FluMist: Reasonable Vaccine Option or 'Last Resort' for the Upcoming Flu Season?

Paul A. Offit, MD


June 09, 2018

Editorial Collaboration

Medscape &

Hi. My name is Paul Offit, and I'm talking to you today from the Vaccine Education Center at the Children's Hospital of Philadelphia. I want to talk about some contention about the use of the live-attenuated influenza vaccine known as FluMist. On the one hand, you have the Advisory Committee on Immunization Practices (ACIP), which advises the Centers for Disease Control and Prevention (CDC), recommending that the FluMist vaccine be used this coming year in the same manner that one would use the inactivated vaccine. Or said another way, you could use either vaccine.

But that's not what the American Academy of Pediatrics' (AAP) Red Book committee stated. They stated that they preferred the use of the inactivated influenza vaccine, and that the FluMist vaccine should only be used as a "last resort."[1] Let's talk about the data that are behind those two recommendations and see if we can make sense of them.

FluMist was first licensed for use in the United States in 2003 for those aged 5-49 years. In 2007, it was recommended for all of those between 2 and 49 years of age. The way that the vaccine is made is that it comes from two cold-temperature-adapted influenza viruses that were created in the 1960s, into which one then reassorts the hemagglutinin neuraminidase genes that are going to be prevalent for the coming season. In studies done in 2006 and 2007, that vaccine appeared to be better than the inactivated influenza vaccine.

For that reason, in 2014, the ACIP gave FluMist a preferential recommendation over the inactivated influenza vaccine. Unfortunately, in the 2013-2014 season, 2014-2015 season, and the 2015-2016 season, FluMist actually underperformed compared with the inactivated influenza vaccine, especially for the H1N1 strain; and for that reason, the ACIP withdrew its recommendation to use FluMist.

This year, 2018, FluMist is back on the market. The problem that FluMist suffered is that it is a vaccine that contains four different strains and it's given to a mucosal surface—a nasal spray vaccine. If you are going to do that, you have to make sure that all four strains replicate equally. The problem with FluMist was that the H1N1 strain (the so-called A/Bolivia strain) had a replication fitness problem. It didn't replicate nearly as well as it needed to induce immune response.

Now, all of the data to date support the fact that the company that makes FluMist has resolved that problem. They've proven it by showing that this new strain, the A/Slovenia strain, as compared with the A/Bolivia strain, reproduces itself very well in human nasal epithelial cells. Previously, the company had been using Madin-Darby canine kidney cells to look for replication, which were not nearly as predictive as human nasal epithelial cells.

Second, instead of using a fluorescent focus assay, which is not a very good measure of spread of virus from one cell to another, the company now uses what is called a TCID-50 (50% tissue culture infection dose) assay, which also shows that the virus can replicate well. Furthermore, the company has shown that the immune response for the new A/Slovenia strain is much better than that of the A/Bolivia strain—similar to what had been seen before they had the H1N1 problem.

So I think the AAP was wrong, frankly, to say that FluMist should only be used as a last-resort vaccine for influenza. Rather, they should have gone along with what the ACIP said, which was that these vaccines can now be used interchangeably for persons aged 2-49 years.

Thank you for your attention.