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Why does drug resistance easily evolve but vaccine resistance does not?

rspb.royalsocietypublishing.org

21–30 of 42 posts

Re: Why does drug resistance easily evolve but vaccine resistance does not?

#21
post #17

Very good question and a very good answers in this article! I'll add one more reason not explored by the authors: antibodies don't "leak" in the environment, in contrast to the antibiotics which are everywhere. For example, if I'm vaccinated against S. pneumoniae (one of the bacteria that can cause pneumonia), the bacteria have to get inside my body to gain exposure to my vaccine-induced antibodies. This makes the em…

You don't excrete antibodies? I think you might be saying that antibiotics are passive strategies which are inherently overly broad and thus problematic.

Antibodies are too large to pass through the filter in the kidneys. Lower molecular weight fragments of antibodies are usually reabsorbed in the proximal tubule of the nephron.

Their fate mostly lies in catabolism, i.e. they are broken down and the components reused. Biliary excretion accounts for a very small amount of the elimination of IgG antibodies.

[0] "Pharmacokinetics of Monoclonal Antibodies" http://onlinelibrary.wiley.com/doi/10.1002/psp4.12224/pdf

Re: Why does drug resistance easily evolve but vaccine resistance does not?

#22

Earlier quoted context omitted.

You don't excrete antibodies? I think you might be saying that antibiotics are passive strategies which are inherently overly broad and thus problematic.

Antibodies are too large to pass through the filter in the kidneys. Lower molecular weight fragments of antibodies are usually reabsorbed in the proximal tubule of the nephron. Their fate mostly lies in catabolism, i.e. they are broken down and the components reused. Biliary excretion accounts for a very small amount of the elimination of IgG antibodies. [0] "Pharmacokinetics of Monoclonal Antibodies" http://onlineli…

Shouldn't I be able to edit this for a little while? Strange, only two minutes later and I can't edit. It had no replies.

I tried adding this quote from the linked paper:

> Thus, IgG elimination occurs mostly through intracellular catabolism by lysosomal degradation to amino acids after uptake by either pinocytosis, an unspecific fluid phase endocytosis, or by a receptor-mediated endocytosis process.

Explanation of two words in there that maybe not everybody knows:

pinocytosis: The ingestion of liquid into a cell by the budding of small vesicles from the cell membrane.

endocytosis: The taking in of matter by a living cell by invagination of its membrane to form a vacuole.

EDIT: I can still edit this comment more than five minutes later, as expected. Hmm... why could I not do that with my first comment...?

Re: Why does drug resistance easily evolve but vaccine resistance does not?

#23
post #17

Very good question and a very good answers in this article! I'll add one more reason not explored by the authors: antibodies don't "leak" in the environment, in contrast to the antibiotics which are everywhere. For example, if I'm vaccinated against S. pneumoniae (one of the bacteria that can cause pneumonia), the bacteria have to get inside my body to gain exposure to my vaccine-induced antibodies. This makes the em…

You don't excrete antibodies? I think you might be saying that antibiotics are passive strategies which are inherently overly broad and thus problematic.

As pointed out by IIIIIIIIIIIIIII, antibodies are way too massive and are not excreted in any significant amount (again, I am talking of normal physiology, not someone with very advanced kidney disease).

To give you an idea of the weight difference, an average human IgG[1] antibody is about 500 more massive than a pretty average small molecule antibiotic like levofloxacin[2]

[1]: https://en.wikipedia.org/wiki/Immunoglobulin_G

[2]: https://en.wikipedia.org/wiki/Levofloxacin

Re: Why does drug resistance easily evolve but vaccine resistance does not?

#24
post #17

Very good question and a very good answers in this article! I'll add one more reason not explored by the authors: antibodies don't "leak" in the environment, in contrast to the antibiotics which are everywhere. For example, if I'm vaccinated against S. pneumoniae (one of the bacteria that can cause pneumonia), the bacteria have to get inside my body to gain exposure to my vaccine-induced antibodies. This makes the em…

They actually do adress this, in what i thought was the weakest part of the paper, the "non-key factors" section.

Fourth, vaccines are only active while pathogens are inside hosts, but drugs can remain active in environmental reservoirs [89], suggesting that the strength of selection for resistance may differ for drug and vaccine resistance. However, drug resistance readily evolves even in pathogens that lack environmental life stages such as HIV [8].

Re: Why does drug resistance easily evolve but vaccine resistance does not?

#25

Earlier quoted context omitted.

Antibodies are too large to pass through the filter in the kidneys. Lower molecular weight fragments of antibodies are usually reabsorbed in the proximal tubule of the nephron. Their fate mostly lies in catabolism, i.e. they are broken down and the components reused. Biliary excretion accounts for a very small amount of the elimination of IgG antibodies. [0] "Pharmacokinetics of Monoclonal Antibodies" http://onlineli…

Shouldn't I be able to edit this for a little while? Strange, only two minutes later and I can't edit. It had no replies. I tried adding this quote from the linked paper: > Thus, IgG elimination occurs mostly through intracellular catabolism by lysosomal degradation to amino acids after uptake by either pinocytosis , an unspecific fluid phase endocytosis , or by a receptor-mediated endocytosis process. Explanation of…

If this was your literal first comment, it could be some form of SPAM or trolling protection

Re: Why does drug resistance easily evolve but vaccine resistance does not?

#26
I like to use a conflict analogy: A drug is a weapon exploiting one weakness of the enemy. A vaccine is a visual identification of the enemy, passed on to special forces (your immune system). A single weakness can often be changed easily, but it's harder to shake off special forces.

Re: Why does drug resistance easily evolve but vaccine resistance does not?

#27

Earlier quoted context omitted.

Shouldn't I be able to edit this for a little while? Strange, only two minutes later and I can't edit. It had no replies. I tried adding this quote from the linked paper: > Thus, IgG elimination occurs mostly through intracellular catabolism by lysosomal degradation to amino acids after uptake by either pinocytosis , an unspecific fluid phase endocytosis , or by a receptor-mediated endocytosis process. Explanation of…

If this was your literal first comment, it could be some form of SPAM or trolling protection

It was the 2nd comment, and since it's not been very long since the first one I remember that I edited it quite extensively, many times, for well over five minutes. This time I could start editing but could not (successfully) submit the edited text just two minutes after posting the comment, according to the time printed just above my comment after I submitted the edit (which only showed the text before the edit, and the "Edit" link was now gone).

Re: Why does drug resistance easily evolve but vaccine resistance does not?

#29
post #17

Very good question and a very good answers in this article! I'll add one more reason not explored by the authors: antibodies don't "leak" in the environment, in contrast to the antibiotics which are everywhere. For example, if I'm vaccinated against S. pneumoniae (one of the bacteria that can cause pneumonia), the bacteria have to get inside my body to gain exposure to my vaccine-induced antibodies. This makes the em…

Antibodies stay in the body.

Re: Why does drug resistance easily evolve but vaccine resistance does not?

#30

Don't bacteria have a way of swapping genes that was discovered recently?

If by "recently" you mean 1946, then yeah: https://en.wikipedia.org/wiki/Bacterial_conjugation

Unless you mean across species, in which case there are new and interesting ways that bacteria can swap genetic elements across species boundaries being discovered all the time. The first example was the original Griffith experiment in 1928, but the wiki article here: https://en.wikipedia.org/wiki/Natural_competence has a nice timeline of some of the more recent examples as well.

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