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Preparing for Influenza: An H3N2 Season with a Vaccine Mismatch

Amesh A. Adalja, MD, FACP, FACEP, December 19, 2014

As this year’s flu season begins to pick up speed, early indicators point to a particularly severe season. Thus far, flu activity has not been widespread across most of the nation, but several southern states have been reporting high rates of influenza, and as we approach the traditional peak of flu activity (February), the nation will follow suit. Thus far, 7 pediatric deaths have been reported.1


Flu Vaccine Mismatch

One factor that will likely play a major role in the severity of the season is the mismatch of the H3N2 component of the now quadrivalent vaccine. This season the dominant H3N2 virus is a “drift” variant from the vaccine strain—a phenomenon that happens from time to time. This is ominous because H3N2 is the dominant strain so far this year. 

In the week ending December 6, 2014, the CDC reported that, of subtype flu A viruses, all but 7 A isolates were H3N2 and virtually all of these were the drift variant. There has been almost no H1N1 this year, and influenza B has been responsible for only 4.8% of flu cases this season.1


H3N2 Seasons

H3N2-dominant seasons tend to be more severe than seasons dominated by other strains and are characterized by a particular predilection to attack the very young and the very old, the populations at highest risk for severe influenza.2 Because of the mismatch of the vaccine this season, the chief means to prevent complications from influenza will be the use of neuraminidase inhibitors. Adamantane drugs (such as rimantadine) should be avoided because of high rates of resistance to them among circulating flu viruses of all types. Clinicians must promptly prescribe either oseltamivir or zanamivir to those suspected of having influenza. However, in those with delayed presentations or diagnosis, antiviral therapy will likely still have benefit (as shown in retrospective analyses).3

Although the vaccine being employed for the upcoming season in the southern hemisphere will include the new H3N2 variant, the fact that another mismatched season has occurred, despite the development of a quadrivalent vaccine, underscores the need for a game-changing vaccine. Such a vaccine would be directed against a universal antigen of the virus, leaving no room for drift variants to derail it. 



  1. Weekly U.S. influenza surveillance report. Centers for Disease Control and Prevention website. Updated December 12, 2014. Accessed December 16, 2014.
  2. Adalja AA. Comparing severity and outcomes for seasonal and 2009 H1N1 infections. JAMA 2011;305:39-40.
  3. Viasus D, Pano-Pardo JR, Pachon J, et al. Timing of oseltamivir administration and outcomes in hospitalized adults with pandemic 2009 influenza A(H1N1) virus infection. Chest 2011;140:1025-1032.