COMMENTARY

New Adjuvanted Flu Vaccine: No Concerns About Narcolepsy

Paul A. Offit, MD

Disclosures

December 11, 2015

Editorial Collaboration

Medscape &

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Hi. My name is Paul Offit. I'm talking to you today from the Vaccine Education Center here at The Children's Hospital of Philadelphia.

Of interest, in the past couple of months, an influenza vaccine is now on track for licensure. It's called Fluad®. It is different from all of the other vaccines that we have ever used in this country in that it contains an adjuvant named "squalene." Squalene is derived from shark oil. We all have squalene in our bodies. It's part of cholesterol synthesis.

Adding squalene to an influenza vaccine is the third time that an adjuvant has been used in the United States. The first adjuvant was aluminum salts, which are contained in a number of vaccines. The second was monophosphoryl lipid A—a detoxified lipid A product that is present in one of the human papillomavirus vaccines. Squalene will be the third adjuvant used in this country.

Squalene has been used in other countries, and it's an excellent adjuvant. If you look at the data with the squalene adjuvant in influenza vaccine, you can see that in people over age 65 years, it induces a better immune response than the inactivated influenza vaccine that is not adjuvanted. And it's more likely to induce broader cross-reactivity when there is a mismatch of strains. For all of these reasons, I think this will be an excellent product.

The issue, however, that no doubt will come up is that, in 2009, associated with the pandemic influenza that swept across the world, a squalene-adjuvanted influenza vaccine was used in Europe as well as in Scandinavian countries. It was called Pandemrix®, and it was found to be a rare cause of narcolepsy, which is a disorder of wakefulness. Depending on which country you looked at, the incidence of narcolepsy was from 1 in 16,000 to 1 in 50,000 people who got that vaccine.

However, another squalene-adjuvanted pandemic influenza vaccine that was used, called Focetria®, did not cause this problem.

In a recent paper in Science Translational Medicine,[1] researchers explained the difference between those two vaccines. The difference was that whereas Pandemrix contained a fair amount of influenza nucleoprotein, Focetria didn't contain that influenza nucleoprotein. And the nucleoprotein was the key because it appears that nucleoprotein has molecular mimicry with at least one of the receptors for hypocretin, the product made by cells in the hypothalamus that is associated with wakefulness. Apparently, it was a phenomenon of autoimmunity. Antibodies directed against the cells that produced hypocretin were made, and these antibodies destroyed those cells and caused the permanent disorder of narcolepsy.

Some people will fear squalene, especially squalene-adjuvanted influenza vaccines, because of the experience with narcolepsy. Realize, however, that the problem is not the squalene but rather the squalene plus the influenza nucleoprotein. It's an avoidable problem. All one has to do is to make sure that there is no contaminating influenza nucleoprotein in the squalene-adjuvanted flu vaccine. That problem has been fixed.

Hopefully, this information will help you in trying to deal with the inevitable concerns about squalene-adjuvanted influenza vaccine in the United States. Thank you.

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