Prior Approval for ASO3-Adjuvanted Vaccines?

I was asked if any other vaccines have been approved that contain ASO3. The answer is yes, and no.

No licensed US vaccines have ever contained this adjuvant. I am not aware of its presence in licensed vaccines used in any other countries, prior to the H1N1 adjuvanted vaccines.

However, ASO3 was approved by the European Medicines Agency (EMEA) for a BIRD FLU (H5N1) vaccine. Actually, it was approved for use in two bird flu vaccines in Europe: a "prepandemic" vaccine, called Prepandemrix, and a pandemic vaccine, Pandemrix (same name as GSK's new and different swine flu vaccine). A Canadian briefing paper said it was also approved for use in Asia.

I blogged about so-called prepandemic vaccinations once before. What is a prepandemic vaccine? You might well ask.

Remember, those in the business of threat assessment and pandemic planning have to find threats and develop responses to them. That is what they are paid to do. (The 8 year old Department of Homeland Security has 200,000 employees, for example. Threat assessment and response is very big business.)

BARDA (the Biomedical Advanced Research and Development Authority) is a new federal agency within HHS whose job is to support the research, development and procurement of such medical products that can serve as the response. BARDA was created to deal with bioterrorism initially, so it has a quasi-military, "can do" flavor, compared to our public health agencies, which have more grounding in clinical medicine and risk-benefit analysis. BARDA buys the pandemic vaccines.

Even though there never was a bird flu epidemic, considerable planning and expenditures went into responding to the possibility of one. One result was the production of huge quantities of bird flu (aka H5N1 influenza virus) vaccines, both in the US and elsewhere. GSK discusses its novel adjuvants and development of bird flu vaccine here.

Bird flu did kill over 50% of those infected. So our governments bought us vaccines. But they didn't know if the vaccines would work. That uncertainty helped make the case for adding a novel adjuvant. The adjuvants were billed as expanding the immune coverage provided. If they didn't work against whatever bird flu happened to emerge, they were still supposed to provide some initial immunity, such that a second, better targeted vaccine would generate much higher levels of antibody, specific to the right virus, than if there had been no initial vaccine.

Of course, this claim was theoretical, since until a bird flu epidemic occurred, you wouldn't know whether the old bird flu vaccines would provide any immune advantage--but it gained traction nonetheless.

The next idea to gain some traction was that since a bird flu epidemic would be devastating, maybe countries should just go ahead and give their citizens a first dose of bird flu vaccine to get us all primed in advance for the epidemic. After all, huge stores of vaccine had been produced. And all that would happen to those stores otherwise would be to reach their expiration dates. This was what our worldwide pandemic vaccine experts had been nattering about when the swine flu appeared. For example, from the state of Michigan Pandemic Vaccination Planning Guide:

"In the absence of a virus specifically matched to the pandemic virus, it is hoped that pre-pandemic H5N1 vaccine will have sufficient cross-reactivity to afford some protection to these groups.

The goal is to have sufficient vaccine for 20 million persons (at 2 doses per person). The trigger for using pre-pandemic vaccine has yet to be determined but would likely be evidence that an H5N1 virus had acquired the ability to spread efficiently from person to person. However, because the stockpiled vaccine will eventually lose potency, discussion has also occurred regarding possible administration to selected groups before the onset of a pandemic."

Given the above, how the experts would respond to swine flu was practically a foregone conclusion.

Naturally, they took their pandemic plans for bird flu (with mortality rates greater than the Black Plague) and forcibly fitted those plans to swine flu (arguably no more severe than seasonal flu). When swine flu first appeared, the Obama administration was new and there was no appointed HHS secretary, so the pandemic planners at DHS and DHHS likely had wide latitude to drive the program's direction.

That is why a huge vaccine campaign was undertaken, and why novel adjuvants were going to be used, without much question, even in the early planning, even in the United States. Here is a PPT presentation from Florida public health officials made in July, showing how H1N1 vaccines made by Sanofi-Aventis, CSL and GSK were all to be prepared for use with ASO3. The Novartis vaccine was to contain MF59. Probably Novartis, contracted for the biggest supply of swine flu vaccine, is "Company 3" described by Nicole Lurie in my last blog post.

Once swine flu is a thing of the past, watch to see if the idea of "prepandemic" bird flu vaccinations catch the fancy of our public health agencies. If the swine flu vaccine program is judged successful, bird flu vaccines may be next, with or without an epidemic. If there are serious safety or efficacy problems with swine flu vaccines, the bird flu vaccine will be shelved for awhile longer.

UPDATE: The Independent discusses costs and profits for swine flu vaccine and drug suppliers.