Adjuvant questions answered

[HonestRN]

It's important to remember that adjuvants are not approved for us in the US

Q: What is an adjuvant?

A: The word-which is pronounced ADD-joo-vant-comes from the Latin adjuvans, meaning "to help." That pretty much tells the tale.

Adjuvants are additives that help the immune system respond to a vaccine. They seem to work by enlisting more parts of the immune system in the fight against targeted virus or bacteria than do vaccines that don't contain adjuvants.

The concept may seem new to us, but adjuvants have been used in vaccines for decades. The most commonly used adjuvant, alum or aluminium salts, is used in some currently marketed vaccines, such as some made to protect against diphtheria, tetorifice and pertussis.

Even the earliest vaccines contained adjuvants, albeit inadvertent ones.

Current manufacturing processes place a heavy emphasis on purification processes. But in the old days, vaccines were far more of a soup of viral or bacterial bits and bobs.

Those vaccines were more "reactogenic"-meaning they caused a lot more local reactions (a.k.a. sore arms) than modern vaccines do. But immunologists admit they probably also worked better.

"The general impression was that when you left all the 'junk' in there-which isn't really junk, it's just parts of the virus-and you didn't purify it, that you were probably providing a subliminal adjuvant in your regular vaccine that was never listed as being an adjuvanted vaccine," says Dr. Anthony Fauci, head of the U.S. National Institute of Allergy and Infectious Diseases.

Q: Why is Canada buying adjuvanted vaccine?

A: The World Health Organization asked countries to use "antigen sparing" approaches to pandemic vaccination. Using an adjuvant is one of the main antigen sparing options available. (Antigen is the vaccine component that elicits the immune response.)

One of the major benefits of adjuvants is that they allow vaccine to be stretched. When you add an adjuvant to H1N1 vaccine, a dose that would have vaccinated one person can be used to protect four.

Global flu vaccine production capacity is limited. And while affluent countries like Canada, the U.S., Japan and those of Western Europe have vaccine contracts, most countries don't. So the more adjuvanted vaccine developed countries use, the less antigen they need. And that means more will be available for developing countries.

Q: So we're using vaccine with adjuvant to benefit someone else?

A: That's part of the reason. But it is also true that Canada can get its entire vaccine order a lot quicker if it takes the equivalent of a quarter dose to vaccinate each individual.

Studies have shown there are benefits to individuals as well. For instance, adjuvanted vaccine offers more of what's called cross-protection. When flu viruses mutate, vaccine can become less effective because it's no longer on target. But a vaccine with adjuvant can produce a good immune response to viruses that are similar but not exactly the same as the vaccine target.

There's also a chance one dose of adjuvanted vaccine would suffice for everyone, even young children. Preliminary data released last week by GlaxoSmithKline-the makers of Canada's H1N1 vaccine-shows even young children got what looks like a protective immune response from one dose of vaccine.

Children under 10 are currently slated to get two shots, at least 21 days apart-a regimen that will be a figurative pain for parents and a literal one for kids. But Canada's chief public health officer, Dr. David Butler-Jones, says that recommendation may be revised if further data supports a one-dose approach.

Q: But what's this about adjuvanted flu shots hurting more?

A: Let's be clear. We're not talking about excruciating pain, we're talking about a bit more of a sore arm than usual-though some years seasonal flu vaccine packs a bit of a wallop too.

About the pain: The adjuvant causes some inflammation at the site of the injection, a process that activates parts of the immune system.

"Invariably adjuvants give you more pain, swelling," Fauci says. "But as far as prolonged or long-term systemic effects, there have been no good data to indicate (that) at all. In fact, the data to the contrary have shown, that it's really quite safe."

Q: What is the safety record for adjuvants?

A: Alum has been used safely for decades. But it doesn't work particularly well with influenza vaccine. So several flu vaccine manufacturers have developed new adjuvants. Novartis has one called MF59. GSK has one called AS03, which is being used in Canada.

MF59 has been used for more than 10 years in flu vaccine in Europe. According to a fact sheet from Novartis, the adjuvant has been tested in 28,000 people in 60 clinical trials and has been given to more than 40 million people, albeit mostly older adults. It's used in a vaccine designed to help seniors-whose immune systems are waning-get good protection against influenza.

AS03 is newer and isn't in GSK's seasonal flu vaccine. But the company has been testing an AS03-boosted vaccine to protect against H5N1 avian flu and a total of 41,000 people have received AS03 in clinical trials, says Dr. Thomas Breuer, head of global clinical development and chief medical officer of GSK Biologicals.

In addition, as of late last week 150,000 people had received GSK's H1N1 vaccine containing AS03.

To date, there have been no red flags.

Q: What are adjuvants made from?

A: There are a variety of adjuvants, but the ones used with flu vaccine are oil-and-water emulsions. The recipe may change a little from company to company and the mechanism of action may differ a little as well, says David Wood, co-ordinator of the quality, safety and standards team of WHO's department of immunization, vaccines and biologicals.

GSK's Breuer says AS03 is made from Vitamin E, polysorbate (a widely used component of medicinal products) and squalene, an oil.

Q: Isn't squalene dangerous? Didn't it cause Gulf War Syndrome?

A: No and no.

It may have a nasty sounding name, but we all have squalene (pronounced SKWAY-lean) in our bodies. We need it to synthesize cholesterol and steroid hormones. And the stuff is ubiquitous-it is found in all animals, in plants, and in a variety of foods, cosmetics, over-the-counter drugs and health supplements, according to the World Health Organization.

"It is part of our natural metabolism that allows us to make the kinds of molecules that enable us to survive," says Dr. Paul Offit, an immunologist and vaccine expert at Children's Hospital of Philadelphia.

"Take squalene out of your body, and you die. Take squalene out of Girl Scout cookies and they don't taste as good."

As for the supposed Gulf War Syndrome link, it isn't true.

The claim is that anthrax vaccines given to U.S. soldiers fighting in the Gulf War contained squalene and generated anti-squalene antibodies that triggered disabilities. But the vaccines given to those troops did not contain squalene, the WHO and others have reported.

And a study published in 2006 showed that anti-squalene antibodies can be found in the blood of people who have never been vaccinated with a vaccine containing squalene.

"The objective scientific evidence is that these things are safe. That they are not linked with Gulf War Syndrome. That they don't promote autoimmune disease. That's what the objective scientific evidence says. But it's not what you read on the blogs and on the Internet," Wood says.

Q: What's that about autoimmune disease?

A: "Whenever you induce a heightened immune response, there's always the concern that you're going to trigger aberrant immunological reactions that lead to autoimmune diseases," says Fauci. "But thus far the adjuvants that have been used in Europe ... have a very good track record of safety."

The head of GSK's adjuvant program, Dr. Nathalie Garcon, says the adjuvants don't rev up the immune system throughout the body, they act only at the site of injection. The immune messengers created there do travel from the injection site, but that's not the same as turning up the valves everywhere.

A trial Garcon did neatly illustrates the point. Some people were given flu vaccine with ASO3 mixed in, while others got a shot of flu vaccine in one arm and AS03 in the other. When the vaccine and adjuvant were not given together, the boosting effect was not seen.

Q: Squalene used commercially is sourced from shark's liver. Does that mean people with fish allergies should avoid this vaccine?

A: Garcon says no. Allergies are a reaction to proteins, but squalene is a lipid (fat).

"There's no known allergy to any lipid whatsoever. And because squalene is a constituent of the human body, you don't react against it," she says.

http://www.torontosun.com/news/canada/2009/10/26/11531076.html

thanks to FLA_MEDIC at http://afludiary.blogspot.com/