September 14, 2009

Helen Branswell, Medical Reporter, THE CANADIAN PRESS

TORONTO - A shot of swine flu vaccine that is about a third of the size of a standard dose is protective when boosted with an additive called an adjuvant, Canada's pandemic vaccine manufacturer said Monday.

The ability to use one dose - and a small one at that - should both speed up the time it takes to fill an individual country's order and stretch limited global supplies of pandemic vaccine, experts have said.

Results of a clinical trial conducted in Europe by GlaxoSmithKline showed that 98 per cent of adults who received a single shot containing 5.25 micrograms of vaccine and the company's AS03 adjuvant had a spike in antibody levels thought to signal protection.

While a number of other companies have already shown that one shot of pandemic vaccine will likely protect most people, this is the smallest dose size that has been shown to be protective. Other companies have demonstrated that 15 micrograms of vaccine without adjuvant or 7.5 micrograms with adjuvant will probably protect against the new virus.

However, this trial does not answer the question of whether the dose GSK hopes to sell to Canada will work.

The company plans to sell a formulation containing 3.75 micrograms of antigen (vaccine) plus adjuvant. A statement from GSK said the formulation tested was "comparable to the expected final formulation of the adjuvanted vaccine."

An influenza expert said that may be true, but the company still needs to generate data showing that the smaller dose will work as well.

"The truth of the matter is if you have good immunogenicity with a 5.25 mcg dose, then, yeah, probably 3.75 mcg is going to be not bad. But it's clearly better to have data with the real dose," said Dr. Allison McGeer, an influenza expert at Toronto's Mount Sinai Hospital.

"The best data is obviously immunogenicity data that is as close as you can get to the actual vaccine that's being produced."

The Public Health Agency of Canada said these results and others released last week are promising but are not the final answer on dosing requirements.

"These preliminary results to date show that the vaccines help to protect people from the H1N1 strain. We will need additional data before making any final decisions about safety and effectiveness," Jirina Vlk, a spokeswoman for the agency, said in an email.

Though evidence is mounting that one shot of vaccine will protect adults against the novel H1N1 virus, Vlk said the public health agency is still hedging its bets. "Prudence dictates that we continue planning for a two-dose regime until we have more conclusive information on which to take a decision."

GSK did not explain in its release why it tested 5.25 mcg of vaccine with adjuvant and 21 mcg without. Neither dose size is among those routinely chosen for testing. Generally speaking clinical trials look at doses that are some fraction or multiple of 15 mcg, the amount of antigen per strain contained in a seasonal flu shot.

But the company said in an email that the clinical trial was started before standardized reagents - tests used to determine the concentration of vaccine - were available from the World Health Organization. Rather than wait for the standardized reagents, the company used alternative tests that appear to have led to higher-than-intended doses.

"Based on GSK's experience with its adjuvants systems, we do not anticipate that there will be any significant difference in the immune response elicited by the final formulation," GSK said in the email.

The GSK release also did not reveal whether there were any side-effects seen or how frequently they were reported. Studies done by other vaccine manufacturers have reported a side-effect profile for swine flu vaccine that is similar to what is seen with seasonal flu shots, mainly sore arms.

The release did say, though, that the findings have been shared with regulatory authorities and additional studies will be done in Europe, Canada and the United States.

"This trial provides encouraging data on the potential use of a single dose of our pandemic vaccine," said Jean Stephenne, president GlaxoSmithKline Biologicals.

"Our next step is to complete this trial, as well as 15 other studies in our clinical development programme for the vaccine."

The trial took place in Germany and involved 130 healthy volunteers 18 to 60 years old. GSK has two flu vaccine manufacturing facilities - one in Dresden, Germany and the other in St-Foy, Que. The latter will supply Canada's pandemic vaccine.

The company said 98 per cent of volunteers who got the small dose with adjuvant had antibody levels that exceeded what regulatory agencies consider is protective when tested three weeks after the shot was administered. Among those who got the larger dose of unadjuvanted vaccine, 95 per cent reached the same threshold.

Last week Novartis, Sanofi Pasteur and CSL Limited announced that their vaccines were protective with a single dose. And studies done by the U.S. National Institute of Allergy and Infectious Diseases showed that antibody levels reached the predicted protective threshold within eight to 10 days after one shot, which is very quick for vaccine.

Source: http://www.whistlerquestion.com/arti...template=cpArt