The first AIDS vaccine trial in Africa, under preparation for years, has
begun in Uganda. The opening of this Phase 1 trial, sponsored by the
National Institute of Allergy and Infectious Diseases (NIAID), "is an
important step in an attempt to develop HIV vaccines for countries hardest
hit by the AIDS pandemic," comments Anthony S. Fauci, M.D., director of
The Ugandan Minister of Health, Crispus Kiyonga, M.B.Ch.B., adds, "This
trial is part of a long-term, joint program that began in 1991 with our U.S.
and French partners to develop a safe and effective HIV vaccine for Africa.
Broad consultations have taken place and consensus has been reached among
the various stakeholders and interested groups."
The HIV vaccine to be tested in the trial, called ALVAC vCP205, is based on
a canarypox virus that cannot cause disease in humans. Canarypox-based HIV
vaccines, made by Pasteur Mérieux Connaught (Rhône-Poulenc Group, France),
have been tested in more than 800 volunteers in the United States and France
with no serious side effects reported.
The trial is being carried out at the Joint Clinical Research Center in
Kampala and the Uganda Virus Research Institute in Entebbe. Both
laboratories have state-of-the-art equipment and are staffed by highly
trained Ugandans who with their U.S. counterparts will be conducting the
relevant investigations. The study is under the direction of Professors Roy
Mugerwa, M.B.Ch.B., M.Med., of Makerere University, and Jerrold Ellner,
M.D., of Case Western Reserve University in Cleveland. They also oversee
one of the NIAID HIV Network for Prevention Trials (HIVNET) sites in Uganda,
which conducted the groundwork studies in preparation for this and future
trials of HIV vaccines.
"Every person enrolled will be fully informed by our medical staff as to
what will be done in the trial and what risks or benefits may result from
their participation," says Dr. Mugerwa. "The ethical standards applied in
this trial are internationally accepted and are the same as those in the
"Although small in size, this trial is important symbolically as a first
critical step in developing an effective vaccine for Africa," says Dr.
The Phase 1 trial, known as HIVNET 007, will enroll 40 healthy, HIV-negative
adults between 18 and 40 years old who are at low risk for becoming infected
with HIV. The volunteers will be randomly assigned to one of three groups:
20 individuals will receive the HIV vaccine; 10 individuals will serve as
controls by receiving a similar experimental canarypox vaccine for rabies;
and 10 additional control individuals will receive a placebo that does not
contain any vaccine.
Each person will get four injections over six months. During the study,
neither the study participants nor the health professionals involved will
know which type of injection each volunteer receives. At every clinic
visit, volunteers will be counseled about how to avoid HIV exposure during
The study will last one year, with one additional year of follow-up to
monitor safety and the durability of the immune responses to the vaccine.
Specifically, they will monitor reactions to the vaccines and look for
immune responses directed against HIV itself (neutralizing antibodies) or
against cells infected with HIV (cytotoxic T lymphocytes, or CTLs). Apart
from this information on the vaccine's safety and potential for protection,
no information on its effectiveness can be obtained from this small trial.
The ALVAC vCP205 vaccine cannot cause HIV infection. First, the vaccine
contains only three HIV genes, which by themselves cannot produce an
infectious virus. Second, these genes are inserted into a weakened version
of the canarypox virus. Canarypox virus serves solely as the gene carrier,
or vector, to safely express specific HIV proteins known to elicit immune
responses against HIV. Because canarypox virus can not replicate in human
cells, no new canarypox viruses are formed.
SEARCHING FOR CROSS-REACTIVE IMMUNE RESPONSES
The genes in the vaccine come from only clade B viruses, the predominant
subtype of HIV found in the United States and Europe. However, the
researchers will look for immune responses to clades A and D, as well as
clade B viruses, because the former two subtypes cause most HIV infections
Recent experiments have revealed that CTLs taken from people naturally
infected with clade A or D viruses can recognize clade B viruses in the
laboratory. This is known as cross-reactivity.
"Although laboratory data suggest that some vaccines such as this canarypox
vaccine stimulate broadly reactive CTLs, this needs to be evaluated in human
clinical trials," says Margaret Johnston, Ph.D., assistant director for
HIV/AIDS vaccines at NIAID and associate director of the vaccine and
prevention research program in NIAID's Division of AIDS.
"If the answer is yes, and the levels of cross-reactivity in most volunteers
are significant, then Uganda and its partners can consider moving this
vaccine into larger trials," adds Dr. Johnston. "If not, we will need to
more strongly encourage development of vaccines based on viruses circulating
in different countries."
THE URGENT NEED FOR HIV VACCINE RESEARCH IN AFRICA
Notably, this study represents the first systematic test of any HIV vaccine
in an African population. One of the urgent needs in HIV vaccine research,
says Dr. Johnston, is to understand how human differences influence the
immune response to candidate vaccines. The outcome of this study, she says,
will guide NIAID's future HIV vaccine strategy and is an important step in a
long process toward developing safe and effective HIV vaccines for worldwide
Today, Uganda's population numbers 20 million. According to Dr. Kiyonga,
the rates of HIV infection range from 4 to 10 percent in rural areas to
between 10 and 25 percent in urban locales. Nearly half a million Ugandans
have already died of AIDS. As is true in all of Africa, the disease is
primarily passed from person-to-person through heterosexual sex. A
devastating consequence has been the 1 million orphaned Ugandan children.
In addition to NIAID and the government of Uganda, organizations involved in
facilitating the trial include Makerere University; the Joint Clinic
Research Center; the Uganda Virus Research Institute; UNAIDS; Case Western
Reserve University; the Fogarty International Center of the National
Institutes of Health; and Pasteur Mérieux Connaught.
NIAID is a component of the National Institutes of Health (NIH). NIAID
conducts and supports research to prevent, diagnose and treat illnesses such
as HIV disease and other sexually transmitted diseases, tuberculosis,
malaria, asthma and allergies. NIH is an agency of the U.S. Department of
Health and Human Services.
Press releases, fact sheets and other NIAID-related materials are available
on the NIAID Web site at http://www.niaid.nih.gov.