U.S. Passes on Unlicensed H1N1 Vaccine Boosters, Despite Shortage

As of Friday, the Centers for Disease Control and Prevention said there are 38 million doses of H1N1 vaccine available, far short of the 159 million needed to cover people who fall into the highest risk groups, such as pregnant women and children.

Bruce Gellin, director for the National Vaccine Program office at the U.S. Department of Health and Human Services, called the situation “frustrating” for both patients and local health departments trying to make and keep distribution plans.

“We know the vaccine is safe and effective and we wish we had more of it now,” said Gellin. “There is more coming, but it’s not coming as quickly as we would like.”

Gellin said manufacturers have continued to tinker with the efficiency of the production of the H1N1 vaccine, making improvements to the yield, but that global influenza vaccine capacity is largely fixed, due to the number of facilities and the time-tested, but time-intensive, process of growing vaccine virus in eggs.

However, one tool for stretching vaccine supply, called adjuvants, has not been employed by the United States in this pandemic. Adjuvants are enhancers that help boost the immune response to a vaccine, allowing less antigen to be used for each dose and more doses to be distributed.

Many countries in Europe, the Middle East and Asia, as well as Canada have primarily placed orders for adjuvanted versions of H1N1 vaccine, according to Marie-Paule Kieny, director of the Initiative for Vaccine Research at the World Health Organization.

“WHO encourages the use of adjuvanted vaccine because it will help to stretch the global supply,” said Kieny, who emphasized that all safety reports for the adjuvanted H1N1 vaccine have been positive. “There doesn’t seem to be –in terms of safety — a difference.”

The H1N1 vaccine adjuvants, oil-in-water products manufactured by GlaxoSmithKline and Novartis, allow double the yield for the same amount of antigen as the unadjuvanted vaccine, according to the WHO.

While the United States uses other types of adjuvants, like alum, commonly in other vaccines, the adjuvants that are effective with the H1N1 vaccine have not been licensed in the United States. The Food and Drug Administration could have issued an Emergency Use Authorization in order to introduce an adjuvanted vaccine, said Gellin, but that option was not taken.

“We were concerned that people might be hesitant to take a vaccine that wasn’t licensed,” said Gellin. Because the H1N1 vaccine did not require a huge amount of antigen for each dose–which many people feared because of previous experience developing an H5N1 avian flu vaccine– Gellin said the unadjuvanted vaccine was still an option.

“We felt it was better to go with what we were very familiar with,” said Gellin, since the current vaccine is produced through the same process used each year for the seasonal flu vaccine.

Recent studies done on H1N1 vaccines funded by Health and Human Services have included more than 4,000 people who were given the adjuvanted vaccine. Gellin said this was an effort to gather as much information about the safety and effectiveness of the adjuvants as possible because they are a “tool in the toolbox” for dealing with a pandemic, and not because of any plans to use an adjuvanted vaccine soon. The CDC has also said there is no plan to recommend a 2009 H1N1 vaccine with adjuvant.

Tawny Buck, director of government relations for the National Vaccine Information Center, whose daughter was disabled by an adverse reaction to a whole cell pertussis immunization in 1995, said any emergency push of adjuvants through the licensing process would be very alarming to consumers.

It raises the question of “why haven’t we gotten there before and what still needs to be done to assess the safety of that?” she said.

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.

But doubts in the public have persisted, despite the results of that investigation.

“We can’t come up with answers for the Autism epidemic or our poor veterans who suffered from Gulf War Syndrome,” said Buck. “I don’t know if it’s connected [to vaccines] but I think the questions are really valid and until we get answers we can trust, people are smart to be concerned.”

As the debate over adjuvants continues in the U.S., the global H1N1 vaccine shortage continues to be a challenge for many countries. The WHO is aiming to provide H1N1 vaccine coverage for 10 percent of the population in 95 developing countries, but will likely only reach 2 percent in its first phase, beginning in November and ending in February, because of supply shortages, Kieny said.

WHO is receiving donations from manufacturers, and some richer countries, including the United States, have pledged donations as well. But U.S. Health Secretary Kathleen Sebelius said last week that donations will be put off until at-risk Americans have all had the opportunity to get the vaccine.

“There are delays for everybody, compared to what everybody thought in September,” said WHO’s Kieny.