Novel Concepts Put to the Test in Three New AIDS Vaccine Trials

National Institute of Allergy and, Infectious DiseasesFOR RELEASE, Wednesday, January 14, 1998, Laurie K. Doepel, ldoepel@nih.gov

Investigators supported by the National Institute of Allergy and Infectious Diseases (NIAID) have begun enrolling volunteers in three new clinical trials of novel HIV vaccine approaches. The trials are testing a novel route of immunization, an innovative vaccine strategy and a new adjuvant, or vaccine booster.

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 AVEG to 45, using 24 different vaccine concepts. More than 2,400 volunteers have participated in AVEG 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 be applied to specific mucosal sites, for example, the moist tissues lining the respiratory, urinary and reproductive tracts. 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 the common Salmonella bacteria -- will be used to present HIV proteins to the immune system. Because this bacteria normally reproduces only inside human cells, it can present the HIV proteins in a way that may better induce immune responses.

In AVEG 033, a novel adjuvant, GM-CSF, is being combined with a canarypox virus-based vector containing HIV proteins. 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 vector.

Additional information about each trial follows.

AVEG 027

AVEG 027 is evaluating sequential doses of live recombinant canarypox ALVAC-HIV vCP205 delivered first by injection and then via 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 -- more than any other experimental preventive HIV vaccine tested so far. 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 more than 700 volunteers in other AVEG studies.

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 before being given booster doses either intramuscularly or via a swab, nose drops or other method through a variety of mucosal routes: oral, vaginal, nasal and rectal. This is the first study in humans to examine vaginal, nasal and rectal administration of an HIV vaccine.

ALVAC vCP205 is being supplied by Pasteur Merieux Connaught. 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

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, one protein from HIV (gp120) is inserted into the Salmonella bacteria to make the vaccine, called VVG203. VVG203 was genetically engineered at the University of Maryland Center for Vaccine Development in Baltimore to make it incapable of growing or multiplying in humans.

Live-vector approaches offer many advantages 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. Previous studies conducted by the AVEG have used vaccinia and canarypox viruses as vectors. Unlike vaccinia, however, the Salmonella in this vaccine has been modified so it does not reproduce in human cells, which is an important safety feature.

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 trial will enroll 47 adults at low risk of HIV infection.

All six AVEG sites are participating in this study. Mary Lou Clements-Mann, M.D., M.P.H., of Johns Hopkins University, is the study chair. Both vaccines used in this study are manufactured by VaxGen of South San Francisco, Calif.

AVEG 033

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 (Lyon, France).

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.