'Not responding well to vaccines'-- It is in your genes (well, partially)

Sometimes, people do not respond well to vaccines.

What I mean by that, is that sometimes a person will not generate a protective immune response to a particular vaccine on a given day... the whole point of vaccination.

Now that person might respond (and have responded) just fine to other vaccines. Or they might respond to that exact same vaccine just fine on another day. Or they might get that same vaccine several times, and never generate a protective response.

We do not know why this happens, thus we cannot predict who will or will not respond well. And then we dont know who responded well until the non-responders get sick. Thus you, me, we could be 'non-responders' to measles, and we wont know it until we get sick because some jerk decided not to vaccinate their kids, and then let their measles infested children attend a concert we all attend.

Happily, not responding to a vaccine is infrequent. If everyone was vaccinated, the rates of 'not responding' are still low enough that they, and everyone else, should be protected via herd immunity.

BUT, if we understood why this phenomenon happens, we could figure out ways around it to make sure everyone who gets a vaccine reaps its benefits, and we know it.

We do know the bare bones of what is going on--

Some non-response is due to chance, thanks to the randomness inherent in our immune system.

Some of it has to do with environment-- maybe the non-responders allergies were really acting up that day, or maybe they thought they were over a recent cold more than they actually were, and that interfered with the vaccines efficacy.

And some if it might have to do with our genetics. Somehow. Somewhere. We dont really know outside of obvious things like MHC type :-/

We just gained a bit more insight into why some people do not respond well to the measles vaccine:

CD46 measles receptor polymorphisms influence receptor protein expression and primary measles vaccine responses in naive Australian children.

Measles needs a protein on the surface of your cells in order to successfully mediate infection: CD46

There are some differences between individuals CD46 gene, thus differences in CD46 protein shape and function.

To stop measles from infecting a cell, you need to stop the interaction between measles and CD46. Usually that is mediated by neutralizing antibodies-- antibodies stick to the virus and prevent its virusy arms from grabbing onto the cell it wants to infect.

But if not all CD46 proteins are equal, then preventing the measles-CD46 interaction might be an easy... or a difficult... task. Maybe stopping the interaction is difficult because of high affinity between a particular CD46 variant and measles. Maybe it is more difficult because a particular CD46 variant is transcribed or translated or processed faster, thus there is a lot more of it available on the cell surface for measles to find. We dont know.

These scientists looked at kids who had just gotten the measles vaccine, and compared the CD46 genes of the responders and the non-responders. The children who had mutations at the right spot, in a particular flavor, seemed to respond better than others. But if a child had a mutation at the right spot, but not a mutation of the right flavor, they didnt respond as well.

Now, there were not many children in this group, and the participants were white (limiting the genetic diversity sampled), but it is pretty neat to have this kind of information! So, all of you folks out there with a 'GG' at location rs2724384, stay away from people with measles! You might not be protected!!


Which highlights the fact that this research has "unclear clinical relevance at this stage". Those words are straight from the author. Its not me being a Debbie Downer this time!

Lets say the experimental group was HUGE and there was a clear-cut connection between your genetics and how you respond to a vaccine. What are we supposed to do with that information? There is nothing we can do about it.


All we can do is keep investigating not only the differences, but the clear how/why of the differences, so we might be able to figure out how to turn a non-responder into a responder. So this isnt super useful information YET... but it will be one day!

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There are some differences between individuals CD46 gene, thus differences in CD46 protein shape and function.

Are there differences great enough to prevent measles from binding in the first place?

Soon enough, doctors will be able to know in advance if you would be allergic to a vaccine, or offer different vaccine formules adapted to the peculiarities of your immune system.


Clearly, Abbie, the non-responders are just a trick played Satan to fool scientists. What? You think he only spends his time hiding fossils?

This is interesting.

I only read the abstract (because that seems to be all I have access to), but that was enough for me to note that the very appropriate measure of vaccine effectiveness that they used was anti-measles IgG titer.

In other words, if you have the "wrong" CD46, you get the vaccine, but you don't make a decent amount of antibody.

I can think of two logical possibilities (not to imply that there are only two; these are just the two I can think of) -

1) Some variants of CD46 might literally bind the antigens in the vaccine with high affinity in some way that essentially removes the necessary antigens from the view of the immune system before a response can be generated.

2) Some variants of CD46 might interact with the immune system to prevent or dampen a response to CD46-binding antigens.

The assumption in this paper, and it's a solid assumption, is that if the vaccine produces an adequate antibody response, it's overwhelmingly likely that, barring future severe immunosuppression, the patient is protected.

And then we dont know who responded well until the non-responders get sick

In fact, you can check your antibody titers. The incremental cost to society of doing this is extremely low. Labs probably charge a lot, which is a different issue.

Does having a strong anti-measles IgG response absolutely guarantee that you are immune to measles? Not necessarily, under every possible circumstances, but if you are otherwise healthy (and indeed, even in most cases where you aren't), it's overwhelmingly likely that if you've got the antibodies, you're immune.

Are there differences great enough to prevent measles from binding in the first place?

Technically not stated. But this should not necessarily prevent an antibody response. Measles infects the cell via CD46, but the immune mechanism will mainly be mediated by unique T cell and B cell receptors (the former are similar to antibodies and the latter are membrane bound antibodies) that recognize a measles antigen. Measles gets in via CD46, but other measles-binding proteins set off the immune response.

I'm guessing that they must not have any reason to think that this population has a lot of people innately resistant to measles in it, but technically that isn't stated.

I don't understand how the inexperience of children can effect the measles vaccine response, but I must admit I don't follow a lot of things you write.

It's a little more complex than this: it's only the seriously attenuated measles vaccine that uses CD46 molecules as receptors, not the normal virus. Wild measles uses a protein called SLAM and one called nectin-4.

The interesting this is that CD46 is expressed in basically every cell in the human body while SLAM and nectin-4 are only expressed in a minority of cell types (immune cells and epithelial cells respectively). The theory in this paper is that the infectiousness of the vaccine strain of measles is changed because of these CD46 polymorphisms.

This is a live, replicating vaccine virus so I guess you must need at least some replication and growth in your body following the immunisation jab. What would be nice is to do some experimental work relating CD46 genetic differences with measles growth in an animal. This group have also looked for associations between the wild measles receptors and antibody response, no surprise there wasn't much of one.

I don't understand how the inexperience of children can effect the measles vaccine response, but I must admit I don't follow a lot of things you write.

Assuming you're not being sarcastic - naive in this context means "has never before been exposed to measles virus or the measles vaccine", ie their immune system is what's inexperienced. If some of the children *had* seen measles/measles virus before, you would get (you hope) very strong responses, stronger than after initial exposure, because their B cells would be like "HEY! I've seen this mother****er before! GET IT!!!", whereas a measles/vaccine naive child's immune system is all "huh? What's this? Noo, do no want, must do something about this..."

Thanks, harold.

fnxtr -

You are welcome. See also Connor Bamford's comment. It does not really change anything I said, but it clarifies that only the attenuated vaccine strain of measles uses CD46 as a receptor (the paper was about response to the vaccine). Which makes it vanishingly unlikely that the variant alleles for CD46 investigated here would confer innate resistance to measles.

To summarize, when the vaccine works, it provokes an immune response, including an antibody response, which makes the vaccine recipient immune to "normal" measles as well as to the attenuated strain used in the vaccine.

For some reason, people with certain variant alleles of the gene for CD46 don't respond to this vaccine by generating an antibody response (the only response that was measured, which is perfectly reasonable by the way, if I read the abstract correctly).

Herd immunity myth:

According to this article, "The herd immunity theory was originally coined in 1933 by a researcher called Hedrich. He had been studying measles patterns in the US between 1900-1931 (years before any vaccine was ever invented for measles) and he observed that epidemics of the illness only occurred when less than 68% of children had developed a natural immunity to it. This was based upon the principle that children build their own immunity after suffering with or being exposed to the disease. So the herd immunity theory was, in fact, about natural disease processes and nothing to do with vaccination. If 68% of the population were allowed to build their own natural defences, there would be no raging epidemic.
Later on, vaccinologists adopted the phrase and increased the figure from 68% to 95% with no scientific justification as to why, and then stated that there had to be 95% vaccine coverage to achieve immunity. Essentially, they took Hedrichâs study and manipulated it to promote their vaccination programmes."

(MONTHLY ESTIMATES OF THE CHILD POPULATION "SUSCEPTIBLE' TO MEASLES, 1900-1931, BALTIMORE, MD, AW HEDRICH, American Journal of Epidemiology, May 1933 - Oxford University Press).

Source: http://www.vaccineriskawareness.com

he observed that epidemics of the illness only occurred when less than 68% of children had developed a natural immunity to it

is not the same as

If 68% of the population were allowed to build their own natural defences, there would be no raging epidemic.

Aside from the obvious idiocy of the claim that we have to allow epidemics to occur to stop epidemics from occuring, there is a major change in definition that completely invalidates the argument. Children make up roughly 1/7th of the population. Prior to vaccination, virtually all adults acquired their own natural defense (via epidemics of measles, naturally). That means that at any given time, about 84% of the population are immune by virtue of having lived long enough. Of the remaining 14%, 68% need to be immune to temporarily stop epidemics from occuring. That's an additional 10% of the population. Therefor, Hedrich observation that 68% of children being immune prevents epidemics is equivalent to 94% of the total population being immune. 95% is awfully close to that 95% mark quoted above, isn't it?