Three antibodies combined into one protected monkeys against a simian version of HIV, opening the door for human trials.
September 25, 2017
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Researchers have reached an important milestone in the long-range
effort to harness the power of so-called broadly neutralizing antibodies
against HIV for use as treatment and prevention of the virus.
Experiments in monkeys found that synthesizing three such antibodies
into one protected the primates against exposure to SHIV, a simian
version of HIV developed for research purposes.
Compared
with individual antibodies, the “trispecific” antibody, which contains
three prongs, each of which affects a different site on the surface, or
envelope, of HIV, proved superior in thwarting the virus in the test
animals. This finding suggests that, just as with standard
antiretroviral (ARV) treatment, a combination-therapy approach will
prove the most potent and put up the highest barrier against resistant
virus.
Publishing their findings in the journal
Science, National Institutes of Health (NIH) researchers, working in
partnership with the Paris-based pharmaceutical company Sanofi,
conducted extensive laboratory tests to identify the most promising
double or triple combinations of antibodies. They used Sanofi’s
technology to combine these antibodies into single, multipronged
antibodies. Ultimately, they found that the combination that best
attacked HIV included the antibodies VRC01, PGDM1400 and 10E8v4.
Scientists are currently investigating VRC01
in a pair of large, multiyear Phase III clinical trials to determine
its efficacy as pre-exposure prophylaxis (PrEP) against HIV when infused
every eight weeks.
The researchers in the trispecific
antibody study infused eight macaque monkeys with VRC01, eight monkeys
with PGDM1400 and eight monkeys with the triple-pronged antibody. Five
days later, they exposed all the monkeys to two strains of SHIV. One
strain of the virus was vulnerable to attack by VRC01 and the
trispecific antibody but resistant to PGDM1400, while the other strain
was vulnerable to attack by PGDM1400 and the trispecific antibody but
resistant to VRC01.
Five of the eight monkeys (62.5
percent) that received PGDM1400 and six of the eight (75 percent) that
received VRC01 became infected with SHIV. None of the animals that
received the trispecific antibody were infected.
Sanofi
and the National Institute for Allergies and Infectious Diseases
(NIAID), a division of the NIH, are gearing up for a Phase I human trial
of the trispecific antibody to begin in 2018. The trial will test the
antibody’s safety and how it is metabolized in HIV-negative individuals.
NIAID is also looking into launching another Phase I trial of the
trispecific antibody among HIV-positive individuals.
Scientists
hope that successful clinical trials—there are three main phases before
a new treatment may receive approval from the Food and Drug
Administration—may yield a new way to treat and prevent the virus, with
intermittent infusions of antibodies.
The study authors
believe that this method of combining antibodies could also lead to new
treatments for infectious diseases other than HIV, as well as
autoimmune diseases and cancers.
To read the study abstract, click here.
To read a press release about the study, click here.
Read more articles from POZ, here.
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