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I understand there are two kinds of active vaccination

  1. Injecting complete viruses that are weakened to not cause the disease being vaccinated against

  2. Injecting only antigen particles of viruses that the body creates antibodies for. So the disease can't arise, not even in a weakened form.

I am wondering how the viruses for vaccination are weakened. Is this simply a process where randomly parts of the virus DNA/RNA are taken out and tested on animals, and as soon as it is sufficiently weakened, it is considered suitable? Or is this an analytical and systematic process?

I am wondering because some popular vaccinations (including that against measles) can still (very rarely) cause fatal complications. Which made me think whether it's systematic or just "accelerated mutation and selection".

I'm interested in an answer for layman, if that is possible at all.

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2 Answers 2

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There is a Wikipedia page on the topic of attenuated vaccines.

Basically the idea is that the virus is grown on some sort of foreign host such as cells in culture, eggs or an animal. This selects for mutant viruses, present in the original population, which are pre-adapted to the new host (so that they grow better). By repeating this process several times it is possible to develop a new variant of the virus which grows poorly in the original host (i.e. humans) but is still able to stimulate an immune response. The resulting antibodies, will recognise a subsequent infection by the original disease-causing virus as long as the viral component responsible for the immune response is still present in the attenuated virus that is used for vaccination.

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  • $\begingroup$ So simply the fact that the virus now replicates in a foreign host is enough to ensure that it no longer affects humans? I would have expected that there needs to be some sort of selection for strands which do not make humans sick, but obviously the only way to do that would be to try the mutation on humans which is not possible for ethical reasons. $\endgroup$
    – gTcV
    May 23, 2020 at 5:50
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There are basically three classical possibilies:

  • Using an attenuated virus as Alan described in his answer
  • use only parts of viruses (here mostly proteins, which are displayed on the surface of the virus and which can be recognized by the immune system)
  • inactivated viruses (here often formaldehyde is used, which changes parts of the proteins, the formaldehyde is then cleaned away to have the vaccine free of it)

The part you describe about using DNA from a virus is done these days. It is called "reverse vaccinology" and uses conservation analysis between different strains (this is also used for bacteria) to get a vaccine which covers as much different strains as possible. For the vaccine, proteins are selected which are conserved as good as possible and which show no similarities to human proteins (you don't want to induce autoimmunity). Candidate proteins for a vaccine are then expressed biotechnically and tested if they work.

Complications in vaccinations (which are really rare, for measles the chance for complications is 3-4 orders of magnitude lower than when actually get the disease) are usually due to allergic reactions.

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