of antibodies in the blood) after an initial and secondary exposure to a pathogen. Can you explain what is shown by the graph? Imagine two scenarios: one where the first exposure is a real infection and one where the first exposure is a vaccine and the second exposure is real. What are the major differences between the antibody responses to the real exposures? What effect do you think this would have on the level of damage caused by the pathogen? Types of vaccine We have learnt that vaccines work by presenting a foreign antigen to the immune system to evoke an immune response, but there are several ways to do this. There are four main types of vaccine which are currently in clinical use: 1. Inactivated vaccines are created by growing a virus or bacteria and then killing it using heat or formaldehyde. This prevents the pathogen from causing disease but keeps it intact enough to be recognized and remembered by the immune system. These vaccines are simple and quite cheap to make but as the pathogen is dead and cannot replicate the immune response is not very strong and so often multiple ‘booster’ vaccinations are required. Although extremely rare, there have been occasions in the past when the pathogen was not fully killed resulting in people being vaccinated with infectious material e.g Poliovirus in the ‘Cutter Incident’. Those interested can read more here: http://en.wikipedia.org/wiki/Cutter_Laboratories 2. In attenuated vaccines, live pathogen is used but is weakened by growing it in the cells of other species so that they are not well adapted to infecting humans. They are still able to replicate, but do so very slowly. Replication allows the pathogen to present antigen to the immune system for a time following vaccination. There is always a risk of the pathogen reverting back and causing disease although this is very low. 3. Subunit vaccines present an antigen to the immune system without introducing the complete viral particle. This method is very safe however does have some drawbacks. One weakness is that the antigen alone can have a different threedimensional structure compared to when it is part of the complete virus and will induce antibodies that may not recognize the complete, infectious virus. It is in part because of this that subunit vaccines often elicit weaker antibody responses than the other type of vaccine. 4. Virus-like particle (VLP) vaccines are made using the one or more viral proteins that make up the outer shell of a virus (this is the main part that the immune system recognizes and interacts with). These proteins can assemble into particles that resemble the virus from which they were derived but lack viral genetic material. They are safer than inactivated and attenuated vaccines because the virus is incomplete and therefore cannot replicate. As the entire outer shell of the virus is used, VLPs also typically elicit a stronger immune response than subunit vaccines. Explore the website below, these two links in particular will give you more insight into how vaccines work: http://www.historyofvaccines.org/content/how-vaccines-work http://www.historyofvaccines.org/content/types-vaccines Visit the HE+ forum to discuss the history of vaccines.