Friday, February 06, 2015

Revisiting CIDRAP’s - The Need For Better Flu Vaccines



# 9780


There’s an accusatory headline, and article, in the UK’s Telegraph today (see Flu vaccine: Ministers may have known of dangerous new strain last March), strongly suggesting that the World Health Organization and other public health entities (including the UK’s PHE) somehow bungled this year’s flu vaccine by not including the new `drifted’ strain’.


I guess anytime you can blame the government,  it plays well in Portsmouth, and sells papers.


A far more reasonable report can be found on the BBC website, called Why flu vaccines are underperforming this winter, which essentially attributes this year’s vaccine fiasco to `bad luck’.


The cause of this consternation is the Eurosurveillance journal report, released yesterday, that calculated an abysmal 3.4% VE (Vaccine Effectiveness) rating for this year’s jab, down from the 50%-60% we normally see.  The inevitable result of this type of vaccine mismatch is a commensurate jump in the number of `excess winter deaths’ – primarily among the elderly.

The problem is, as it has been for more than a half century, that it takes roughly 6 months to produce, prepare, and ship hundreds of millions of doses of flu vaccine, and so the strains to be included must be selected very early in the spring if the vaccine is to be ready by fall.

Complicating matters, while we talk about 2 primary influenza A subtypes (H1N1 & H3N2), in truth there are multiple variations on each in circulation at any given time.   Usually, one of these versions – or clades – dominates over all of the others, but they are constantly playing a viral game of `king of the mountain’, and the balance of power can shift quickly.


The change that the Ministers `knew’ about a new strain last March holds little sway when you look back at the Influenza Virus Characterization reports from the ECDC from last spring and summer that described multiple H3N2 variants.


While a few of the viruses tested were antigenically different from the vaccine strain, the majority were still a match.


Influenza Virus Characterisation, May 2014

  • Recently circulating A(H3N2) viruses have fallen within genetic group 3C represented by the recommended vaccine virus for the 2013–14 and 2014–15 seasons, A/Texas/50/2012, with viruses of genetic subgroup 3C.3 predominating. Antigenic analysis using antisera raised against cell-propagated H3N2 viruses indicates that the majority of circulating viruses are antigenically similar to those in circulation in the 2012–13 and 2013–14 influenza seasons.
  • A small set of viruses in genetic subgroup 3C.3 were not recognised well by the panel of antisera and their HA gene sequences encode several amino acid substitutions compared to other viruses in genetic group 3C.3.

At this point, the components of this year’s vaccine had been `locked in’ for a couple of months, and it was really too late to change. And at this point, it wasn’t at all clear which strain would dominate come the fall.  By September (see ECDC’s Influenza virus characterisation, Summary Europe, September 2014), it was becoming apparent that this new subset of antigenic viruses were on the ascendant, and that report included:

In light of the emergence of antigenically distinct groups of influenza A(H3N2) and the altered
prevalence of influenza B viruses, the WHO recommended composition of influenza vaccines for use in the 2015 southern hemisphere influenza season differed from that recommended for use in the 2014–15 northern hemisphere influenza season.


In early November, when I wrote A `Drift’ In A Sea Of Influenza Viruses,  the CDC was still reporting 70% of the  H3N2 viruses tested matched the vaccine component.  Since then, those numbers have fallen to 35% or so.  In Canada, and apparently in Europe as well, those numbers are even lower still.

Twice each year, a group of distinguished influenza scientists gather to try to predict what seasonal flu viruses dominate in six month’s time. 


And this year, quite frankly, they guessed wrong.  It happens.  No one has a crystal ball.

One of the big obstacles, of course, is vaccine production time. If vaccine strains could be picked in June or July, and the vaccine produced in 60 days, we’d far see fewer vaccine mismatches.  And that would allow for the timely creation, production, and distribution of an emergency pandemic vaccine as well.


But despite a good deal of research, most influenza vaccines are still produced using (admittedly updated) 1950s egg-based technologies.

More than three two years ago, in CIDRAP: The Need For `Game Changing’ Flu Vaccines, we looked at major report – serving as a clarion call for a revolution in vaccine technology - that is as relevant today as the day it was published.


Since reports like this one tend to make a big splash, and then are all too quickly forgotten, today seems a good day to revisit that study.


The Compelling Need for Game-Changing Influenza Vaccines

An Analysis of the Influenza Vaccine Enterprise and Recommendations for the Future

Michael T. Osterholm, PhD, MPH, Nicholas S. Kelley, PhD, Jill M. Manske, PhD, MPH, Katie S. Ballering, PhD, Tabitha R. Leighton, MPH, Kristine A. Moore, MD, MPH


For those not ready to commit to reading a 160-page report, there is a 12-page Executive summary available.


At this point I’ll turn to the press release from CIDRAP, where Dr. Osterholm emphasizes the idea that our history of overestimating the effectiveness of the current vaccine serves as a barrier to developing new vaccine technologies.  A bias that perhaps this year, will change.


New U of M-led analysis finds urgent need for new influenza vaccines

Laurel Herold, Academic Health Center, 612-624-2449,
Justin Paquette, Academic Health Center, 612-626-7037,

MINNEAPOLIS/ST. PAUL (October 15, 2012) – According to a new report from the University of Minnesota’s Center for Infectious Disease Research and Policy (CIDRAP), current influenza vaccines offer less protection against seasonal influenza than previously reported. As a result, the misperception that current vaccines are highly effective in fighting influenza has become a barrier to creating new, more effective vaccines.


“We urge people to get their flu shot. The present vaccines are the best interventions available for seasonal influenza,” said Michael T. Osterholm, Ph.D., M.P.H., University of Minnesota infectious disease expert and the CCIVI report’s lead author. “However, these vaccines do not offer consistent, high-level protection – especially in individuals at risk of medical complications or those aged older than 65 years. Unfortunately, these are the populations where we need the vaccines to work the best.  We need new influenza vaccines that work for everyone, most of the time.”

Researchers found that during some influenza seasons, current vaccines offer more protection for most of the population than being unvaccinated. However, compared to most routinely recommended vaccines, influenza vaccine protection is substantially lower.

“We can no longer accept the status quo with regard to influenza vaccine research and development,” added CCIVI expert advisory group chair, Alfred Sommer, Ph.D, Johns Hopkins Bloomberg School of Public Health, after reviewing the latest report. “Only with new game-changing vaccines can we ever really be prepared for the next influenza pandemic.”

(Continue . . .)


Despite its limitations, I get the flu vaccine each year, and continue to recommend that others take it as well.  Not because I view it as perfect, or even very good.  At best, it provides a moderate level of protection against the flu – at worst . . . . well, all you have to do is look at this year’s FluView reports.

But however flawed, flu vaccines remain our best protection against a virus that is estimated to kill a half million people around the globe each year. 


Like wearing a seatbelt cannot guarantee you’ll walk away from a head-on collision,  a flu vaccine cannot guarantee you won’t get the flu this year.


But most years, it reduces your odds of a bad outcome by about half.  And until something better comes along, you use what you can to your best advantage.

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