A
new way to create proteins that can sneak through HIV's protective coating may
be a step toward understanding the key components needed for developing a
vaccine for the virus, according to researchers.
Using
computational modeling, a team of researchers led by Penn State
designed and created proteins that mimicked different surface features of HIV.
After being immunized with the proteins, rabbits developed antibodies that were
able to bind with the virus.
Zhu
added that the study provides a novel way to design proteins for vaccines.
"The
proteins -- or immunogens -- we developed aren't a finished product, but we
were able to show evidence that it's possible to do," Zhu said.
"Moreover, it's also very exciting that we were able to create a new
method to tailor make proteins, which could open the door for developing
vaccines for other infections, as well."
"Even
if we develop an antibody for a particular strain of the virus, that antibody
may not even notice the next strain of the virus," Dokholyan said.
"In order to develop broadly neutralizing antibodies -- antibodies that
neutralize multiple strains of a virus -- we need to find something that
remains constant on the virus for those antibodies to latch onto."
According
to Dokholyan, HIV uses a coating of carbohydrates to protect a protein on its
surface called Env. While this protein could be a potential target for
vaccines, the carbohydrate coating makes it difficult or impossible for
antibodies to access and neutralize it.
But
sometimes, holes naturally appear in this coating, exposing the Env protein to
potential antibodies. Zhu said he and the other researchers wanted to find a
way to target these holes.
"The
idea would be to do molecular surgery to copy sections of the virus's surface
and paste them onto different, benign proteins, so they would look but not act
like the Env protein," Zhu said. "Hopefully, this would allow the
immune system to recognize the virus and create antibodies to neutralize it in
the future."
The
researchers used computational models to design proteins that would mimic the
conserved protein surface of different strains of HIV to be used in the
vaccine. Dokholyan said that while usually proteins are engineered by changing
one amino acid at a time, they wanted to try a different approach.
"Instead
of changing one amino acid at a time, it's a large surface of the HIV strain
that is cut and then plugged onto a different protein," Dokholyan said.
"It's an important milestone be able to do these major molecular
surgeries, and it's very exciting that the strategy worked with a very high
accuracy."
The
researchers said that while the findings are promising, there is still more
work to be done.
"It's
important that we were able to generate an immune response to HIV and show that
it's possible as a proof of concept," Dokholyan said. "But, we still
need to improve the antibodies' neutralization abilities and other aspects
before it can become a viable vaccine."
Dokholyan
said that in the future, the protein design method could potentially help
create and personalize vaccines for different diseases in various areas in the
world.
"Diseases
can vary by location, for example, there are different strains of HIV in
various countries or regions," Dokholyan said. "If we can easily
customize proteins for vaccines, that's a good example of where personalized
medicine is going to play a role."
The
National Institutes of Health helped support this research.
See:
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology
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