AIDS: Acquired Immunodeficiency Syndrome
AIDSVAX®: The trade name for all formulations of VaxGen’s vaccine. AIDSVAX is made by cloning a protein from the surface of HIV called gp120. Because the protein used in AIDSVAX is synthetic and contains no infectious agent, it is incapable of causing HIV or AIDS. Click here for more information about AIDSVAX.
Adjuvant: The active ingredient in vaccines that improves the human immune system response by attracting immune cells into the region where the vaccine is injected. The adjuvant in AIDSVAX is alum, or aluminum hydroxide.
Antibody: An infection-fighting protein molecule in blood that attaches to and neutralizes viruses. Antibodies are made in response to stimulation by antigens. Each specific antibody binds only to the specific antigen that stimulated its production.
Antibody Immunity: Immunity from a virus that results from the activity of antibodies in the blood.
Antigen: The ingredient in vaccines that activates the human immune system response. The antigen in AIDSVAX is a synthetic gp120 protein.
Bivalent Vaccine: A vaccine designed to protect against two strains of virus. For example: AIDSVAX B/B is a bivalent vaccine designed to prevent infection by the BMN strain, which is believed to represent the majority of HIV in North America. It is also designed to protect against a second strain, BGNE8, or B’. By reformulating AIDSVAX from a monovalent to a bivalent vaccine, the number of different types of antibodies it produces increased to seven from four. We believe these seven antibodies cover virtually all known HIV strains in North America. Eventually, AIDSVAX may become a multivalent vaccine that protects against virtually all strains worldwide. Click here for more information about the design of AIDSVAX.
Booster: Any vaccine injection received after the primary dose(s) and used to boost the immune response. Volunteers in the VaxGen trials receive three primary doses followed by four booster shots, one every six months for 24 months.
Breakthrough Infection: An infection that breaks through a vaccine’s protective barrier. Breakthroughs usually are caused by viral strains for which the vaccine was not designed to protect. Once the breakthrough strains have been identified, they can be cloned and incorporated into the vaccine to broaden its protection.
Chemokine Receptors: The second of two receptors on the surface of human T cells to which HIV’s gp120 binds to enter the cell. Click here for more information.
CD4 Receptors: The first of two receptors on the surface of human T cells to which HIV’s gp120 binds to enter the cell.
CD4+ T Cells: The type of immune cell that is the primary target of HIV. Also known as helper T cells, CD4+ T cells help orchestrate the immune response, including antibody production.
CD8+ T Cells: See cytotoxic T lymphocytes.
Clinical Trials (vaccines): Human trials. All new vaccines must pass three stages of testing in humans before they can be considered for regulatory licensure. Most HIV vaccine candidates have failed to pass the first two phases. AIDSVAX is the only preventive HIV/AIDS vaccine that has progressed to Phase III.
- Phase I — tests for safety and dosage
- Phase II — larger-scale tests for safety and determination of whether the vaccine stimulates antibodies and immune memory
- Phase III — Large-scale, placebo-controlled, double-blind tests to determine how well the vaccine is working. These tests must be performed in thousands of individuals who are HIV-negative but at high risk of contracting the disease.Click here for more information about VaxGen’s clinical trials.
Correlates of Protection: The type of immune response that must be present to protect an individual from infection. Once a correlate of protection is known, a vaccine can be improved to increase its ability to protect against infection.
Cytotoxic T Lymphocyte (CTL): Also known as killer T cells, CTL’s are a type of immune cell that can destroy cells that are already infected by a virus. CTL’s are a proposed, but as yet unproven method for protecting against HIV infection.
Double-Blind Study: A clinical trial in which neither the vaccine manufacturer, clinicians nor the participants know which participants are receiving the vaccine or a placebo. Double-blind studies are considered the most objective method for measuring the effectiveness of a drug. All of VaxGen’s clinical trials are double blind.
Data and Safety Monitoring Board: An independent group of clinical research experts who oversee clinical trials. VaxGen’s DSMB oversees its trials in North America, Europe and Thailand. Headed by the former deputy director of the Centers for Disease Control and Prevention, VaxGen’s DSMB also includes prominent clinicians, AIDS specialists, an ethicist, vaccinologists and biostatisticians from the United States and Thailand. The DSMB reviews VaxGen’s trials every six months to ensure safety. No serious adverse events associated with the vaccine were observed in the four reviews that have been conducted so far. In November of 2001, the DSMB is scheduled for the first time to examine trial data to determine how well the vaccine is working.
gp120: Glycoprotein 120 is a protein found on the surface of HIV, and it is the key to the HIV infection process. In a two-step process, gp120 binds to a pair of receptors on the surface of human cells, allowing the entire virus to enter the cell and replicate. A synthetic version of gp120 is the primary ingredient in AIDSVAX.
gp160: Gp120 is attached to another protein beneath the surface of the HIV particle called gp41. Together, the two proteins are known as gp160.
Host: A plant or animal in which a disease originates and is harbored. Chimpanzees are the host animal for HIV.
Humoral Immunity: See antibody immunity
Immunity: The natural or acquired ability of the immune system to resist a specific disease.
Immunization: The process of administering a vaccine that trains the body’s immune system to neutralize a given infectious agent.
Immunodeficiency: The breakdown of the immune system to the point where it can no longer prevent diseases that normally would not develop.
Immunogen: See antigen.
Immunogenicity: The ability of an antigen or vaccine to stimulate an immune response. AIDSVAX is considered highly immunogenic because it produces an immune response in everyone who receives it. VaxGen’s Phase III trials are designed to determine how well that immune response prevents HIV infection.
Immunosuppression: When the body’s immune system is compromised and can’t perform its normal function. Can be a result of HIV infection.
Interim Analysis: Analyses conducted before the scheduled endpoint of a Phase III clinical trial to determine how well a drug is working. An interim analysis of VaxGen’s North American/European trial is scheduled for November 2001. If the vaccine is shown to be effective, the DSMB will recommend that VaxGen halt the trial and vaccinate the placebo recipients. The company would also begin the process of applying for regulatory approval to manufacture and market AIDSVAX. If the interim analysis is inconclusive, the trial will continue to its scheduled endpoint 12 months later, gathering additional statistical power along the way with which to determine the vaccine’s efficacy.
Leukocytes: All classes of white blood cells, including T cells.
Lymphocytes: A type of white blood cell that is primarily responsible for the immune response. Present in the blood, lymph and lymphoid tissue.
Macrophage: A type of immune system cell that stimulates other immune cells by presenting them with particles of invading bacteria and virus. It can also devour invaders and is known to harbor large quantities of HIV without being killed.
Neutralizing Antibody: The kind of antibody that prevents a virus from entering a cell. It is hoped that AIDSVAX will produce neutralizing antibody, because if HIV is prevented from entering cells it cannot replicate and dies within the bloodstream with a few hours.
Placebo: An inactive substance given to some trial participants while others receive an active ingredient. Comparing the infection rates between those who received placebo and vaccine determines how well the vaccine prevents infection.
Reactogenicity: The capacity of a vaccine to produce adverse reactions. The reactogenicity of AIDSVAX has been minimal so far.
Retrovirus: The class of viruses to which HIV belongs. Retroviruses carry their genetic material in the form of RNA instead of DNA. Once they have entered a human cell, they use an enzyme called reverse transcriptase to direct the cell to produce DNA from their viral RNA. This process allows the virus to multiply.
SHIV: A genetically engineered virus with an HIV surface and an SIV core. Often used in laboratory testing.
SIV: Simian Immunodeficiency Virus. An HIV-like virus that causes an AIDS-like disease in some species of monkeys.
Strains: A subset of a subtype. For example: The HIV subtype B has two strains, T tropic and M tropic. Both of these strains, in turn, produce two additional strains.
Subtypes: The largest classification of HIV isolates. There are five major subtypes of HIV —A, B, C, D, E — each of which contains a group of related HIV isolates. Also known as clades.
T Cell: A type of white blood cell that is a critical component of the immune system.
Vaccine: A preparation that trains the body’s immune system to protect itself from an invading virus.
Virus: A microorganism comprised of either DNA or RNA with a protein coat. Viruses invade healthy cells and then use the host cell to replicate, spreading disease or infection. HIV, the virus that causes AIDS, is particularly dangerous because it attacks the body’s immune system cells.
Sources: VaxGen; AIDS Vaccine Advocacy Coalition’s HIV Vaccine Handbook; thebody.com