Friday, April 20, 2018

C.I.D.: Predicting Influenza H3N2 Vaccine Efficacy from Evolution of the Dominant Epitope


After this past winter's severe H3N2 flu season, which was aided and abetted by a seriously disappointing H3N2 component to the seasonal flu vaccine, the last thing anyone wants to see are the headlines from yesterday forecasting another poor vaccine performance this fall.
Rice University study suggests 2018 flu vaccine will have 20 percent success rate -
Rice University study suggests 2018 flu vaccine will have 20 percent success rate - CW39
Fall 2018 flu vaccine will be 20 percent effective, study predicts -UPI
April 19 (UPI) -- This fall's flu vaccine will be 20 percent effective for the dominant circulating strain of influenza A, the same as shots given the past two years, a new study predicts.
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Admittedly, not exactly the message that public health officials want to see splashed all over the media during the run up to next fall's vaccination campaign (or for the Southern Hemisphere's campaign right now).
While the performance of next fall's H3N2 vaccine component - which suffers from mutations generated during its passage through eggs (see PLoS Path.: A Structural Explanation For The Low VE Of Recent H3N2 Vaccines) - seems likely fall short again next fall, that is (thankfully) not the whole story.  
We've had two H3N2 dominant flu seasons in a row.  While it is certainly possible we'll be unlucky enough to see a third, right now H1N1 appears to be picking up steam around the globe, and we may see it become the dominant strain next fall (see WHO Update below)

62.7% of Influenza A  H1N1 / 37.3% H3N2

Although H1N1 cases were few and far between this past winter, the CDC's Interim Vaccine Effectiveness numbers (released in Feb) estimated a 67% (CI = 54%–76%) VE against A(H1N1)pdm09 viruses.
Even assuming that proves optimistic due to the small sample size, the VE against H1N1 has generally run over 50%.
Which means - depending upon the mix of influenza A & B viruses next fall - the vaccine may not prove to be as much of a dud as these headlines would suggest.  Only time will tell.

All of this dire reportage stems from what I'm sure is a fascinating study, published this week in Clinical Infectious Diseases, that is (alas) almost entirely behind a pay wall.  There is not much I can do but provide a link.
Predicting Influenza H3N2 Vaccine Efficacy from Evolution of the Dominant Epitope
Melia E Bonomo Michael W Deem
Clinical Infectious Diseases, ciy323,
Published: 17 April 2018


We predict vaccine efficacy with a measure of antigenic distance between influenza A(H3N2) and candidate vaccine viruses based on amino acid substitutions in the dominant epitopes. In 2016-2017, our model predicts 19% efficacy compared to 20% observed. This tool assists candidate vaccine selection by predicting human protection against circulating strains.
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What we do have is a press release (below) from Rice University, which provides some pretty good background on the study.  It too, glosses over the possibility that next year could be an H1N1 dominant year, which undoubtedly explains the media's slant.
Study predicts 2018 flu vaccine will have 20 percent efficacy
Jade Boyd – April 19, 2018 David Ruth


Jade Boyd

Study predicts 2018 flu vaccine will have 20 percent efficacy
Rice U. study finds egg adaptations will limit efficacy of new flu vaccine

HOUSTON — (April 19, 2018) — A Rice University study predicts that this fall’s flu vaccine — a new H3N2 formulation for the first time since 2015 — will likely have the same reduced efficacy against the dominant circulating strain of influenza A as the vaccine given in 2016 and 2017 due to viral mutations related to vaccine production in eggs.

The Rice method, known as pEpitope (pronounced PEE-epih-tope), was invented more than 10 years ago as a fast, inexpensive way of gauging the effectiveness of proposed flu vaccine formulations. The latest pEpitope study, which is available online this week in Clinical Infectious Diseases, suggests pEpitope is a more accurate predictor of vaccine efficacy than long-relied-upon ferret tests, particularly for data gathered in the past decade. The pEpitope method accounts for 77 percent of what impacts efficacy of the vaccine in humans.

pEpitope is a computational method that measures critical differences in the genetic sequences of flu strains. In the new study, the method accurately predicted vaccine efficacy rates for more than 40 years of flu records. These included the past two flu seasons in which vaccines offered only limited protection against the most widely circulating strain of influenza A.

“The vaccine has been changed for 2018-19, but unfortunately it still contains two critical mutations that arise from the egg-based vaccine production process,” said Michael Deem, Rice’s John W. Cox Professor in Biochemical and Genetic Engineering and professor of physics and astronomy. “Our study found that these same mutations halved the efficacy of flu vaccines in the past two seasons, and we expect they will lower the efficacy of the next vaccine in a similar manner.”

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As I said, this appears to be a fascinating project, and I look forward to seeing more on it.  And until we change the way flu vaccines are produced, it is very likely - particularly with H3N2 - that these VE problems will continue.

By the middle of last summer it was becoming apparent that the 2017-18 H3N2 vaccine component was likely to be `suboptimal' once again (see The Enigmatic, Problematic H3N2 Influenza Virus) and the prospects of a another H3N2 dominated North America flu season were looking pretty good.  
Despite those warning signs, I got the flu vaccine last September and urged others to do so as well, figuring that some protection beats no protection at all.   
While this year's flu vaccine was far less effective than we'd like, the CDC's mid-season estimate of the overall U.S. VE (Vaccine Effectiveness) against both A & B subtypes was 36%. Some age groups however - notably adolescents (9-17), and adults 50 and older - showed no statistically significant protection from the vaccine.
One bright spot is that kids aged 6 months through 8 years saw as much as 59% protection from this year's vaccine.  And in a year where we've seen more than 150 flu-related pediatric deaths, without the vaccine, that number would undoubtedly have been higher.
Although I think the benefits of the flu vaccine are sometimes oversold, it does have genuine value, even in years when its VE is sub-par. A few recent studies showing this include:
CMAJ Research: Repeated Flu Vaccinations Reduce Severity of Illness In Elderly
CID Journal: Flu Vaccine Reduces Severe Outcomes in Hospitalized Patients
More Evidence Flu Shots May Improve Outcomes In Critical Patients
Study: Flu Vaccine May Reduce Heart Attack Risk
Despite being far from perfect, the flu vaccine – along with practicing good flu hygiene (washing hands, covering coughs, & staying home if sick) – still remains your best strategy for avoiding the flu and staying healthy this winter.

Regardless of what the headlines say.

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