Squalene is a 30-carbon branched structure made from isoprene units in the production of cholesterol and other endogenous compounds such as glucocorticoids and sex steroids.
We all have squalene in our bodies. We NEED squalene. All mammals make squalene. Even fungi make squalene (for a compound called ergosterol that is required in their cell membranes).
So ubiquitous is squalene is that it is extracted commercially from shark liver oil. Squalene is intentionally added to cosmetics sold as "natural."
Squalene is also a component of a vaccine adjuvant that has been used for over 10 years in Europe but is still pending approval in the US for use in the H1N1 flu vaccine.
In the context of immunology, an adjuvant is a chemical or combination of chemicals used to improve the immune response to vaccines.
But squalene is already in our bodies. We make the stuff. A vaccine with squalene will just be adding a little more squalene into our bodies.
It is in olive oil too. I was at this local vaccination discussion recently, and it was full of anti-sci cranks and CTers. I had snarked on squalene during the session.
One of the cranks was following me out the door, trying to help me to understand how scary squalene was. I told him that my liver was full of squalene as we speak. And I also said, "Oh, I hope you didn't have the olive oil at lunch...um...it's full of squalene...." He looked as if he's swallowed a lemon suddenly.
What's really fun is to have these facts at hand for situations like that :)
If it's so ubiquitous, how does it work as an adjuvant? Wouldn't our bodies just recognise it as more of ourselves? Or does it help something else in the adjuvant attract the attention of our immune system?
I seem to recall that it's a major component of earwax, too.
I used to work with both squalene and squalane. Oooooooh!!!! I'm so scared of the stuff. [/snark]
Nice one. Must remember to use it on the next nutter I may unfortunately run into.
"You don't like squalene? STAY AWAY FROM THE OLIVE OIL! BOOGEDY-BOOGEDY-BOOGEDY! "
Wow. For all the antivax/conspiracy nuts put up a hue and cry about squalene, even I sort of figured there must be something vaguely dangerous about it. But no, just another vacuous antivax lie.
I think the squalene story started with gulf war syndrome: one of the theories was that one of the vaccinations soldiers received was responsible. A lot of the vaccination records 'went misssing' for the deployed troops, and there were rumors that squalene was used as an adjuvant in one of the anti-biowarfare vaccines ... There were some studies looking at it, and If I remember correctly, troops who had GWS symptoms generally had anti-squalene antibodies whether or not they were ever deployed to the gulf; troops that did not have GWS symptoms did not have anti-squalene antibodies whether or not they were deployed. Which might point more toward autoimmune problems than vaccine issues, I suppose.
Okay - but is it natural to mix this naturals compound with some natural fragements of natural influenza virus and inject it into our natural muscles? I don't think it's all that natural...
So, let's stick to EbM and what we know about the effects of squalen-adjuvants and not rant about naturalness. (remember the CAST study? it seems natural to suppress arrythmias with antiarrhtymcics - and it seemed so unnatural that thes pills killed people, but they did!)
What #2 said. Would really like an explanation of how something that is ubiquitous already can be an effective adjuvant.
An i.m. injection places the ubiquious substance in an unusual space inside the body. I don't wonder that the immune system takes on...
All this does not make a squalen-containing vaccine better than one without. At least it produces more pain at the injection site.
Wired has a followup on squalene here.
If you want to know more about the Gulf War connection, click through to the last link on the page (where is says "didnât come from the vaccine at all").
I will continue to read your blog, It was interesting to read, thanks a lot!
Although it is not the information I needed.
Not answering for Abel, just adding my 2 cents: probably floating your proteins in little oily nugget makes it look more like something the immune system should respond to. And one paper I read suggested the uptake of antigen by immune system responder cells was enhanced by the presence of the squalene.
Ironically, IIRC the U.S. has been criticized for not using adjuvants in influenza vaccine, since that reduces the vaccine available to the rest of the world.
If you Google "shark liver oil" (a major source of squalene) you'll find Big Placebo websites selling it as an immune-system booster, some of them specifically touting the squalene content. One claims it will help with cancer and AIDS. http://www.nulifeuk.co.uk/
SLO is also one of the active ingredients in Preparation H, which means that tens of millions of people have been stuffing it up their butts for the better part of a century without apparent ill effect.
Sorry for the radio silence, folks. I was looking for a good adjuvant review and found this one written by Amy McKee in Philippa Marrack's group at National Jewish Hospital/Univ of Colorado Health Sciences Center in Denver, one of the top immunology labs in the US. It's well-written and details what we do and don't know about the mechanisms of action of adjuvants.
Adjuvants can act in several nonmutually exclusive ways to augment the adaptive immune response and to generate effective immunological memory. Many of their effects seem to be on antigen-presenting cells such as dendritic cells (DCs). Thereby adjuvants can affect the migration, maturation, antigen presentation, and expression of costimulatory molecules by DCs, and these events in turn improve the responses to antigen of T and B cells. Adjuvants, apparently via DCs, can also affect the nature of CD4 T helper (Th), CD8 T cell, and B cell responses, with some adjuvants promoting Th1-related responses and others preferentially inducing Th2-biased effects. Furthermore, some adjuvants enhance crosspresentation by DCs of MHC I-restricted antigens to CD8+ T cells. Adjuvants may also act directly on T or B cells, improving their proliferation and/or conversion into memory cells that are essential for the success of vaccines.
There's a pretty good discussion of how naturally-occurring, or intrinsic, adjuvants in the vaccine (such as non-protein components of virus) can engage toll-like receptors (TLRs). However, there are some agents that are not TLR antagonists that can enhance cellular immunity. Squalene and other lipid adjuvants appear to be in this class.
The latter end of the review discusses squalene-containing adjuvants such as MF59, AS02/AS04 and other oil/water emulsions. Hope this helps everyone.
Awesome link, Abel!
And a perfect excuse to point out that the Department of Immunology at the University of Colorado Health Sciences Center is right in the center of research aimed at improving public health through immunization.
That department's leading light is J.J. Cohen, discoverer of apoptosis and founder of the ultimately awesome Mini Med School. His lectures are hilarious, brain-expanding and not to be missed. If you care about health and live anywhere in the same region as Denver, you absolutely have to attend the MMS (held every fall) at least once. Trust me on this one.
Is there a way of manufacturing arificial squalene: the oceans are overfished and sharks are victims of overfshing. Using oil from species that we are fishing down in order to protect ourselves from disease is not ethical.
Hello friends -
The reality is, we really don't have a good idea of how squalene does what it does when included in a vaccine.
From the link provided in #16.
Despite its long use, we still do not know exactly how alum mediates its adjuvant effects
This particular adjuvant, alum, is the one most widely used (in fact, the only one used in the USA). Considering it has been used for decades and we're still scratching our heads on the hows and whys, it shouldn't be surprizing that we don't know how squalene does its business either. It turns out, since this was written, there have been some advances in understanding how alum works anyways.
I believe that adjuvants designed to invoke specific TLRs are under development, but a ways off for human use anyways. The chickens and the rats are hard at work on them though.
As far as olive oil or Preparation H as meaningful analogies to how harmless the stuff is, one might wonder if olive oil or preparation H have been shown to induce immune responses, or for that matter, if there is any difference between oral/rectal delivery and intramuscular. The body makes testosterone too; that doesn't mean you can give yourself more of it without having possibly unforseen consequences.
It seems that gross over simplifications tend to multiply when the dirty little secret of vaccines gets questioned. In a system as complicated and poorly understood as the developing immune system the details matter, and in many ways, we are still groping in the dark; albeit with one liners at hand when someone asks what we are groping for.
Jessica -- squalene can be obtained from many sources other than shark livers. Shark livers are just convenient for processing. Fortunately an increasing number of manufacturers are waking up to the danger it poses to the wildlife and turning to botanical sources. Vegetable oils are a good source.
I'm sure it could be synthesized, but it's probably cheaper to grow a field of flax.