Currently, in case you have not heard, there exists a novel flu virus called H1N1. The United States has produced a vaccine made from hemaglutinin proteins and does not contain adjuvants. Adjuvants are additives added into a vaccine misture to promote a stronger immunity.
There is currently little understanding of how adjuvants work, but it is hypothesized that they work by invoking a stronger immune response. Currently, the U.S. does not include it into the vaccines due to the FDA. However, many European countries are already using it.
So basically the breakdown is that the addition of adjuvants can conserve the limited supply of H1N1 vaccines by being able to use less vaccine material in order to produce the same immunity.
There does exist problems with adjuvants as a whole, in about 1-5 in 100,000 people, adjuvants can produce a autoimmune response and can result in RA, Guillaine-Barre paralysis, etc.
The question remains, should adjuvants be added into vaccines? Currently there are about 34 million vaccine shots available, and about 129 million people that need to be immunized (these numbers are variable depending on sources and risk groups), with the addition of adjuvants, it is theorized that it can double to quadruple the total supply of vaccine shots.
It’s not so much that an adjuvant makes immunity “stronger”. In many cases, it makes the immune response work at all.
If I just inject you with a protein that your body has never seen before in no adjuvant context, your immune system very well might either ignore it (immune ignorance) or the immune system will see that this protein is harmless and will actually be tolerized (immune tolerance) against the antigen in the future.
Adjuvant is generally just an additive that gives the vaccine context for the immune system. Contrary to what was taught in college biology courses, it’s become increasingly clear in recent years that the immune system doesn’t so much recognize “self” from “nonself” as it does “dangerous” versus “non dangerous”. If a “self” antigen is presented in the context of a “danger” signal (which could be something like bacterial cell walls, or uric acid crystals) then the immune system is actually able to respond. The dendritic cell (which does all of the antigen presentation in naive settings), without the context of the adjuvant has no known mechanism for recognizing a protein as being foreign, only mechanisms for recognizing danger, like their toll like receptors (TLRs). Only T cells have the specificity necessary to recognize self from nonself, but they require antigen presentation from the dendritic cell first. So, adjuvant is just a little bit of danger to activate the dendritic cell and give the vaccine a dangerous context.
My PhD is in immunology. I’m finally useful. And, I recognize I didn’t actually answer the question. I would have to better understand the mechanism behind the link to adjuvant and autoimmunity. I guess I can see bystander activation, where the dangerous context induces the dendritic cell to present self antigens, but that’s just off the top of my head.
Yes, they should be added. It can increase the effectiveness of the vaccine while at the same time increasing the number of people we can vaccinate. As far as I know, the few cases of GB syndrome and such aren’t directly tied to adjuvants - I don’t think we’re quite sure what happens in those cases, but from what I understand the problem hasn’t been prominent at all in the last decade or two - I’m not even sure if that 1-5 per 100,000 number is accurate.
As far as I’m aware, there’s no good evidence that we shouldn’t be using adjuvants. Most of the hysteria surrounding them simply comes from anti-vax tards who try to make any part of vaccines sound dangerous.
Thank you for your expertise and explanation. It’s not only fascinating, but it’s refreshing to get a look into the mechanisms from the folks who are actually doing the real work. In other words, it’s really cool.
You should shower more such information upon us, but I guess it’s difficult to work the phrase “dendritic cell” into most political conversations.
Thanks, I didn’t even realize I posted this under MPSIMS. :smack:
I also mis-wrote, now in retrospect, and obfuscated the meaning. 1-5 in 100,000 are affected worldwide by GBS as it is. Since it is an autoimmune disease, what effects would this have?
and lastly thimerosal is a preservative. In the U.S. there are two types of shots you can get, the single dose ones, and the multidose ones. The multidose ones are for the hospital, and thimerosal merely prevents contamination. You can request the single dose ones, those do not have thimerosal.
I’m glad someone corrected me in the thimerosal, since even though I knew it is/was added to vaccines, I thought it was as an adjuvant (not as a preservative)… Although I am curious to know if they’ve done studies to see if thimerosal also acts in that capacity.
Hadrian, just to correct, are you talking specifically about the H1N1 vaccine? Because adjuvants are still used in other types of vaccines.
I do want to note that making a vaccine is not an easy or cheap thing in many cases, especially when it has to undergo approval by a regulatory agency. It is also possible that whoever makes the adjuvated H1N1 vaccine has decided it is not worth the effort to get it through the FDA steps to get it approved, when there is already a nonadjuvated, approved H1N1 that should be doing its job.
The more I think about it, the more pulling adjuvant out of vaccines is like making cars safer by removing the wheels. Sure, they would be safer, but then that would defeat the purpose of having them in the first place.
Whenever I get something like a drug or vaccine I do the cost benefit analysis and it seems to be a no brainer. Yes, there is the possibility of something disasterous, but I’m willing to accept that.
I did get the H1N1 and get the flu vaccine every year. And my newborn child is getting all of his vaccinations exactly as scheduled. As an immunologist at a pharmaceutical company, I would have to be the worst father in the world if there were actually something to any of the vaccine conspiracies!
Well, yes, adjuvants are used in other applications, but I refer only to the current addition in the case of the H1N1 vaccine. To the best of my knowledge, thimerosal is purely a preservative.
To every issue, there’s always two or more sides. The FDA did not recommend the use of adjuvants because it is, according to them, a added level of complexity.
To play devil’s advocate, I can think of a couple examples for not using adjuvants. Not that I am implying that they are unsafe, but we can all learn something from Thalidomides. Maybe it’s best to err on the side of caution?
If the OP’s right about the H1N1 vaccine not having adjuvants and you are as well about vaccines requiring them to work, what would the point of administering a vaccine that doesn’t have them be?
It would depend on the vaccine. A live attenuated vaccine would cause it’s own danger, and thus adjuvants would likely be unnecessary. But, these vaccines are obviously less desirable from a standpoint of safety and specificity.
Without adjuvant, you are certainly going to have H1N1 cellular reactivity. Give you the vaccine and I’ll be able to detect vaccine H1N1 specific antibodies and T cells. But, there is a threshhold that has to be reached in order for this cellular effect to be clinically relevant, and that may well be very different for every person. Remember, you already have H1N1 specific T cells in your body right now. Your T cells are essentially sporting reactivity against random antigens, and when they see the one that actually fits, they react. But, these “naive” T cells have a MUCH higher threhhold to reactivity than memory T cells. How many memory T cells are enough? I don’t have the answer to that.
So “efficacy” depends on your standpoint? Clinical efficacy is not the same as cellular efficacy.
The link that Karl provided notes that adjuvants have been used in vaccines for more than 70 years. The record of safety of the vaccines involved (i.e. DTP) has been excellent.
Adjuvants have been a target of antivaxer groups lately. It’s part of their strategy of trying to scare people about “toxins” in vaccines. Squalene (used as a flu virus adjuvant in some countries, and also a compound found naturally in the body) is the current bugaboo. It, like other adjuvants in use, has a good safety record. Adjuvants are not used in U.S. seasonal flu vaccines or the H1N1 vaccine, but I wouldn’t hesitate to get immunized against the flu if it were thought necessary in the future to optimize the immune response to flu vaccine through the use of adjuvants.
The preservative thimerosal has been phased out of nearly all vaccines; you can get a thimerosal-free flu shot if you want, but thimerosal has not been linked to any health problems either.
But of course you are. The question is, on what grounds?
This is not a good example for your purposes. It was the FDA (in particular a scientist named Frances Kelsey) who kept thalidomide from going on the U.S. market until adequate safety studies had been done.
In the case of H1N1, naturally that’s been the government scientists’ position - a vaccine not previously used, with or without adjuvant, needs to be adequately tested. We base public health policies on good research and careful evaluation of the evidence.
If your “devil’s advocate” position is that we shouldn’t use adjuvants in any vaccines, you have not begun to make any sort of case.
Mostly I’m playing DA because most people that have posted on here are for the addition of adjuvants into the flu vaccine. I want to balance that out, and get the other sides perspective, but turns out, my argument was half-assed.
In regards to the FDA approval. The FDA did not approve them for use in the general sense, only for emergency. That mean’s they have not approved it, or not not approved it. (Confusing syntax, hangover Sunday)
I also am not implying that they are unsafe, merely that all exhaustive clinical testing ought to be finished before it is approved for the general public. Which then led to my example of Thalidomides. The FDA did not approve of them back in the 1950’s because they were none too sure about the clinical tests of the drug.
Actually I see only one poster who says flat out that he wants adjuvant added to flu vaccine. The rest of the comments deal with various aspects of using adjuvants in vaccines.
The first article you linked to includes the following:
*"One of the adjuvants used in H1N1 vaccines, MF59 produced by Novartis, has been used in seasonal flu vaccine in Europe for years and both H1N1 adjuvants have been reviewed in large studies involving tens of thousands of people, said Martin Friede, a scientific officer focused on adjuvants at the Initiative for Vaccine Research at WHO.
“In both of these very large studies no adverse affects were detected,” he said. “It’s a bit of a surprise to see how the public opinion is so opposed to adjuvants because the scientific evidence is that the adjuvants are very safe.”
One of the ingredients in the H1N1 adjuvants, called squalene, was linked in the past by media reports to Gulf War Syndrome, a link that has not been backed up by any scientific data, said Friede. An investigation into the allegations found that none of the vaccines given to U.S. troops during the Gulf War even contained squalene, according to the FDA."*
Neither article contains any evidence that vaccine adjuvants cause health problems, other than possibly increasing the incidence of local reactions like swelling at the vaccination site.
I did note in one of the articles a major facet of the reasoning behind not including any adjuvant in H1N1 vaccine in the United States - and that was to assure that as many people as possible got vaccinated. Antivaxers’ misinformation campaigns have succeeded to some extent in raising a general level of uneasiness about vaccines. Add to that the apparent increase in incidence in Guillain-Barre syndrome among those vaccinated against swine flu in the '70s, and the government saw the need for even more caution than usual in approving H1N1 vaccines.
Caution and proper testing are essential. What gets to be problematic are never-ending calls for this and that study by people who will never be satisfied with any research that doesn’t back their suspicions. We see this coming from the vaccines-cause-autism crowd, and all it does is help discourage parents from getting their kids immunized while distracting attention from research into the true causes of autism.
Did you read the Nature article?
Alum, the world’s most widely used
adjuvant, got its start in the 1920s
when vaccinologists found that mixing
it into their preparations gave a boost
to the diphtheria vaccine. Researchers
then proposed that it worked by
glomming onto vaccine components,
causing them to be released slowly into
the bloodstream.
That theory held for 80 years. It is
only now falling by the wayside, as
immunologists get their hands on alum,
a term for various immune-activating
aluminum salts.
“Alum has been used in billions of
doses since 1920,” says Rino Rappuoli,
head of research for Novartis Vaccines
in Sienna, Italy, “and, up until about
a year ago, we had no clue about the
mechanism of action.”
A 2008 study by Richard Flavell
at Yale University in New Haven,
Connecticut and his colleagues helped
to crack open alum’s secrets. Their
research suggests that alum activates
a complex of proteins in immune
cells dubbed the ‘inflammasome’.
Mice lacking the inflammasome did
not respond to alum, although other
adjuvants still worked (Nature 453,
1122–1126; 2008).
In response to alum, the
inflammasome seems to cleave and
activate certain immune-stimulating
proteins, such as interleukin-1β and
interleukin-18. These proteins are
Illuminating alum
thought to subsequently bump up the
body’s production of antibodies.
The new findings from Flavell and
his colleagues, along with other studies
implicating the inflammasome, potentially
explain why alum is good at prompting an
antibody response. A separate study in
2008 suggested that alum may initiate this
response partly through the induction of
cellular damage. Cells damaged by alum
were shown to release uric acid, a known
trigger of the inflammasome (J. Exp. Med.
4, 869–882; 2008).
But subsequent research has
muddied the waters. For instance, other
immunologists, such as Philippa Marrack at
the University of Colorado Health Sciences
Center in Denver, have found evidence that
alum works just fine as an adjuvant in the
absence of inflammasome activity (Eur.
J. Immunol. 38, 2085–2089, 2008; Nat.
Rev. Immunol. 4, 287–293; 2009).
“In trying to understand the molecular
mechanism of adjuvants, we will find a
lot of redundant mechanisms, so I’m not
surprised there is a controversy,” says
Rappuoli.
Marrack and other immunologists are
using standardized reagents to help work
out the discrepancies, which may have
arisen because of differences in alum
formulation and the analysis of the immune
response. Ultimately, researchers may be
able to design more effective alum-based
adjuvants, she says.
Charlotte Schubert, Washington DC
Sorry, the formatting’s a bit off, copied it straight from the article. So the only viable argument against adjuvants is just that they are simply not completely tested, but preliminary evidences and tests show that it probably is?
Another reason to not use it, from a manufacturing standpoint, at least, if not immunology… how much the adjuvants would help boost the immune response, to levels that are considered effective? If a nonadjuvant vaccine works well, what is the incentive to go through the research, trials, and processes of getting an adjuvated one done?
