Wednesday, August 03, 2016

FLUAD™: An Adjuvanted Flu Vaccine Option For Those Over 65


One of the problems with the regular flu shot is that it tends to provoke a less-than-stellar immune response in many recipients over the age of 65 (see Flu Shots For The Elderly May Have Limited Benefits).

Since the elderly are generally at greatest risk of severe illness or death from influenza, finding ways around this limitation has been a major priority.

On approach has been the introduction of a High-Dose flu vaccine option for seniors that contains 4 times the normal amount of antigen; 60 µg of each of the recommended strains, instead of the normal  15 µg (see CDC Q&A on Fluzone High-Dose Seasonal Influenza Vaccine).

While early results have been promising, this high antigen formula would be problematic during any kind of pandemic or novel flu scenario, as virus specific antigen will be in very short supply.

Another approach is to add an adjuvant to a normal dose flu vaccine; proprietary ingredients that  increase the recipient’s immune response and that can greatly  lower the amount of antigen needed for a vaccine.

While not approved (until this year) in U.S. vaccines, adjuvants have been used in seasonal flu vaccines in Europe and Canada for years. And the experience with nearly all of the experimental avian flu vaccines (H5 & H7) to date has been that they have little effectiveness unless they are combined with an adjuvant.

In 2014, we saw a study by the NIH: H7N9 Vaccine Candidate Works Much Better With An Adjuvant, which found - “Without adjuvant, immune responses produced by the investigational vaccine were minimal regardless of vaccine dosage.”

Adjuvants were considered for inclusion in the 2009 H1N1 pandemic vaccine - and were stockpiled by the HHS - but a paucity of safety trials on children, an abundance of unfounded Internet hysteria over vaccine safety, and adequate vaccine supplies - led the HHS to opt out of adding adjuvants at the time. 

But come the next severe flu pandemic, adjuvanted vaccines are very likely to be the only game in town.

More recently there have been concerns raised over increased levels of narcolepsy among children who received an adjuvanted Pandemrix vaccine in Europe, but another brand of adjuvanted vaccine produced no increase in narcolepsy (see Dr. Paul Offit's Medscape commentary New Adjuvanted Flu Vaccine: No Concerns About Narcolepsy).

In any event, vaccine related narcolepsy was only reported in children, and the new FLUAD™ adjuvanted vaccine will only be available for those over the age of 65.

Although it received FDA approval last fall, this upcoming flu season will be the first time an adjuvanted flu vaccine will be available for use in the United States. 

While the CDC is not recommending one type of flu shot over another, those over 65 will now have three flu shot options to choose from:

  1. Standard flu shot
  2. High-dose flu shot
  3. Adjuvanted flu shot

Given the need to use dose-sparing vaccines during any future pandemic situation, public health agencies will no doubt be watching closely to see how well this adjuvanted vaccine option is received by the public. 

The CDC has published a Q&A on this new flu shot option.

FLUAD™ Flu Vaccine With Adjuvant

This page provides information on FLUAD™ influenza vaccine.


The U.S. Food and Drug Administration (FDA) has licensed a new seasonal influenza (flu) vaccine containing adjuvant for adults 65 years of age and older. An adjuvant is an ingredient added to a vaccine to create a stronger immune response to vaccination. The new flu vaccine, FLUAD™[PDF - 270 KB], was licensed in November 2015 and will be available during the 2016-2017 flu season. It contains MF59 adjuvant, an oil-in-water emulsion of squalene oil. FLUAD™ is the first adjuvanted seasonal flu vaccine marketed in the United States.

Questions & Answers:

What is FLUAD™?

FLUAD™ is a standard-dose, three-component (trivalent) inactivated flu vaccine that contains an adjuvant. It is manufactured using an egg-based process (like most flu vaccines), and is formulated with the adjuvant MF59. An adjuvant is an ingredient added to a vaccine that helps create a stronger immune response to vaccination.

What is MF59?

MF59 is an oil-in-water emulsion of squalene oil. Squalene, a naturally occurring substance found in humans, animals and plants, is highly purified for the vaccine manufacturing process. FLUAD™ is approved for use among people 65 years and older, who often have a lower protective immune response after flu vaccination compared to younger, healthier people.

Why are adjuvants added to flu vaccines?

Adjuvants can be added vaccines to enhance immune response. Adjuvants also can reduce the amount of virus needed for production of a vaccine, which can allow for greater supplies of vaccine to be manufactured.

Is FLUAD™ approved in other countries, besides the U.S.?

Yes, FLUAD™ was initially approved in Italy in 1997, and at the time of its U.S. approval in November 2015, had been licensed in 38 countries, including Canada and 15 European countries.

Is everyone approved to receive FLUAD™?

No, FLUAD™ is only licensed and approved for persons aged 65 years and older. FLUAD™ is not recommended for persons with a history of severe allergic reaction to the vaccine or to components other than eggs. Information about vaccine components is located in package inserts from each manufacturer.

Are there increased benefits of FLUAD™ compared to unadjuvanted seasonal flu vaccines for this age group?

Studies that have tested Fluad’s ability to generate an immune response against an influenza virus (immunogenicity) have found that antibody levels were comparable to levels induced by unadjuvanted trivalent seasonal flu vaccines (e.g., Agriflu).  However, an observational study conducted in Canada among adults 65 years of age and older during the 2011-2012 flu season found that FLUAD™ was significantly more effective in preventing laboratory-confirmed influenza compared with an unadjuvanted standard-dose inactivated influenza vaccine.

Does FLUAD™ offer better protection than the high-dose flu vaccine?

To date, there have been no randomized studies comparing FLUAD™ with Fluzone High-Dose vaccine.

How safe is FLUAD™?

Some adverse events (which are also reported after regular flu vaccines) were reported more frequently after vaccination with FLUAD™. The most common adverse events experienced during clinical studies were mild to moderate and were temporary, and included pain, redness at the injection site, headache, muscle aches, and malaise.

What other flu vaccines are available for people in this age group?

Previously, people 65 years and older had two flu shots available: A regular dose flu vaccine and a flu vaccine designed specifically for people 65 and older with a higher dose. The high dose vaccine contains four times the amount of antigen as the regular flu shot and has been associated with a stronger immune response following vaccination and better effectiveness than the regular dose flu vaccine in older people. Based on new CDC and Advisory Committee on Immunization Practices (ACIP) recommendations, FLUAD™ is now an acceptable alternative to other vaccines licensed for people 65 and older. There is no preferential recommendation made for any flu vaccine formulation for this age group.

Why is there a need for new flu vaccines designed specifically for people 65 years of age and older?

CDC studies conducted during previous flu seasons estimate that 80 to 90 percent of seasonal flu-related deaths and 50-70 percent of hospitalizations occur among people 65 years of age and older. However, older adults with weaker immune systems also may have a lower protective immune response after flu vaccination compared to younger, healthier people. This can result in lower vaccine effectiveness (i.e., a measure of how well the flu vaccine protects against flu illness), in these people. Newer flu vaccines made specifically for people 65 years of age attempt to improve the immune response and protection provided by flu vaccination in this age group.

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