Volunteers are being recruited through NIAID's AIDS Vaccine
Evaluation Group (AVEG), which includes six clinical units located in
St. Louis, Nashville, Seattle, Birmingham, Baltimore and Rochester (NY).
These new trials bring the total number of vaccine protocols in human
volunteers conducted through the AVEG to 45, using 22 different vaccine concepts.
More than 2,400 volunteers have participated in AVEG preventive HIV
vaccine studies since 1988.
According to Jack Killen, M.D., director of NIAID's Division of AIDS,
"These three trials are part of NIAID's comprehensive approach to HIV
vaccine development. Each of these studies will test a new idea or
approach toward an effective, safe HIV vaccine."
In AVEG 027, an experimental HIV vaccine already being studied as
an injected product will also be applied topically to specific mucosal
sites, for example, the moist tissues lining the nose and mouth, vagina and rectum.
Later, antibodies will be measured at those sites. Most HIV infections,
such as those acquired through sexual exposure, are transmitted across
mucosal surfaces. A vaccine that induces mucosal antibodies may work better
than other types of vaccines against this most common form of exposure.
In AVEG 028, a new strategy -- based on a weakened form of
Salmonella bacteria -- will be used to present an HIV protein to the
immune system. Because this bacteria normally reproduces only inside human
cells, it can present the HIV proteins in a way that may induce better immune
responses than other vaccines.
In AVEG 033, a novel adjuvant, GM-CSF, is being combined with a
canarypox virus-based vector containing HIV genes. GM-CSF is a drug
commonly used to improve blood cell production in cancer patients. This
study will determine if GM-CSF can improve the immune response to the
Additional information about each trial follows.
AVEG 027 is evaluating sequential doses of live recombinant
canarypox ALVAC-HIV vCP205 delivered first by injection and then
as a topical solution applied to the mucosa.
ALVAC-HIV vCP205 is made from a weakened canarypox virus used
as a vaccine for birds. The canarypox virus can fit large pieces of
foreign DNA in its genome, infect human cells and cause them to produce foreign
proteins. ALVAC-HIV vCP205 contains copies of genes for three pieces of
HIV -- the surface protein, the core protein and one enzyme. When the
ALVAC vaccine infects human cells, the cells make proteins from the
genes and package the proteins into HIV-like particles called pseudovirions.
Although not infectious, these pseudovirions fool the immune system and
trigger an immune response. ALVAC-HIV vCP205 has already been tested
in AVEG studies involving more than 700 volunteers.
Eighty-four volunteers will receive the vaccine or a placebo control at
entry, one, three and six months. Volunteers will first receive an
intramuscular injection to prime the immune response. Booster doses
will be administered either intramuscularly or via a swab, nose drops or other
method to mucosal surfaces of the nose, mouth, vagina or rectum. This
is the first study in humans to examine vaginal and nasal administration of
an HIV vaccine.
ALVAC vCP205 is being supplied by Pasteur Merieux Connaught
(Lyon, France). The study is being conducted at all six AVEG sites:
the University of Alabama at Birmingham, the University of Rochester Medical
Center, the University of Washington, Johns Hopkins University,
Vanderbilt University and the University of St. Louis. Peter Wright, M.D., of
Vanderbilt University, chairs the study.
AVEG 028 applies a new vector vaccine approach to HIV vaccine
research. Vector vaccines use a non-disease-causing virus or bacteria
to transport HIV or other foreign genes into the body. In this case, a
gene for the HIV envelope protein, gp120, is inserted into a weakened form of
Salmonella bacteria to make the vaccine, called VVG203. The weakened
Salmonella vector should retain only a transient, unsustainable ability
to replicate in human cells. To assess the safety of VVG203 and to
determine whether it is sufficiently attenuated, volunteers will be closely
followed for symptoms of typhoid fever.
Live-vector approaches offer many advantages over other vaccines
including the ability to induce long-lasting antibody and cell-mediated
immune responses, and the relatively low cost of production. In
addition, because the vaccine is administered orally, it may stimulate the
production of mucosal antibodies.
AVEG 028 will assess if the VVG203 vaccine is safe and how the
body's immune system responds to the vaccine when it is given alone or
sequentially with another AIDS vaccine, HIV-1 MN rgp120. The study will
also determine the optimal dose and immunization schedule. The 12-month
trial, to be conducted at the Johns Hopkins University AVEG site, will
enroll 47 adults at low risk of HIV infection. Mary Lou Clements-Mann, M.D.,
M.P.H., of Johns Hopkins University, is the study chair.
VVG203 was developed at the University of Maryland Center for
Vaccine Development in Baltimore by a research team led by David Hone,
Ph.D., who currently is affiliated with the Institute of Human Virology,
also in Baltimore. This is the first vaccine without industry sponsorship that
NIAID has brought from the laboratory to clinical trials. VaxGen, based in
South San Francisco, Calif., manufactures the MN rgp120 subunit vaccine used
in the study.
AVEG 033 uses a new adjuvant with ALVAC to attempt to induce
better immune responses. An adjuvant enhances or modifies the immune-
stimulating properties of a vaccine. The only licensed adjuvants for
use in human vaccines are alum compounds. Alum may act in part by stimulating
certain chemical messengers, called cytokines.
In this study, volunteers are being given a recombinant cytokine,
human granulocyte-macrophage colony stimulating factor (GM-CSF), as the
adjuvant. GM-CSF may elicit a stronger immune response than alum when
given directly with a vaccine.
GM-CSF is presently used to boost blood cell counts in transplant and
cancer patients. It also can increase the ability of important immune
system cells known as antigen presenters to initiate and direct immune responses.
When used as an adjuvant, GM-CSF may enhance both antibody and cellular
responses to the vaccine. The vaccine being used in AVEG 033 is
ALVAC-HIV vCP205, which primarily stimulates the cellular immune response. The
study investigators will evaluate the ability of GM-CSF to enhance both
cellular and antibody responses to vCP205. The 36 volunteers enrolled
in the study will be followed for 18 months.
The study is being conducted at four AVEG sites: the University of
Alabama at Birmingham, the University of Rochester Medical Center, Johns
Hopkins University and Vanderbilt University. Thomas Evans, M.D., of
the University of Rochester Medical Center, chairs the study. GM-CSF is
being supplied by Immunex (Seattle), and ALVAC-HIV vCP205 is being supplied by
Pasteur Merieux Connaught.
More information about these trials can be obtained by calling the
AIDS Clinical Trials Information Service (1-800-TRIALS-A) or by
visiting their Web site at http://www.actis.org.
NIAID, part of the National Institutes of Health (NIH), supports
biomedical research to prevent, diagnose and treat illnesses such as
AIDS, 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 via the NIAID home page at http://www.niaid.nih.gov.