Researchers have developed a drug which may lead to HIV vaccine

Scientists have developed a novel
drug that may lead to a universally effective HIV vaccine. When tested in
monkeys the vaccine blocked every strain of HIV and protected them for eight
months. In a remarkable new advance against the virus that causes AIDS,
scientists from The Scripps Research Institute (TSRI) have announced the
creation of a novel drug candidate that is so potent and universally effective;
it might work as part of an unconventional vaccine.

The research, which involved
scientists from more than a dozen research institutions and both campuses of
TSRI, was published in the journal Nature. The study shows that the new drug
candidate blocks every strain of HIV-1, HIV-2 and SIV (simian immunodeficiency
virus) that has been isolated from humans or rhesus macaques, including the
hardest-to-stop variants. It also the hardest-to-stop variants. It also
protects against much-higher doses of virus than occur in most human
transmission and does so for at least eight months after injection. “Our compound
is the broadest and most potent entry inhibitor described so far,” said Michael
Farzan, who led the effort. “Unlike antibodies, which fail to neutralize a
large fraction of HIV-1 strains, our protein has been effective against all
strains tested, raising the possibility it could offer an effective HIV vaccine

Lead author Michael Farzan,
right, with Matthew Gardner in Dr. Farzan’s lab at the Scripps Research
Institute on Wednesday. (Photo credit: ROLANDO DIAZ FOR THE WALL STREET JOURNAL)

When HIV infects a cell, it
targets the CD4 lymphocyte, an integral part of the body’s immune system. HIV
fuses with the cell and inserts its own genetic material ­ in this case, single
stranded RNA ­ and transforms the host cell into a HIV manufacturing site. The
new study builds on previous discoveries by the Farzan laboratory; which show
that a co-receptor called CCR5 contains unusual modifications in its critical
HIV-binding region, and that proteins based on this region can be used to
prevent infection. With this knowledge, Farzan and his team developed the new
drug candidate so that it binds to two sites on the surface of the virus
simultaneously, preventing entry of HIV into the host cell.

“When antibodies try to mimic the
receptor, they touch a lot of other parts of the viral envelope that HIV can
change with ease,” said Matthew Gardner, who is the first author of the study
with Lisa Kattenhorn. “We’ve developed a direct mimic of the receptors without
providing many avenues that the virus can use to escape, so we catch every
virus thus far.” The team also leveraged preexisting technology in designing a
delivery vehicle ­ an engineered adeno-associated virus, a small, relatively
innocuous virus that causes no disease. Once injected into muscle tissue, like
HIV itself, the vehicle turns those cells into “factories” that could produce
enough of the new protective protein to last for years, perhaps decades, Farzan

Data from the new study showed
the drug candidate binds to the envelope of HIV-1 more potently than the best
broadly neutralizing antibodies against the virus. Also, when macaque models
were inoculated with the drug candidate, they were protected from multiple
challenges by SIV. “This is the culmination of more than a decade’s worth of
work on the biochemistry of how HIV enters cells,” Farzan said. “When we did
our original work on CCR5, people thought it was interesting, but no one saw
the therapeutic potential. That potential is starting to be realized.”


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