Adjuvant
A substance sometimes included in a vaccine formulation to enhance or modify its immune-stimulating properties.

Adverse Reaction
(Also called side effect) In a clinical trial, an unwanted effect detected in participants and attributed to the study vaccine.

AIDS
(Acquired Immunodeficiency Syndrome) The late stage of HIV disease, characterized by a deterioration of the immune system and a susceptibility to a range of opportunistic infections and cancers.

Antibody
(Also called immunoglobulin) An infection-fighting protein in blood or secretory fluids that recognizes, neutralizes, and helps destroy pathogenic microorganisms (e.g., bacteria, viruses) or toxins. Antibodies are made and secreted by B-lymphocytes in response to stimulation by antigens. Generally, each antibody binds only to the specific antigen that stimulated its production.

Antigen
Any substance that is recognized by a component of the immune system (i.e. antibodies, cells). Antigens are often agents such as invading bacteria or viruses. (See immunogen.)

Arm
In a trial, a group of participants in a clinical trial who receive the same treatment, intervention, or placebo. Other arms receive different treatments.

Attenuated
Weakened. Attenuated viruses are often used as vaccines because they can no longer produce disease but may still stimulate a strong immune response. Examples include vaccines against polio (Sabin oral vaccine), measles, mumps, and rubella.

B-Lymphocyte
(B-cell) White blood cells of the immune system, derived from bone marrow and spleen. B-cells develop into plasma cells, which produce antibodies.

Binding Antibody
An antibody that attaches to some part of a pathogen, such as HIV. Binding antibodies may or may not lead to elimination of the pathogen.

Blinded Study
A clinical trial in which participants are unaware whether they are in the experimental or control arm. (See double-blind study.)

Booster
A second or subsequent vaccine dose given after the primary dose, to increase immune responses. A booster vaccine may or may not be the same as the primary one. (See prime-boost.)

Breakthrough Infection
An infection which the vaccine is intended to prevent, but that nevertheless occurs in a volunteer during a vaccine trial.

Canarypox
A virus that infects birds and is being used to carry HIV genes into human cells in several HIV vaccines now in clinical trials. Canarypox virus cannot grow in human cells, an important safety feature. (See vector.)

CD
Abbreviation for "cluster of differentiation," referring to molecules on the surface of immune cells. CD markers are used to identify stages of maturation of immune cells, for example, CD4+ T-cells.

CD4+ T-Lymphocyte
(Also called helper T-cell) Immune cell that carries a CD4 marker on its surface. CD4+ cells are the primary targets of HIV. They help orchestrate both antibody and killer T-cell responses. (See T-cell.)

CD8+ T-Lymphocyte
Immune cell that carries the "cluster of differentiation 8" (CD8) marker. CD8 T-cells may be cytotoxic (killer) T-cells or suppressor T-cells. (See CTL; T-cell.)

Cell-Mediated Immunity
(Also called cellular immunity) The branch of the immune system that targets host cells infected with microorganisms such as viruses, fungi, and certain bacteria. It is coordinated by helper T-cells and CTLs.

Challenge
In vaccine experiments, the deliberate exposure of an immunized animal to the infectious agent. Challenge experiments are never done in human HIV vaccine research.

Clade
(Also called sub-type) A group of related HIV isolates classified by their degree of genetic similarity. There are two major groups of HIV-1 isolates, called M and O. Group M consists of at least eight clades, A through H. (See isolate.)

Cohort
Groups of individuals who share one or more characteristics in a research study and who are followed over time. For example, a vaccine trial might include two cohorts, a group at low risk for HIV and a group at higher risk.

Control
An inactive substance (also known as a placebo) sometimes given to trial participants. In a vaccine trial, the control group is compared with one or more groups of volunteers given experimental vaccines.

Core
The protein capsule surrounding a virus DNA or RNA. In HIV, the precursor for the core protein (called p55) is broken down into the smaller molecules p24, p17, p7, and p6. HIVs core is primarily composed of p24.

Correlates of Immunity
(Also called correlates of protection) The specific immune responses that correlate with protection from a certain infection. The precise correlates of immunity for HIV are unknown.

Cytokine
A group of soluble, hormone-like proteins produced by white blood cells and that act as messengers between cells. Cytokines can stimulate or inhibit the activity of immune cells and may prove useful as immunologic adjuvants.

Deletion
Elimination of a gene, in nature or in the laboratory.

Dendritic Cell
An immune cell with thread-like tentacles called dendrites that "capture" antigen and present it to T-cells. Examples of dendritic cell types include Langerhans cells, found in the skin, and follicular dendritic cells, found in lymphoid tissues.

DNA
(Deoxyribonucleic acid) The genetic material of all living things (except for RNA-carrying viruses, such as HIV). DNA is a double-stranded, helical molecular chain found within each cell. It contains the information needed for cells to produce proteins, molecules that enable cells to reproduce and carry out their functions.

DNA Vaccine
An experimental vaccine technology in which one or more genes coding for specific antigen(s) are directly injected into the body, where they hopefully produce antigen(s) in the recipient and trigger immune responses. The technology is highly promising for producing simple, inexpensive and heat-stable vaccines.

Double-Blind Study
A clinical trial in which neither the study staff nor the participants know which participants are receiving the experimental vaccine and which are receiving placebo. Double-blind studies are thought to produce the most objective results.

DSMB
(Data and Safety Monitoring Board) A committee of independent clinical research experts who review data while a clinical efficacy trial is in progress to ensure that participants are not exposed to undue risk. Also monitors the trial for differences in infection rates between those receiving the vaccine and those receiving placebos.

Efficacy
In vaccine research, the ability of a vaccine to protect vaccinated people against a specific infection or disease. A vaccine may be tested for efficacy in Phase III trials if (smaller) Phase I and Phase II trials show it to be safe and promising.

ELISA
(Enzyme-linked immunosorbent assay) A blood test that detects antibodies and is often used to test whether a person is infected with HIV.

Endpoint
The final results of an intervention, such as vaccination, compared among different groups in a clinical trial. In early vaccine trials, common endpoints are safety and specific types and levels of immune responses (e.g., neutralizing antibodies, CTLs).

Enhancing Antibody
A type of antibody that may increase the ability of a pathogen to infect cells and produce disease. It is currently unknown whether enhancing antibodies have any effect on the course of HIV infection. Enhancing antibodies can be thought of as the opposite of neutralizing antibodies.

Env
A gene of HIV that codes for gp160, the precursor molecule that gets split into the envelope proteins gp120 and gp41. (See glycoprotein.)

Envelope
Outer surface of a virus, also called the coat. Not all viruses have an envelope. (See virus; env.)

Enzyme
Proteins that accelerate the rate of a specific chemical reaction without themselves being altered. Enzymes are generally named by adding the suffix "-ase" to the name of the substance on which the enzyme acts (for example, protease is an enzyme that acts on proteins).

Epitope
A specific site on an immunogen that stimulates specific immune responses, such as the production of antibodies or activation of immune cells.

Expression System
In genetic engineering, the cells into which a gene has been inserted, with the aim of producing its encoded protein. Chinese hamster ovary (CHO) cells and baculovirus/insect cells are two expression systems often used to make recombinant HIV vaccines.

Gag
An HIV gene that codes for p55. p55 is the precursor of HIV proteins p17, p24, p7 and p6 that form HIVs core, the inner protein shell surrounding the viral RNA.

Genetic Engineering
The laboratory technique of splicing together genes to produce specific proteins, for example, to use as medications (such as insulin) or vaccines.

Genome
The complete DNA present in an individual cell or virus.

Gp
(Glycoprotein) A protein molecule with one or more branches of sugar molecules attached to it. Many cellular and viral proteins are glycoproteins, including the outer coat proteins of HIV. A number after the gp (e.g., gp160, gp120, gp41) is the molecular weight of the glycoprotein.

Gp120
(Glycoprotein 120) The glycoprotein on the outer surface of the HIV envelope. gp120 binds to the CD4+ molecule on helper T-cells during infection. It has been studied as an experimental HIV vaccine because the outer envelope is the first part of the virus "seen" by neutralizing antibodies.

Gp41
(Glycoprotein 41) A protein embedded in the outer envelope of HIV that anchors gp120. gp41 plays a key role in HIVs entry into CD4+ T-cells by facilitating the fusion of the viral and cell membranes.

Helper T-Cell
T-lymphocyte bearing the CD4+ cell surface marker. Helper T-cells are the chief regulatory cells of the immune system, controlling activities such as turning antibody production on and off. They are the main targets of HIV infection. (See CD4+ T-lymphocyte.)

HIV
(Human Immunodeficiency Virus) The etiologic agent that causes AIDS.

HLA
(Human leukocyte antigen) A diverse group of human cell surfaces molecules that play important roles in cellular immunity.

Immune Complex
The result of binding between an antigen and its specific antibody. Such antigen-bound antibody may or may not cause adverse reactions in people.

Immune Deficiency
A breakdown or inability of certain parts of the immune system to function, thus making people susceptible to diseases that they would not ordinarily develop.

Immune Response
The bodys reaction to foreign antigens. This response may neutralize or eliminate the antigens and provide immunity.

Immunity
Natural or vaccine-induced resistance to a specific disease. Immunity may be partial or complete, specific or nonspecific, long-lasting or temporary.

Immunization
The process of inducing immunity by administering a vaccine, thereby "teaching" the immune system to recognize certain antigen(s) and thus prevent infection or illness when it subsequently encounters the infectious agent.

Immunogen
A substance capable of provoking an immune response.

Immunoglobulin
A general term for antibodies, which recognize invading organisms, leading to their destruction. There are five classes of immunoglobulins: IgA, IgG, IgM, IgD and IgE.

In Vitro
A laboratory environment outside living organisms (e.g., a test tube or culture plate) used to study diseases and biological processes.

In Vivo
Testing within a living organism, e.g., human or animal studies.

Inclusion/exclusion Criteria
The medical or social reasons detailing the grounds by which a person qualifies for participation in a clinical trial. For example, some trials may exclude people with chronic liver disease or certain drug allergies.

Informed Consent
An agreement signed by all volunteers participating in a clinical research study, indicating their understanding of: (1) why the research is being done; (2) what researchers hope to learn; (3) what will be done during the trial, and for how long; (4) what risks are involved; (5) what, if any, benefits can be expected from the trial; (6) what other interventions are available; and (7) the participants right to leave the trial at any time. (See protocol.)

Investigational New Drug
Investigational New Drug (IND). An investigational drug is one that is under study but does not yet have permission from the U.S. Food and Drug Administration (FDA) to be legally marketed and sold in the United States. FDA approval is the final step in the process of drug development. The first step in the process is for the new drug to be tested in the laboratory. If the results are promising, the drug company or sponsor must apply for FDA approval to test the drug in people. This is called an Investigational New Drug (IND) Application. Once the IND is approved, clinical trials can begin.

IRB
(Institutional Review Board) A committee of physicians, statisticians, community representatives and others that review clinical trial protocols before they can be initiated at a specific institution. IRBs ensure that a trial is ethical and that the rights of participants are adequately protected.

Isolate
A particular strain of HIV-1 from a person (primary isolate) or cultured cell line (laboratory isolate).

Lymphocyte
The diverse set of white blood cells (each with different functions) that are responsible for immune responses. There are two main types: B-cells (responsible for producing antibodies) and T-cells (which orchestrate all aspects of the immune response and carry out specialized functions such as destroying cells infected with pathogens). The cells are produced in the bone marrow and thymus, respectively.

Macrophage
A type of large immune cell that devours invading pathogens and other intruders. Macrophages stimulate other immune cells by "presenting" them with small pieces of the invaders. Macrophages also can harbor large quantities of HIV without being killed, and may therefore act as viral reservoirs.

Memory Cell
Memory cells are long-lived subsets of T-cells and B-cells that have been exposed to specific antigens and can "recall" them (and then quickly mobilize an immune response) even if infection occurs many years later.

MHC
(Major Histocompatibility Complex, also called HLA in humans) The gene cluster that controls certain aspects of the immune response.

MN
An HIV-1 strain belonging to clade B, the most prevalent clade in North America and Europe. MN has been widely used in vaccine development.

Monoclonal Antibodies
A collection of identical antibodies that recognizes the same single epitope.

Mucosal Immunity
Resistance to infection across the bodys mucous membranes. Mucosal immunity depends on immune cells and antibodies present in the linings of the reproductive and gastrointestinal tracts and other moist body surfaces exposed to the outside world (the most frequent routes of HIV infection).

Nef
A gene present in SIV and HIV that is not required for but regulates viral reproduction. Vaccines made of live SIV-lacking nef (nef-deleted) have been studied in monkeys.

Neutralizing Antibody
An antibody that prevents virus from infecting a cell, usually by blocking viral entry points (receptors) on the virus.

P24
A protein in HIV's inner core. The p24 antigen blood test is often used to detect HIV infection.

Parenteral
Administered intravenously or by injection. Vaccines may be administered by injection into the fatty layer immediately below the skin (subcutaneous), or into the muscle (intramuscular). Medications, but not vaccines, can also be administered into a vein (intravenous).

PCR
(Polymerase Chain Reaction) A sensitive laboratory method used to detect and measure amounts of RNA or DNA. Used to determine viral load in people infected with HIV.

Peptide
A molecule made of two or more linked amino acids. Proteins are made of peptides.

Phase I
A Phase I vaccine trial is a clinical trial with a small number (usually 60 or less) of healthy volunteers, typically at low-risk for HIV infection. Phase I trials test a vaccine's safety in humans, including its metabolic and pharmacologic actions and any side effects seen with increasing doses.

Phase II
A Phase II vaccine trial is a controlled clinical study to identify common short-term side effects and risks associated with the test vaccine and to collect expanded information on its immunogenicity. Phase II trials enroll some volunteers with characteristics similar to potential participants of an efficacy (Phase III) trial. They enroll up to several hundred participants and generally have two or more arms.

Phase III
A Phase III vaccine trial is a large controlled study to determine the ability of a vaccine to produce a desired clinical effect on the risk of a given infection, disease, or other clinical condition at an optimally selected dose and schedule. These trials also gather additional information about safety needed to evaluate the overall benefit-risk relationship of the vaccine. Phase III trials usually include several hundred to several thousand volunteers.

Placebo
An inactive substance given to some study participants, while others receive the test substance (e.g., a vaccine). Placebos provide a basis for comparison. (See control.)

Prevalence
The proportion of people with a particular disease or condition in a specific population and at a given time.

Priming
(Also called prime-boost) Giving one vaccine dose to induce certain immune responses, to be followed by or together with a second type of vaccine (booster). A prime-boost combination may induce different types of immune responses and/or enhance overall responses beyond those seen with only one type of vaccine.

Protocol
The detailed plan for a clinical trial, outlining its rationale, purpose, methodologies (such as vaccine dosages, routes of administration, length of study, eligibility criteria) and other aspects of trial design.

Pseudovirion
A particle resembling a virus but lacking its genetic information, and therefore unable to replicate. In some viral diseases, pseudovirions interfere with infection by the real infectious virus.

Randomized Trial
A study in which participants are assigned by chance to one of two or more arms of the trial. Randomization minimizes the differences among groups by equally distributing people with particular characteristics among all the trial arms.

Receptor
A molecule on the cell surface that serves as a recognition or binding site for a specific antigen, antibody, enzyme or other molecule.

Regulatory Genes
HIV genes (nef, rev, tat, vpr) whose protein products are not required for but help regulate viral replication in infected cells.

Retrovirus
HIV and other viruses that carry their genetic material in the form of RNA rather than DNA. These viruses also contain the enzyme, reverse transcriptase, which transcribes RNA into DNA. That process is the opposite of what normally occurs in animals and plants, where DNA is made into RNA; hence the prefix "retro."

RNA
(Ribonucleic acid) A single-stranded molecule composed of chemical building blocks similar to those DNA. RNA is the sole genetic material of retroviruses and an intermediary in making proteins in all living things.

Seroconversion
The development of antibodies to a particular antigen. When people develop antibodies to HIV or an experimental HIV vaccine, they "seroconvert" from antibody-negative to antibody-positive. Vaccine-induced seroconversion is not an infection.

SHIV
A genetically engineered "hybrid" virus with an HIV envelope and SIV core. SHIV is widely used for testing vaccines in monkeys.

SIV
(Simian Immunodeficiency Virus) An HIV-like virus that infects monkeys and causes an AIDS-like disease in some species.

Statistical Significance
The probability that an observed difference (for example, between two arms of a vaccine trial) is due to the vaccine rather than to chance alone. This probability is determined by using statistical tests to evaluate collected data.

Sterilizing Immunity
An immune response that completely prevents the establishment of any detectable infection.

Strain
One type of HIV. HIV is very heterogeneous, with no two isolates exactly the same. When HIV is isolated from an individual and studied in the lab, it is given its own unique identifier, or strain name (i.e., MN, LAI).

Sub-Unit Vaccine
A vaccine consisting of only one protein from the virus or other pathogen. HIV sub-unit vaccines produced by genetic engineering are called recombinant sub-unit vaccines.

Subtype
(Also called clade) For HIV, a classification scheme based on genetic differences among isolates.

T-Cell
One of two main types of white blood cells critical to the immune system. They include CD4+ and CD8+ T-cells. The "T" stands for the thymus, where T-lymphocytes mature. (See lymphocyte.)

T-Lymphocyte Proliferation Assay
A test used to measure the memory of T-cells to antigens such as HIV, specifically their ability to replicate which happens only if they have "seen" the antigen before.

V3 Loop
A part of the HIV gp120 surface protein that appears to be important in stimulating neutralizing antibodies.

Vaccinia
A cowpox virus, formerly used in human smallpox vaccines and now as a vector in some experimental HIV vaccines.

Vector
A bacterium or virus that does not cause disease in humans and is used in genetically engineered vaccines to transport antigen-encoding genes into the body to induce an immune response. Examples include vaccinia and canarypox.

Viremia
The presence of virus in the bloodstream.

Virus
A microorganism composed of a piece of genetic material ( RNA or DNA ) surrounded by a protein coat. To replicate, a virus must infect a cell and direct its cellular machinery to produce new viruses.

Western Blot
A blood test to detect antibodies to specific components of a virus such as HIV. This test is most often used to confirm a positive ELISA.