NIAID Launches Phase II Trial of a New HIV/AIDS Vaccine
A
novel experimental HIV vaccine
targeted to multiple HIV subtypes found worldwide has moved into
the second phase of clinical testing, the National Institute of
Allergy and Infectious Diseases (NIAID), announced today. The
study investigators plan to enroll a total of 480 participants
at sites in Africa, North America, South America and the Caribbean
to test the safety and immune response to the vaccine.
The experimental vaccine was developed by scientists at NIAID’s
Dale and Betty Bumpers Vaccine Research Center (VRC) and is being
studied in the HIV Vaccine Trials Network (HVTN), a clinical research
collaboration funded by NIAID’s Division
of AIDS (DAIDS).
This
trial marks an important step in the advancement toward an effective
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 subtype 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 common 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 reconstitute
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 respiratory 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., principal 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, including African
Americans and other ethnic minorities.
The study is being led by Michael Keefer, M.D., of the University
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; Birmingham,
AL; Nashville, TN; and Rochester, NY
South America: Rio de Janeiro and San Paulo, Brazil
Caribbean: Port-au-Prince, Haiti; Kingston, Jamaica
Africa: Gaborone, Botswana; and Cape Town,
Soweto, and KOSH (Klerksdorp,
Orkney, Stilfontein, and Hartbeesfontein),
South Africa
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 according to the amount of prior exposure to adenovirus,
as measured 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 injections
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 second group
will receive four injections of a placebo vaccine consisting 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 placebo until the end of
the trial. Information about enrolling in HVTN 204 can be found
at HVTN’ Web site, www.hvtn.org.
For more information about the VRC and its candidate vaccine,
visit www.vrc.nih.gov.
10/17/05
Source
NIAID
News
