The L194P egg-adaptive mutation
dramatically increases the motility of the major epitope on the
hemagglutinin of influenza H3 viruses. Red: high motility; white: medium
motility; blue: low motility.
Credit: Wilson Lab
According to a new study from
scientists at The Scripps Research Institute (TSRI), the common practice
of growing influenza vaccine components in chicken eggs disrupts the
major antibody target site on the virus surface, rendering the flu
vaccine less effective in humans.
"Now we can explain -- at an atomic level -- why egg-based vaccine
production is causing problems," said TSRI Research Associate Nicholas
Wu, Ph.D., first author of the study, published recently in the journal PLOS Pathogens.
For more than 70 years, manufacturers have made the flu vaccine by
injecting influenza into chicken eggs, allowing the virus to replicate
inside the eggs and then purifying the fluid from the eggs to get enough
of the virus to use in vaccines.
The subtype of influenza in this study, called H3N2, is one of
several subtypes shown to mutate when grown in chicken eggs, and the
researchers say the new findings further support the case for
alternative approaches to growing the virus.
"Any influenza viruses produced in eggs have to adapt to growing in
that environment and hence generate mutations to grow better," explained
study senior author Ian Wilson, D.Phil., Hansen Professor of Structural
Biology at TSRI.
The new study shows exactly why egg-based manufacturing is a problem
for the H3N2 subtype. As H3N2 influenza has become more prevalent,
scientists formulating the seasonal flu vaccine have sought to include
this virus and teach the human immune system to fight it. Despite this
effort, recent flu vaccines have proven only 33 percent effective
against H3N2 viruses.
Wu used a high-resolution imaging technique called X-ray
crystallography to show that -- when grown in eggs -- the H3N2 subtype
mutates a key protein to better attach to receptors in bird cells.
Specifically, there was a mutation called L194P on the virus's
hemagglutinin glycoprotein (HA). This mutation disrupts the region on
the protein that is commonly recognized by our immune system.
This means a vaccine containing the mutated version of the protein
will not be able to trigger an effective immune response. This leaves
the body without protection against circulating strains of H3N2.
In fact, Wu's analysis shows that the current strain of H3N2 used in
vaccines already contains this specific mutation L194P on HA. "Vaccine
producers need to look at this mutation," cautioned Wu.
The researchers say further studies are needed to investigate
replacing the egg-based system. "Other methods are now being used and
explored for production of vaccines in mammalian cells using cell-based
methods and recombinant HA protein vaccines," said Wilson.
"There's a huge need for flu vaccine research," added Wu.
Story Source:
http://www.scripps.edu/news/press/2017/20171030wilson.html" rel="nofollow - Materials provided by http://www.scripps.edu" rel="nofollow - Scripps Research Institute . Note: Content may be edited for style and length.