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[afro-nets] Phase II trial of 'global' HIV/AIDS vaccine

NIAID launches first Phase II trial of a 'global' HIV/AIDS vac-

12 October 2005

A novel vaccine targeted to multiple HIV subtypes found world-
wide has moved into the second phase of clinical testing, the
National Institute of Allergy and Infectious Diseases (NIAID),
part of the National Institutes of Health (NIH), announced to-
day. The study investigators plan to enrol a total of 480 par-
ticipants at sites in Africa, North America, South America and
the Caribbean to test the safety and immune response to the vac-

The experimental vaccine was developed by scientists at NIAID's
Dale and Betty Bumpers Vaccine Research Center (VRC) and is be-
ing studied in the HIV Vaccine Trials Network (HVTN), a clinical
research collaboration funded by NIAID's Division of AIDS

"This trial marks an important step in the advancement toward an
AIDS vaccine. The rapid development of this candidate vaccine--
less than five years since the launch of the VRC--underscores
our commitment to hasten the day when we have an effective AIDS
vaccine," says NIAID Director Anthony S. Fauci, M.D.

The unique vaccine combines synthetically modified elements of
four HIV genes found in subtypes A, B and C of the virus--the
subtypes commonly found in Africa, the Americas, Europe and
parts of Asia. These subtypes represent about 85 percent of HIV
infections worldwide.

"This is the first Phase II study of a vaccine candidate that is
broadly relevant to the global AIDS pandemic because it combines
components of HIV strains found throughout the world," says VRC
Director Gary Nabel, M.D., Ph.D. "We look forward to working
with our partners in the United States and abroad as we take
this vaccine into the next phase of clinical evaluation."

The trial, known as HVTN 204, is being coordinated with two
other planned clinical studies, an unprecedented collaboration
among researchers in three clinical trial networks and NIAID.
The International AIDS Vaccine Initiative plans to conduct a
Phase I study of the VRC vaccine at sites in Kenya and Rwanda,
and the U.S. Military HIV Research Program plans Phase I and II
studies at sites in Uganda, Kenya and Tanzania; the studies are
contingent on the appropriate regulatory and ethical approvals
being granted in these countries.

About the Vaccine

The three harmonized trials will be testing a "prime-boost"
strategy composed of two vaccine components given at different
times. Both contain synthetic versions of four HIV genes: gag,
pol, nef and env. The gag, pol and nef genes come from HIV sub-
type B, the primary virus found in Europe and North America.
Env, the fourth gene, codes for an HIV coat protein that allows
the virus to recognize and attach to human cells. The vaccine
incorporates modified env genes from subtypes A and C, most com-
mon in Africa and parts of Asia, as well as subtype B.

The two vaccine components differ in how the genes are packaged.
One contains only the naked gene fragments, which cannot recon-
stitute into an infectious virus. The other uses a weakened type
of respiratory virus known as adenovirus as a vector to shuttle
the non-infectious gene fragments into the body.

Adenoviruses cause upper respiratory tract illness, such as the
common cold. However, because the vaccine contains only HIV gene
fragments housed in an adenovirus that cannot replicate, study
participants cannot become infected with HIV or get a respira-
tory infection from the vaccine.

"The use of adenovirus vectors appears to be the most promising
advance in recent years in the search for an HIV vaccine," says
Peggy Johnston, Ph.D., director of the Vaccine and Prevention
Research Program in DAIDS, NIAID. Lawrence Corey, M.D., princi-
pal investigator of the HVTN, adds, "We are excited to work with
the VRC on this new vaccine candidate. This prime-boost approach
incorporating adenovirus vector seems to generate the type and
quantity of immune responses we feel will be necessary to impact
an infection like HIV. This study will define more completely
the levels of immunity this novel approach will achieve in a
broad range of people."

The DNA components of the vaccine were manufactured by the San
Diego-based Vical, Inc. The adenovirus vector was developed by
VRC in collaboration with GenVec Inc., of Gaithersburg, Md.,
which also manufactured the adenovirus vector vaccine.

HVTN 204 Study Details

The HVTN 204 Phase II study will test the safety and ability of
the vaccine to generate an immune response in 480 healthy, HIV-
negative adults ages 18 to 50. The researchers plan to recruit
volunteers from populations particularly hard-hit by AIDS, in-
cluding African Americans and other ethnic minorities.

The study is being led by Michael Keefer, M.D., of the Univer-
sity of Rochester, NY, and Gavin Churchyard, M.B.B.Ch., F.C.P.,
M.Med., Ph.D., of Aurum Health Research Ltd. in South Africa.

The trial opened at the University of Alabama at Birmingham and
is designed to include 13 HVTN sites, provided that regulatory
and ethical approval is granted at each site:

* North America--Baltimore, MD; Boston, MA; Providence, RI; Bir-
mingham, AL; Nashville, TN; and Rochester, NY
* South America--Rio de Janeiro and S Paulo, Brazil
* Caribbean--Port-au-Prince, Haiti; Kingston, Jamaica
* Africa--Gaborone, Botswana; and Cape Town, Soweto, and KOSH
(Klerksdorp, Orkney, Stilfontein, and Hartbeesfontein), South

Half of the 480 trial participants will be enrolled in the
Americas (Haiti, Jamaica, Brazil and the United States) and half
in southern Africa (Botswana and South Africa). The geographic
diversity of participants allows the researchers to evaluate
whether the immune responses generated to the vaccine vary ac-
cording to the amount of prior exposure to adenovirus, as meas-
ured by pre-existing levels of adenovirus antibodies. Africans,
for example, generally have had greater exposure to adenovirus
than people living in North America.

The participants, divided into two groups, will receive four in-
jections spread out over a period of six months. One group will
receive three injections of the naked DNA component followed by
a booster injection of the adenoviral vector component. The sec-
ond group will receive four injections of a placebo vaccine con-
sisting of sterile saltwater. Because the study is "double
blind," neither the participants nor the researchers will know
whether a volunteer is receiving the study vaccine or the pla-
cebo until the end of the trial.

Information about enrolling in HVTN 204 can be found at HVTN's
Web site, . For more information about the
VRC and its candidate vaccine, visit .
NIAID is a component of the National Institutes of Health, an
agency of the U.S. Department of Health and Human Services.
NIAID supports basic and applied research to prevent, diagnose
and treat infectious diseases such as HIV/AIDS and other sexu-
ally transmitted infections, influenza, tuberculosis, malaria
and illness from potential agents of bioterrorism. NIAID also
supports research on transplantation and immune-related ill-
nesses, including autoimmune disorders, asthma and allergies.

News releases, fact sheets and other NIAID-related materials are
available on the NIAID Web site at

Leela McCullough, Ed.D.
Director of Information Services
30 California Street, Watertown, MA 02472, USA
Tel: +1-617-926-9400
Fax: +1-617-926-1212

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