Thomas has started a series on vaccines and disease and I thought it was such a great idea that I would hijack it, kind of.
While Thomas talks about specific vaccines and their impact on certain diseases I thought I would cover some more general topics under the umbrella of vaccines. So let me present my own vaccine mini-series to supplement Thomas’ – Vaccines: how they are made?, how do they work?, and why we can’t rely on therapeutics alone in the fight against disease?
This week we will look at how some of the common ways vaccines are made. This has been a topic of interest to me for a while, ever since I heard someone from the (miss-information spreading, anti-vaccination supporting) Australian Vaccination Network giving a talk at a Vegan festival about the dangers of vaccines. In front of a room full of people this woman proudly proclaimed that the polio vaccine is made in monkey brains and if you let your child take the oral polio vaccine they will be eating monkey brain. I was dragged away before I could ‘politely question’ the woman by my wife, who had declared a science free weekend .
Anyway, the point is that this woman was talking crap. There would be no logic to making the vaccine in monkey brains, how many monkey brains does she think evil scientists can get their hands on? All the monkey heads I get my hands on are used in the construction of two headed monkey slaves. I wouldn’t waste them on vaccine production.¶
So what are the different types of vaccines and how are they made? There are a number of different types of vaccines and each have been developed for different reasons, to prevent different types of disease and to do specific jobs once inside the body. I’ll talk more about the body’s response next week but for now we can just look at the vaccines.
One of the oldest and most popular vaccines is the ‘killed vaccines’. As is implied the killed vaccines are whole infectious particles that are killed or inactivated in some way so they are no longer infectious but, importantly, still look to the immune system like they would if they were alive. Inactivation can be done using chemicals such as formalin and formaldehyde or can simply be ‘heat-inactivated’ or as I like to think of them – cooked. The early pneumococcal vaccines were cooked and now smallpox and Hepatitis B vaccines can be produced in this way. The inactivated vaccines are great because it is impossible for them to cause disease, they’re dead – so they’re fine.
A variation of the inactivated vaccines are the toxoid vaccines. These vaccines are designed to protect not against the whole micro-organism but against any toxic product it may make. Generally this involves taking the toxin itself and heating it. This works particularly well for protein toxins as they unravel when heated excessively so the protein toxins are rendered useless but even unravelled all the toxin components remain present allowing your immune system to recognise the constituent parts and, with any luck, the normal form of the toxin as well. Tetanus and diphtheria toxins have been used to make toxoid vaccines but snake and spider venom have also been used and are administered to farm animals in some cases.
Attenuated vaccines are a little different because they involve a live infectious disease particle that has been severely weakened. They are often more effective than inactivated vaccines because you can generally introduce the attenuated version via the normal route of infection to maximise the appropriate response. To attenuate an infectious organism the best and most utilised way is to take a human version of the disease and force it to infect something not human. That could be a whole animal like a mouse or a cell line derived from another spices such as Vero cells that were derived from monkey kidneys. If you force the infection and collect the micro-organisms that were successful and re-infect your non-human host number of times (generally 7-8 times) you can end up with a human pathogen that is optimised for infecting a non-human. This gives you immune system a significant advantage in generating an immune response and life-long protection against something that looks like the real thing but doesn’t behave like the real thing.
In some cases using the using the entire infectious agent can be less effective than using only the parts that will be the target of the immune response. Subunit vaccines are generally produced for viruses and are enormously useful as vaccines. Just as the name suggests rather than using a whole dead virus or a weakened version of a live virus the sub-unit vaccines just use a part of them and often that part is the component that will interact with the immune system under normal conditions. When a virus infects a cell it does so to manufacture more copies of itself and its genome. Following manufacture of all the viral elements they must be assembled into new viruses but this is a random and often inefficient process. Often genomes are left out of assembling virus particles leaving an empty shell. This shell can leave the cell and infect a new cell but doesn’t contain a genome so cannot deliver a payload of viral DNA. Researchers noticed this and found that if you could prevent genome entry you could produce virus-like particles that contained all the bits of the virus except for the genome, therefore could be seen by the host’s immune system but were entirely non-infectious! HepB, Human papilloma virus and some flu vaccines are made like this. These vaccine types are effective but as they do not persist in the host often require multiple doses for full activity.
Finally the last major group of vaccines are the conjugate vaccines. Conjugate vaccines contain something you want the immune system to target conjugated or ‘stuck’ to something the immune system will easily recognise. The most obvious example (to me anyway) are the current Pneumococcal vaccines. The outer coat of the bacteria is made of sugars that the immune system doesn’t recognise easily but when stuck to a an inactivated form of the diphtheria toxin the immune system can recognise both and protection against the sugar is maintained.
The vast majority of vaccines these days are made as subunits or conjugates as we move away from giving people whole bacteria or viruses. This is due to cases of re-activation or incomplete killing of vaccine stocks resulting in the very disease the vaccine was designed to protect against. Even still given the amount of vaccinations that occur each year and the proportionally tiny number of adverse reactions it’s easy to see vaccines for the wonderful addition to preventative healthcare that they are.
¶ Whilst I maintain the woman was wrong there is a connection between monkey brains and polio vaccines and just the faint hint at truth is all that’s needed by the anti-vaccination groups.
In the early 1930’s polio virus was harvested from monkey spinal cords by grinding them up and treating the pulp with formaldehyde which inactivates the virus. After testing the mixture on himself and others in his lab, Maurice Brodie trialled it on a sample of 3000 children. It didn’t work, at all. Not a single person developed immunity to polio and some suffered adverse reactions to the mixture, resulting in it never being used again. That’s it, that’s the polio – monkey brains link.
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