The most recent 20 comments posted to Making Light by iayork:

albatross@201:
[1] If I understand correctly, the genetic diversity in MHC/HLA mainly affects the adaptive immune response. (Is there some diversity in PRRs or something, too?) I think that means that this kind of diversity should have less impact on whether you catch the flu than on how well your body deals with it.

You're correct in the MHC variation -- mainly adaptive responses. There are variations in PRRs but the clinical relevance of this isn't clear except for the really blatant cases where some receptors are missing completely. Some of the large-scale genome scans have turns up allelic variants in some of the PRRs as links with risks of some diseases, but the differences are not huge. I'm not aware of any genomic scans for flu susceptibility (though it would be very interesting -- but I'm not aware of any evidence for genetic variation in flu susceptibility at all, though I'd bet there is some.)

I wonder how different, genetically, central American Indians from whom most Mexicans are partly descended are from North American Indians and South American Indians. My impression here is that all the Indians wound up with a lot less diversity in their MHC/HLA genes, presumably because of some combination of a small founding population and not having had anything like the same level of constant exposure to nasty pathogens, century by century. But it would be interesting to see some details on this....

Native Americans have reasonable MHC diversity (see for example the map in http://www.iayork.com/MysteryRays/2007/10/09/ ). The region diversifies incredibly rapidly (for an example see http://www.iayork.com/MysteryRays/2007/09/20/ .

I think it's extremely unlikely (though nothing's impossible) that there's any kind of significant genetic difference underlying the apparent differences in mortality rates; I am fairly confident that it's a case of the missing denominator -- the Mexican authorities mainly tested seriously ill hospitalized patients, so it's not surprising that a larger proportion died -- they didn't test the general population, which was how the original US cases were identified. I strongly suspect that the virus is much, much more widespread in Mexico than the authorities were aware, and so the mortality rate is much, much lower than it seems.

But we won't know for a while.

Quick notes -
Even if I stipulate that flu bugs ARE mutating faster and with more change within strains, I'm not convinced that it's driven by having a larger population of vaccinated individuals.

I'm not aware of any evidence influenza viruses is mutating faster. Antigenic shift and drift have been going on for a long time and there have been several instances of massive change long before vaccination -- the 1918 flu was one such example of sudden major mutation. We are monitoring flu much closer now, obviously, and detecting far more changes for that reason.

That's not to say it's impossible for vaccine to drive changes in a pathogen population. Empirically it's surprisingly rare, but it does happen. There was a case of a variant pertussis bacterium that probably arose by escaping vaccine control (but that bacterium was less fit because of hte mutation, and as far as I know hasn't persisted). There's a better-studied, but still not definitive, case of vaccine-driven increased virulence -- Marek's Disease of chickens; I talked about it here.

One of the problems with an HIV vaccine is the probability that the virus population will quickly evolve away from vaccine control.

But aside from those cases, I don't know of any cases where it's actually happened. That's even with viruses that are highly unstable and mutate very rapidly, like poliovirus, for which vaccines have been highly successful.

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