pEpitone Model Forecasts Flu Shot Will Be 19% Effective For 2018

Mutations in two amino acids in one key region of the hemagglutinin protein lowered vaccine efficacy to 19 percent against all circulating flu strains

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According to a Rice University modeling method the flu vaccine efficacy for the 2018/2019 season will be similar to last year.

Which is not good news.

The pEpitope model predicts that Fall 2018’s flu vaccine, which is a new H3N2 formulation, will likely have the same limited efficacy against the dominant circulating strain of influenza A.

This sub-standard efficacy is due to viral mutations related to vaccine production in eggs.

The Rice method, known as pEpitope, is a computational method that measures critical differences in the genetic sequences of flu strains.

pEitope was invented more than 10 years ago as a fast, inexpensive way of gauging the effectiveness of proposed flu vaccine formulations. The pEpitope method accounts for 77 percent of what impacts efficacy of the vaccine in humans.

The latest pEpitope study, which is published in Clinical Infectious Diseases, suggests pEpitope is a more accurate predictor of vaccine efficacy than long-relied-upon ferret tests.

“The flu vaccine for 2018/19 has changed, 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.”

Most flu vaccines are produced with a decades-old process that involves culturing viruses in hundreds of millions of chicken eggs.

Because the strain of flu that infects people is often difficult to grow in eggs, vaccine producers must make compromises to produce enough egg-based vaccine in time for fall flu shots.

Unintended effects of this process have reduced vaccine efficacy against H3N2 the past two years, Deem said.

“Very often there are egg adaptations,” he said. “There were a couple of these in the vaccine strain the past two seasons that wound up making it a little bit different from the actual circulating virus strain.”

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Deem and Melia Bonomo used the pEpitope method to rapidly calculate how much the egg-passage mutations would decrease vaccine efficacy in humans.

“In fact, it’s pretty substantial,” said Bonomo, a doctoral student in applied physics.

“The original strain used as a reference for the vaccine was basically a perfect match to the dominant circulating strain, and the predicted efficacy would have been around 47 percent.”

“We found that the mutations in two amino acids out of more than 300 in one key region of the hemagglutinin protein were enough to lower efficacy to 19 percent against all circulating strains.”

He and Bonomo compared the efficacy of the egg-based vaccine with an experimental vaccine produced from insect cells via reverse genetics.

The cell-based vaccine, which did not have the egg-passage mutations, had a predicted efficacy of 47 percent, the average value of a perfectly matched H3N2 vaccine, Deem said.

For decades, scientists have relied upon ferret models to gauge how flu viruses and flu vaccines will behave in people.

But, Deem said ferret studies over the past 10 years have been considerably less predictive of human effects than they were in the preceding three decades, and it is unclear why.

Deem said the ferret-based measures are one-third as predictive as the pEpitope method that has consistent performance over decades of flu data.

“When we look at our model overall data and over the last 10 years, we get the same answer,” Deem said.

“Whether we use the last 10 years of data or the last 50 years, our theory is very robust.”

The research was funded by the National Science Foundation via Rice’s Center for Theoretical Biological Physics and by the Welch Foundation.