TORONTO - Six months ago, most Canadians probably didn't know what a vaccine adjuvant was.
But now, as Canadians and many Europeans mull over whether to line up for an H1N1 flu shot that includes an adjuvant, many have Googled this addition to their vocabularies. And lots are wondering whether they are comfortable with the idea of having vaccine mixed with one of these additives injected into their arms.
Some question whether H1N1 vaccine with adjuvant is safe for children. It's an issue that's bothering Will Murphy, the father of a 23-month-old boy.
"We have deep concerns about making sure we do the right things that are the safest for him," says Murphy, a marketing professor at the University of Saskatchewan in Saskatoon.
He has a lot of questions. And he's disconcerted by some of what he's read on the Internet. "The wonder of the web today, of course, allows us perhaps more information than we end up comfortable with."
So as Canada embarks on its H1N1 vaccination program, let's explore what these compounds are, why Canadian vaccine will contain an adjuvant and why your arm might be a little bit sorer this year if you decide to get a flu shot.
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, tetanus 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.
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.