CMV
Vaccine Clears SIV in Monkeys
SUMMARY
Macaques given a CMV vector vaccine showed sustained CD8
T-cell activation, which was associated with control of
a virus related to HIV. |
As
reported in the May
11, 2011, advance online edition of Nature, investigators
tested a vaccine designed to protect against simian immunodeficiency
virus (SIV), a relative of HIV that infects non-human primates.
The
vaccine, consisting of SIV antigens combined with a cytomegalovirus
(CMV) vector, stimulated an ongoing memory T-cell immune response,
which appeared to inhibit mucosal SIV infection at the earliest
stages. Nearly half of the macaques that received the CMV
vaccine either alone or followed by an adenovirus vector vaccine
demonstrated "early complete control" of SIV; 12
of these 13 monkeys showed protection lasting at least 1 year.
Below
is an edited excerpt from a press release issued by Oregon
Health and Science University explaining the research and
its findings.
Non-Human
Primate Studies Reveal
Promising Vaccine Approach for HIV
Hillsboro,
OR -- May 11, 2011 -- Research conducted at Oregon Health
and Science University's Vaccine and Gene Therapy Institute
(VGTI) has developed a vaccine candidate in non-human primates
that may eventually lead to a vaccine against Human Immunodeficiency
Virus (HIV). Details of this advance are published in the
advance online edition of the journal Nature. The paper
will also be published in an upcoming print addition of the
journal.
The research team, led by Louis Picker, MD, associate director
of the OHSU VGTI and director of the VGTI's vaccine program,
produced a vaccine candidate that programs the immune system
of non-human primates to respond more swiftly to the presence
of a primate version of HIV than it normally would. The team
also included researchers from the National Cancer Institute-Frederick
and the International AIDS Vaccine Initiative.
The VGTI researchers tested their vaccine candidate in rhesus
macaque monkeys at the Oregon National Primate Research Center
using a monkey form of HIV called Simian Immunodeficiency
Virus (SIV). Of the monkeys that received the vaccine candidate,
just more than half controlled replication of the virus to
the extent that even the most sensitive tests could not detect
signs of SIV.
To date, the vast majority of these animals have maintained
control over the virus for more than a year, gradually losing
any signs that they had ever been infected. In contrast, the
macaques in the unvaccinated control group developed the monkey
form of AIDS.
The researchers say that their work suggests that the immune
responses elicited by this new vaccine candidate might completely
clear SIV from animals that were initially infected. In comparison,
antiretroviral therapy is able to control the disease, but
cannot clear the virus from its hiding place within the immune
systems own cells.
The VGTI team has been working for over ten years on its vaccine
candidate, which is unique in using cytomegalovirus (CMV)
as the transport system used to introduce the vaccine into
the body. CMV was chosen because it is believed that most
people are already infected with CMV, but for the majority,
the virus causes little or no symptoms. In addition, once
a person is infected with CMV, this virus remains in the body
for life. Picker and his team hypothesized that if such a
persistent virus were used as a vector it could create and
maintain resistance against HIV by programming a portion of
the body's immune system called effector memory T-cells to
be constantly on the alert for the virus.
"The next step in vaccine development is to test the
vaccine candidate in clinical trials in humans. For a human
vaccine the CMV vector would be weakened sufficiently so that
it does not cause illness, but will still protect against
HIV," said Dr. Picker.
Investigator affiliations: Vaccine and Gene Therapy Institute,
Departments of Molecular Microbiology and Immunology and Pathology,
and the Oregon National Primate Research Center, Oregon Health
& Science University, Beaverton, OR; AIDS and Cancer Virus
Program, SAIC Frederick Inc., National Cancer Institute-Frederick,
Frederick, MD; International AIDS Vaccine Initiative, Vaccine
Design and Development Laboratory, Brooklyn, NY. The National
Institutes of Health and, the International AIDS Vaccine Initiative
provided funding for this research.
5/17/11
Reference
SG Hansen, JC Ford, MS Lewis, et al. Profound early control
of highly pathogenic SIV by an effector memory T-cell vaccine.
Nature (abstract).
May 11, 2011 (Epub ahead of print).
Other
Source
Oregon
Health & Science University. Non-Human Primate Studies
Reveal Promising Vaccine Approach for HIV. Press release.
May 11, 2011.
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