The obvious purpose of this
approach is to establish anti HIV reservoirs in the leg muscles of individuals
most at risk to been infected in the first place and that clearly means members
of the sex trade industry in Africa in particular.
Where the disease is endemic,
such a practice would largely halt the production of new victims and perhaps
even protect the workers.
In fact it would jump start the
final eradication of the disease.
It is promising and it appears to
also be a safe approach.
Gene therapy turns muscles into HIV antibody factories
NOVEMBER 30, 2011
David Baltimore of the California Institute of Technology in
Pasadena,California, and colleagues have a new approach that is part
vaccine, part gene therapy. They turn muscles into factories that churn out
potent antibodies against HIV. Because muscle isn't on HIV's hitlist, it will
continue to generate antibodies even after an HIV infection, making the
strategy potentially better than one which tweaks the immune system to produce
the antibodies.
Genetically altered mice were able to resist 100 times the level of HIV that would normally cause an infection.
Nature - Antibody-based protection against HIV infection by vectored immunoprophylaxis
"We produce a similar effect to a vaccine, but without ever calling on the immune system to do any of the work," says Alejandro Balazs, a member of
The team loaded a harmless, cold-related virus called adeno-associated virus (AAV) with genes that make potent antibodies to HIV. Then they used them to "infect" the leg muscles of mice with genes that pump out the antibodies.
"The idea here is to basically supply the body with its own factory for making anti-HIV antibodies," says
The mice continued to make the antibodies throughout their lives, and stayed healthy despite the researchers' best efforts to overwhelm them with HIV.
"We expected that at some dose, the antibodies would fail to protect the mice, but there was no infection even when we gave mice 100 times more HIV than would be needed to infect seven out of eight mice," says Balaz
Despite tremendous efforts, development of an effective vaccine against
human immunodeficiency virus (HIV) has proved an elusive goal. Recently,
however, numerous antibodies have been identified that are capable of
neutralizing most circulating HIV strains. These antibodies all exhibit an
unusually high level of somatic mutation presumably owing to extensive affinity
maturation over the course of continuous exposure to an evolving antigen. Although
substantial effort has focused on the design of immunogens capable of eliciting
antibodies de novo that would target similar epitopes it remains uncertain
whether a conventional vaccine will be able to elicit analogues of the existing
broadly neutralizing antibodies. As an alternative to immunization,
vector-mediated gene transfer could be used to engineer secretion of the
existing broadly neutralizing antibodies into the circulation. Here we describe
a practical implementation of this approach, which we call vectored
immunoprophylaxis (VIP), which in mice induces lifelong expression of these
monoclonal antibodies at high concentrations from a single intramuscular
injection. This is achieved using a specialized adeno-associated virus vector
optimized for the production of full-length antibody from muscle tissue. We
show that humanized mice receiving VIP appear to be fully protected from HIV
infection, even when challenged intravenously with very high doses of
replication-competent virus. Our results suggest that successful translation of
this approach to humans may produce effective prophylaxis against HIV.
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