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A
ADCC (antibody-dependent cellular cytotoxicity): an
immune response in which an infected target cell that is coated with
antibody is destroyed by an immune cell.
adjuvant: a substance sometimes included in a vaccine
formulation to enhance or modify the immune-stimulating properties of
a vaccine.
adverse events: toxicities or side effects that may arise during a clinical trial. There are grading scales for adverse events that investigators use to classify adverse events from mild to more serious. The term is used whether or not the effect can be attributed to the vaccine under study.
adverse reaction (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.
ALVAC-HIV: a genetically engineered HIV vaccine
composed of a live, weakened canarypox virus (ALVAC) into which
parts of genes for non-infectious components of HIV have been inserted.
When ALVAC infects a human cell, the inserted HIV genes
direct the cell to make HIV proteins. These proteins are packaged into
HIV-like particles that bud from the cell membrane. These particles
are not infectious but fool the immune system into mounting an immune
response to HIV. ALVAC can infect but not grow in human cells,
an important safety feature. (See also canarypox.)
amino acid: any of the 26 chemical building blocks
of proteins.
anamnestic response: the heightened immunologic reaction
elicited by a second or subsequent exposure to a particular pathogenic
microorganism (e.g., bacterium, fungus, virus), toxin, or antigen. (See
also memory cells.)
anergy: the loss or weakening of immune response to
an irritating agent or antigen. Anergy can be thought of as the opposite
of allergy, which is an overreaction to a substance. The strength of
the immune response is often quantitatively evaluated by standardized
skin tests. A small amount of solution containing an antigen known to
cause a response, such as tetanus, mumps, or candida, is injected under
the skin and the area checked for a localized skin reaction after 48
to 72 hours. Healthy people will develop a measurable area of redness
at the injection site; people who are immune suppressed, such as people
with AIDS, will have no measurable response to these skin tests.
antibody: an infection-fighting protein molecule in
blood or secretory fluids that tags, neutralizes, and helps destroy
pathogenic microorganisms (e.g., bacteria, viruses) or toxins. Antibodies,
known generally as immunoglobulins, are made and secreted by B lymphocytes
in response to stimulation by antigens. Each specific antibody binds
only to the specific antigen that stimulated its production. (See also
immunoglobulin ; binding antibody
; enhancing antibody ; functional antibody
; neutralizing antibody.)
antibody-mediated immunity: also called humoral immunity.
Immunity that results from the activity of antibodies in blood and lymphoid
tissue.
antigen: any substance that stimulates the immune
system to produce antibodies. Antigens are often foreign substances
such as invading bacteria or viruses. (See also immunogen.)
antigen-presenting cell (APC): B cell, macrophage,
dendritic cell or other cell that ingests and processes foreign bodies
such as viruses and displays the resulting antigen fragments on its
surface to attract and activate the CD4+ T cells that respond specifically
to that antigen. (See also dendritic cell ; macrophage.)
anti-idiotype: an antibody that recognizes and binds
to the antigen-binding site of another antibody. In HIV vaccines, anti-idiotype
vaccines are made from antibodies generated against antibodies to the
virus.
apoptosis: cellular suicide, also known as programmed
cell death. A possible mechanism used by HIV to suppress the immune
system. HIV may cause apoptosis in both HIV-infected and HIV-uninfected
immune system cells.
arm: a group of participants in a clinical trial,
all of whom receive the same treatment, intervention or placebo. The
other arm(s) receive(s) a different treatment.
attenuated: weakened. Attenuated viruses are often
used as vaccines because they can no longer produce disease but still
stimulate a strong immune response, like that to the natural virus.
Examples of attenuated virus vaccines include oral polio, measles, mumps,
and rubella vaccines.
autoimmunity: in HIV vaccination, a theoretical
adverse effect in which the vaccine causes immune responses that are
inappropriately directed at a person's own tissues.
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B
B lymphocyte (B cell): one of the two major classes
of lymphocytes, B lymphocytes are white blood cells of the immune system
that are derived from the bone marrow and spleen. B cells develop into
plasma cells, which produce antibodies.
baculovirus: an insect virus used in the production
of subunit vaccines. By splicing a specific HIV gene(s) into the baculovirus
genome, and then combining this construct with insect cells, mass quantities
of the purified HIV protein(s) coded for by these two HIV gene(s) can
be made by the cells for use as a vaccine. (See also expression
system.)
baseline: the time point in a study just before initiation
of intervention (vaccination) when starting measurements are taken.
Measurements taken at later time points may be compared with those taken
at baseline to study variations.
binding antibody: an antibody that attaches to some
part of HIV. Binding antibodies may or may not lead to the killing of
the virus.
blinded study: a clinical trial in which participants
are unaware as to whether or not they are in the experimental or control
arm of the study. (See also double-blind study.)
booster: a second or later vaccine dose given after
the primary dose(s) to increase the immune response to the original
vaccine antigen(s). The vaccine given as the booster dose may or may
not be the same as the primary vaccine. (See also prime-boost.)
bDNA (branched DNA) assay: laboratory test for measuring
the amount of virus in blood plasma. The test detects an amplified luminescent
signal whose brightness depends on the amount of viral RNA present.
breakthrough infection: an infection, which the vaccine
is intended to prevent, that occurs in a volunteer during the course
of a vaccine trial. Such an infection is caused by exposure to the infectious
agent and may occur before or after the vaccine has taken effect or
all doses have been given.
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C
canarypox: a virus that infects birds and
is used as a live vector for HIV vaccines. It can carry a large quantity
of foreign genes. Canarypox virus cannot grow in human cells, an important
safety feature. (See also ALVAC- HIV vector.)
CD: abbreviation for 'cluster of differentiation'
referring to cell surface molecules that are used to identify stages
of maturity of immune cells, for example, CD4+ T cells.
CD4+ T lymphocyte:
immune cell that carries a marker on its surface known as 'cluster
of differentiation 4' (CD4). These cells are the primary targets
of HIV. Also known as helper T cells, CD4+ T cells help orchestrate
the immune response, including antibody responses as well as killer
T cell responses. (See also T cell.)
CD8+ T lymphocyte:
immune cell that carries the 'cluster of differentiation 8'
(CD8) marker. CD8 T cells may be cytotoxic T lymphocytes or suppressor
T cells. (See also cytotoxic T lymphocyte (CTL);
T cell.)
cell-mediated immunity (cellular immunity): the immune
response coordinated by helper T cells and CTLs. This branch of the
immune system targets cells infected with microorganisms such as viruses,
fungi and certain bacteria.
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.
CHO (Chinese hamster ovary) cell: a cell used as a
'factory' in genetic engineering to make certain subunit vaccines.
CHO cells are derived from mammals and are advantageous because they
add carbohydrates (a sugar coat) to the protein, much like naturally
infected human cells do.
clade: also called a subtype.
A group of related HIV isolates classified according to their degree
of genetic similarity (such as of their envelope proteins). There are
currently two groups of HIV-1 isolates, M and O. M consists of at least
nine clades, A through I. Group O may consist of a similar number of
clades. (See also isolate.)
clinical trial: a research study commonly designed to measure if a new or experimental drug or vaccine is safe and effective for use in humans (safety and efficacy). Clinical trials are conducted in a controlled setting and involve volunteer participants.
Scientists first study the drug or vaccine in the test tube (preclinical) and laboratory animals (animal studies) to be sure that it is safe enough to begin testing in humans. The original dosing of a drug in humans is based on the results of the animal studies.
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 for HIV.
complement: blood proteins that play an important
role in the immune response. Generally, complement proteins amplify
the effects of antibodies and inflammation.
control: in a clinical trial, the control group is the group of participants which does not receive the active intervention, ie the experimental vaccine, microbicide or drug. In HIV prevention trias, control group participants do receive the same package of proven prevention services as the group that is receiving the experimental substance. In some studies, control group participants may receive a licensed vaccine, like hepatitis B, or an inactive substance which is indistinguishable from the experimental agent. In all other respects, the control and intervention arm receive identical care. This allows researchers to compare the control group with one or more groups of volunteers given experimental interventions to detect any additional beneficial effects.
core: the protein capsule surrounding a virus;
DNA or RNA. In HIV, p55, the precursor molecule to the core, is broken
down into the smaller molecules p24, p17, p7 and p6. HIV's core
is primarily composed of p24.
correlates of immunity (correlates of protection):
the immune responses that must be present to protect an individual from
a certain infection. The precise correlates of immunity in HIV transmission
are unknown.
cytokine: a soluble, hormone-like protein produced
by white blood cells that acts as a messenger between cells. Cytokines
can stimulate or inhibit the growth and activity of various immune cells.
Cytokines are essential for a coordinated immune response and can also
be used as immunologic adjuvants. HIV replication is regulated by a
delicate balance among cytokines.
cytoplasm: the living matter within a cell (excluding
the nucleus) that is responsible for the function of the cell (for example,
protein synthesis).
cytotoxic T lymphocyte (CTL): immune
system cell that can destroy cancer cells and cells infected with viruses,
fungi or certain bacteria. CTLs, also known as killer T cells, carry
the CD8 marker. CTLs kill virus-infected cells, whereas antibodies generally
target free-floating viruses in the blood. CTL responses are a proposed
but unproven correlate of HIV immunity. (See also CD8+ T lymphocyte.)
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D
data and safety monitoring board (DSMB): a committee of independent clinical research experts who review data while a clinical trial is in progress. The DSMB ensures that participants are not exposed to undue risk and looks for any differences in effectiveness between the experimental and control groups. The DSMB may review the data in such a way that they know which group received the vaccine and which group did not. This group may also recommend that a trial be modified or stopped if there are safety concerns or if the trial objectives have been achieved. The DSMB provides periodic review of interim data to and recommendations to study investigators and the trial IRB (see IRB).
deletion: elimination of a gene either in nature or
in the laboratory.
dendritic cell: immune cell with threadlike tentacles
called dendrites used to enmesh antigen, which they present to T cells.
Langerhans cells, found in the skin, and follicular dendritic cells,
found in lymphoid tissues, are both types of dendritic cells. (See also
antigen-presenting cell.)
DNA (deoxyribonucleic acid): the double-stranded,
helical molecular chain found within the nucleus of each cell. DNA carries
the genetic information that encodes proteins and enables cells to reproduce
and perform their functions.
DNA vaccine (nucleic acid vaccine): direct injection
of a gene(s) coding for a specific antigenic protein(s), resulting in
direct production of such antigen(s) within the vaccine recipient in
order to trigger an appropriate immune response.
domain: a region of a gene or gene product. A neutralizing
domain is a specific site on the virus to which a neutralizing antibody
is directed.
dose-ranging study: a clinical trial in which two
or more doses (starting at a lower dose and proceeding to higher doses)
of a vaccine are tested against each other to determine which dose works
best and has acceptable side effects.
dose-response relationship: the relationship between
the dose of a vaccine and an immune or physiologic response. In vaccine
research, a dose-response effect means that as the dose of the vaccine
increases, so does the level of the immune response (antibodies and
CTL activity).
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 a placebo or another therapy. Double-blind trials are thought to produce objective results, since the researchers' and volunteers' expectations about the experimental vaccine do not affect the outcome.
DSMB: see Data and Safety Monitoring Board
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E
EBV (Epstein-Barr Virus) cell line: a herpesvirus;
in vaccine research, used to make target cells for CTL assays.
efficacy: in HIV prevention research, the ability of an experimental intervention to produce a desired effect, such as protection against HIV infection or reduction in viral load set point, in the context of a clinical trial. “Efficacy trials” gather information on whether or not a product provides some benefit. Efficacy is different from effectiveness, which is the term used to describe the benefits of the strategy when it is introduced in “real world” settings, versus the carefully controlled environment of a clinical trials.
ELISA (enzyme-linked immunoabsorbent assay): a blood
test that detects antibodies based on a reaction that leads to a detectable
color change in the test tube. The HIV ELISA is commonly used as the
initial screening test because it is relatively easy and inexpensive
to perform. Because the HIV ELISA is designed for optimal sensitivity; that is, it detects all persons with HIV antibodies as well as
some who don't have them (false positives); a positive HIV
ELISA test must be confirmed by a second, more specific test such as
an HIV Western Blot.
empirical: based on experience or observational information
and not necessarily on proven scientific data. In the past, vaccine
trials have been performed based exclusively on empirical data and without
a full understanding of the disease processes or correlates of immunity.
emulsion: a suspension of droplets of one liquid in
another liquid (such as oil and water). The two liquids do not actually
combine but are instead suspended within one another.
endpoint: the results of an intervention such as vaccination
compared among different study groups in a clinical trial. In early
vaccine trials, common endpoints are safety and specific types and intensities
of immune responses (neutralizing antibodies, CTL responses).
enhancing antibody: a type of binding antibody, detected
in the test tube and formed in response to HIV infection, that may enhance
the ability of HIV to produce disease. Theoretically, enhancing antibodies
could attach to HIV virions and enable macrophages to engulf the viruses.
However, instead of being destroyed, the engulfed virus may remain alive
within the macrophage, which then can carry the virus to other parts
of the body. 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.
enrollment: recruitment of volunteer participants in a clinical trial.
env: a gene of HIV that codes for gp160,
the precursor molecule that breaks down into the envelope proteins gp120
and gp41. (See also gp.)
envelope: outer surface of a virus, also called the
coat. Not all viruses have an envelope. (See also virus; env.)
enzyme: a protein produced by cells to accelerate
a specific chemical reaction without itself being altered. Enzymes are
generally named by adding the ending -ase to the name of
the substance on which the enzyme acts (for example, protease is an
enzyme that acts on proteins).
epidemiology: the study of the frequency and distribution
of disease in human populations.
epitope: a specific site on an antigen that stimulates
specific immune responses, such as the production of antibodies or activation
of immune cells.
expanded access programs: these are programs that provide consumers with access to experimental drugs that have shown promise in clinical trials, but have not yet received full FDA approval to be marketed.
expression system: in genetic engineering, the cells
into which a gene has been inserted to manufacture desired proteins.
Chinese hamster ovary (CHO) cells and baculovirus/insect cells are two
expression systems that are used to make recombinant HIV vaccines.
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F
food and drug administration (FDA): The top drug regulatory body that is responsible for approving medicines in the United States. All drugs require FDA approval before they can be marketed. FDA approval is based on the agency’s review of clinical trial data. Dietary supplements do not require FDA approval.
functional antibody: an antibody that binds to an
antigen and has an effect that can be demonstrated in laboratory tests.
For example, neutralizing antibodies are functional antibodies that
inactivate HIV or prevent it from infecting other cells.
futility: a clinical trial is deemed futile when a review of interim data suggests that it is extremely unlikely that the trial, if it continues to its normal end, will have the statistical proof needed to convince a regulatory agency to approve the experimental treatment.
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G
gag: a gene of HIV that codes for
p55, the core protein. p55 is the precursor of HIV proteins p17, p24,
p7 and p6 that form HIV's capsid or core, the inner protein shell
surrounding HIV's strands of RNA.
genetic engineering: the laboratory technique of recombining
genes to produce proteins used for drugs and vaccines.
genome: the complete set of genes present in a cell
or virus.
gp: abbreviation for glycoprotein. A protein molecule
that is glycosylated, that is, coated with a carbohydrate, or sugar.
The outer coat proteins of HIV are glycoproteins. The number after the
gp (e.g., gp160, gp120, gp41) is the molecular weight of the glycoprotein.
gp41: glycoprotein 41. A protein imbedded in the outer
envelope of HIV that anchors gp120. gp41 plays a key role in HIV's infection
of CD4+ T cells by facilitating the fusion of the viral and
cell membranes. Antibodies to gp41 can be detected on a screening HIV
ELISA.
gp120: glycoprotein 120. One of
the proteins that forms the envelope of HIV. gp120 projects from the
surface of HIV and binds to the CD4 molecule on helper T cells. gp120
has been a logical experimental HIV vaccine because the outer envelope
is the first part of the virus that encounters antibody.
gp160: glycoprotein 160, a precursor
of HIV envelope proteins gp41 and gp 120.
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H
half-life: the time required for half the amount of
a substance to be eliminated from the body or to be converted to another
substance(s).
helper T cell: lymphocyte bearing the CD4
marker. Helper T cells are the chief regulatory cells of the immune
response. They are responsible for many immune system functions, including
turning antibody production on and off, and are the main target of HIV
infection. (See also CD4+ T lymphocyte.)
homologous: similar in appearance, structure and usually
function. For HIV, the same strain of the virus.
host: a plant or animal harboring another organism.
HLA (human leukocyte antigen): two major classes of
molecules on cell surfaces.
HLA class I: molecules that exist on all nucleated
cells and identify the cell as "self." In addition, if the
cell is infected by a virus or other microbe, the cell displays the
invader's antigens in combination with the cell's HLA class
I molecules. The presence of the foreign peptide antigen with the HLA
class I molecule activates CD8+ CTLs specific for that antigen.
HLA class II: molecules that are found on antigen-presenting
cells such as macrophages. These cells process soluble antigens such
as toxins or other proteins made by microbes and then display them on
their surface as peptide antigens in combination with HLA Class II molecules.
Helper T cells specific for these antigens are then able to be activated
and respond to the presence of the invading microbe.
humoral immunity: see antibody-mediated immunity.
hypothesis: a tentative statement or supposition,
which may then be tested through research.
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I
immune complex: the result of a reaction between an
antigen and a specific antibody. This combination of antigen bound by
antibody may or may not cause adverse effects in a person.
immune deficiency: a breakdown or inability of certain
parts of the immune system to function, thus making a person susceptible
to diseases that they would not ordinarily develop.
immunity: natural or acquired resistance provided
by the immune system 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 an antigen (vaccine) to allow the immune system to prevent
infection or illness when it subsequently encounters the infectious
agent.
immunogen: a substance capable of provoking an immune
response. Also called an antigen.
immunocompetent: capable of developing an immune response;
possessing a normal immune system.
immunogenicity: the ability of an
antigen or vaccine to stimulate immune responses.
immunoglobulin: a general term for antibodies, which
bind to invading organisms, leading to their destruction. There are
five classes of immunoglobulins: IgA, IgG, IgM, IgD and IgE. (See also antibody.)
immunotherapy: a treatment that stimulates or modifies
the body's immune response.
incidence: the rate of occurrence of some event, such
as the number of individuals who get a disease divided by a total given
population per unit of time. (Contrast with prevalence.)
inclusion/exclusion criteria: the medical or social
reasons why a person may or may not qualify for participation in a clinical
trial. For example, some trials may exclude people with chronic liver
disease or with certain drug allergies; others may include only people
with a low CD4+ T-cell count.
IND (investigational new drug): the status of an experimental
drug after the FDA agrees that it can be tested in people.
informed consent: the process by which prospective volunteers for a clinical research trial receive information about the risks and benefits of the study and agree to participate in the trial. One part of the informed consent process is the signing of a document that that indicates the participants’ willingness to be in the trial and their understanding of (1) why the research is being done, (2) what researchers want to accomplish, (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 participant's right to leave the trial at any time. True informed consent is an ongoing process, which revisits participants’ beliefs about, expectations and understanding of the trial, as well as the voluntariness of their participation, throughout the duration of the study.
institutional review board (IRB): a committee of physicians, statisticians, community advocates and others that reviews clinical trial protocols before they can be initiated. IRBs ensure that the trial is ethical and that the rights of participants are adequately protected. IRBs are housed at the institutions or in the countries which are conducting the research. They are therefore part of the local oversight system for ethical research.
intervention: a vaccine (or drug or behavioral therapy)
used in a clinical trial to improve health or alter the course of disease.
in vitro: an artificial environment created outside
a living organism (e.g., in a test tube or culture plate) used in experimental
research to study a disease or biologic process.
in vivo: testing within a living organism, e.g., human
or animal studies.
IRB: see institutional review board
isolate: a particular strain of HIV-1 taken from a
person.
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L
LAI: an HIV-1 isolate used in HIV vaccine development.
LAI is also referred to as IIIB or LAV. LAI belongs to clade B, the
clade to which most HIV-1 found in America and Europe belongs. (See
also clade.)
live, replicating vector: also referred to as a replication competent vector, this refers to a safe, non-disease-causing bacterium or virus which has retained its ability to copy itself, or replicate. This type of vector is used to carry synthetic genetic material into human cells. Replication competent vectors for AIDS vaccines are being explored as a possible strategy for inducing strong HIV-specific immune responses.
live viral vector: a live viral vector is a safe, non-disease-causing bacterium or virus which is used to carry synthetic genetic material from HIV (or other pathogens) into human cells. The vector is one strategy for introducing the genetic material (see antigen) in a way that is elicits a strong immune response. The live viral vector is not capable of ongoing replication. (See also live, replicating vector)
lymphocyte: a type of white blood cell produced in
the lymphoid organs that is primarily responsible for immune responses.
Present in the blood, lymph and lymphoid tissues. (See also B
cell and T cell.)
lymphoid tissue: tonsils, adenoids, lymph nodes, spleen
and other tissues that act as the body's filtering system, trapping
invading microorganisms and presenting them to squadrons of immune cells
that congregate there.
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M
macrophage: a large immune system cell in the tissues
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,
acting as reservoirs of the virus.
mean: the arithmetic average, or the sum of all the
values divided by the number of values.
median: the midpoint value obtained by ranking all
values from highest to lowest and choosing the value in the middle.
The median divides a population into two equal halves.
memory cell: memory cells are a subset of T cells
and B cells that have been exposed to specific antigens and can then
proliferate (recognize the antigen and divide) more readily when the
immune system re-encounters the same antigens. (See also anamestic
response.)
MHC (major histocompatibility complex): the gene cluster
that controls certain aspects of the immune response. Among the products
of these genes are the histocompatibility antigens, such as HLA class
I antigens, which are present on every cell with a nucleus and serve
as markers to distinguish self from non-self. (See also HLA.)
microencapsulated: surrounded by a thin layer of biodegradable
substance referred to as a microsphere. A means of protecting a drug
or vaccine antigen from rapid breakdown. Microencapsulation may also
enhance an antigen's absorption and the immune response to that
antigen.
MN: an HIV-1 strain belonging to clade B, the clade
to which most HIV-1 found in North America and Europe belong. MN is
used in vaccine development. (See also clade.)
monoclonal antibody: custom-made, identical antibody
that recognizes only one epitope.
monocyte: a large white blood cell in the blood that
ingests microbes or other cells and foreign particles. When a monocyte
passes out of the bloodstream and enters tissues, it develops into a
macrophage.
monovalent vaccine: a vaccine that contains only one
antigen.
mucosal immunity: resistance to infection across the
mucous membranes. Mucosal immunity depends on immune cells and antibodies
present in the linings of reproductive tract, gastrointestinal tract
and other moist surfaces of the body exposed to the outside world.
multisite trials: trials that take place at multiple sites and may involve different test populations.
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N
nef: a gene of SIV and HIV that regulates
the production of the virus. Vaccines made of SIV virions from which
nef has been removed (nef-deleted) have shown promise
in monkeys.
neutralizing antibody: an antibody
that keeps a virus from infecting a cell, usually by blocking receptors
on the cells or the virus.
neutralizing domain: a section of HIV (most commonly
on the envelope protein gp120) that elicits antibodies with neutralizing
activity. (See also V3 loop.)
NK cell (natural killer cell): a non-specific lymphocyte.
NK cells, like killer T cells, attack and kill cancer cells and cells
infected by microorganisms. NK cells are 'natural' killers
because they do not need to recognize a specific antigen in order to
attack and kill.
nucleus: the central controlling body within a living
cell, usually a spherical unit enclosed in a membrane and containing
genetic codes for maintaining life systems of the organism and for issuing
commands for growth and reproduction.
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O
open-label trial: a clinical trial in which doctors
and participants know which vaccine is being administered to all participants.
opportunistic infection: an illness caused by an organism
that usually does not cause disease in a person with a normal immune
system. People with advanced HIV infection suffer opportunistic infections
of the lungs, brain, eyes and other organs.
overwhelming benefit: a term used to define the undeniably superiority of a given intervention in a clinical trial.
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P
p24: a protein in HIV's inner core. The p24 antigen
test looks for the presence of this protein in a person's blood.
parenteral: administered intravenously or by injection.
For example, medications or 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 (intravenously).
pathogenesis: the origin and development of a disease.
More specifically, it's the way a microbe (bacteria, virus, etc.)
causes disease in its host.
PBMC (peripheral blood mononuclear cell): cells in
the bloodstream that have one round nucleus; e.g., lymphocytes and monocytes.
Usually, the majority of circulating PBMCs are lymphocytes.
PCR (polymerase chain reaction): a sensitive laboratory
technique used to detect and repeatedly copy small amounts of RNA or
DNA. Some PCR tests can also quantify the amount of RNA or DNA. PCR
is used to measure viral load in persons infected with HIV.
peptide: a short compound formed by linking two or
more amino acids. Proteins are made of multiple peptides.
PHA (phytohemagglutinin): a plant chemical used to
stimulate the multiplication (proliferation) of T lymphocytes in laboratory
tests.
phase 1 vaccine trial: a closely
monitored clinical trial of a vaccine conducted in a small number of
healthy volunteers. A Phase 1 is designed to determine the vaccine's
safety in humans, its metabolism and pharmacologic actions, and side
effects associated with increasing doses.
phase 2 vaccine trial: controlled
clinical study of a vaccine to identify common short-term side effects
and risks associated with the vaccine and to collect information on
its immunogenicity. Phase 2 trials enroll some volunteers who have the
same characteristics as persons who would be enrolled in an efficacy
(Phase 3) trial of a vaccine. Phase 2 trials enroll up to several hundred
participants and have more than one arm.
phase 3 vaccine trial: 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
and to provide adequate basis for labeling. Phase 3 trials usually include
several hundred to several thousand volunteers.
pharmacokinetics: the processes of absorption, distribution,
metabolism and excretion of a drug or vaccine.
placebo: an inactive substance administered to some study participants while others receive the agent under evaluation, to provide a basis for comparison of effects.
placebo effect: this term refers to results that be linked with any medication or treatment, even a sugar pill or inert or ineffective treatment (placebo), simply because the recipient believes that the treatment will work.
plasmid: an extrachromosomal ring of DNA, especially
of bacterial origin, that replicates autonomously.
pol: a gene of HIV that codes for
the enzymes protease, reverse transcriptase and integrase.
polymerase: an enzyme that creates genetic material,
either RNA or DNA, from building blocks.
polyvalent vaccine: a vaccine that is produced from
multiple viral strains, or is made to induce immune responses against
multiple strains.
prevalence: the number of people in a given population
affected with a particular disease or condition at a given time. Prevalence
can be thought of as a snapshot of all existing cases at a specified
time. (Contrast with incidence.)
preventive HIV vaccine: a vaccine
designed to prevent HIV infection.
priming: giving one vaccine dose(s) first
to induce certain immune responses, followed by or together with a second
type of vaccine. The intent of priming is to induce certain immune responses
that will be enhanced by the booster dose(s).
prime-boost: in HIV vaccine research,
administration of one type of vaccine, such as a live-vector vaccine,
followed by or together with a second type of vaccine, such as a recombinant
subunit vaccine. The intent of this combination regimen is to induce
different types of immune responses and enhance the overall immune response,
a result that may not occur if only one type of vaccine were to be given
for all doses.
prophylaxis: prevention of disease.
protease inhibitor: one of a class of anti-HIV drugs
designed to inhibit the enzyme protease and interfere with virus replication.
Protease inhibitors prevent the cleavage of HIV precursor proteins into
active proteins, a process that normally occurs when HIV replicates.
protocol: a document that details the goals, design, methodology, statistical considerations and organization of a clinical trial. The protocol will have a study plan that describes what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study.
pseudovirion: a virus-like particle that resembles
a virus but does not contain its genetic information and cannot replicate.
In some viral diseases pseudovirions can interfere with infection by
the real infectious virus.
purchase capacity: people in resource-limited countries often must
wait a decade or longer to have access to vaccines and treatments after they
are licensed for use in wealthier countries. In order to ensure rapid
global access to an AIDS vaccine, rich countries, international
organizations, and other funders will need to work together to create
significant resources to purchase and deliver vaccines.
The Global Fund to Fight AIDS, Malaria, and TB is one example
of an international effort to expand purchase capacity for necessary
health products. In the past, legislative proposals
have sought to create purchase funds for AIDS and other vaccines.
Others have proposed that rich countries and international
organizations "pre-commit" to buying AIDS vaccines for global use when these
products become available.
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R
randomized trial: a study in which participants are assigned by chance to one of two or more intervention arms or regimens. Randomization is a selection process in which test subjects are randomly assigned to a control or experimental group to assure the different treatment groups are 'statistically equivalent'. (Also used: randomized-controlled trial (RCT)). Randomization minimizes the differences among groups by equally distributing people with particular characteristics among all the trial arms.
reactogenicity: the capacity of a vaccine to produce
adverse reactions.
reagent: any chemical used in a laboratory test or
experiment.
receptor: a molecule on the surface of a cell that
serves as a recognition or binding site for antigens, antibodies or
other cellular or immunologic components.
recombinant DNA technology: the technique by which
genetic material from one organism is inserted into a foreign cell in
order to mass produce the protein encoded by the inserted genes.
regulatory agencies: these play a critical role in
health care research by reviewing proposals for research in human
subjects and considering vaccine and other products for licensure.
These agencies have a tough job, as they must ensure the safety of
research subjects involved in testing novel health products while not
unnecessarily delaying approval of valuable health research or
product approval. In the United States, the Food and Drug Administration
(FDA) is the lead regulatory agency involved in health care research.
The European Medicines Evaluation Agency (EMEA) is the lead
regulatory agency for the European Union. Many other countries have
their own regulatory agencies as well. Currently, the World Health Organization
is reviewing regulatory capacity in countries around the
world and helping to expand this capacity.
regulatory gene: HIV genes (nef, rev, tat, vpr)
that regulate viral replication in infected cells.
retrovirus: HIV and other viruses that carry their
genetic material in the form of RNA rather than DNA and have the enzyme
reverse transcriptase that can transcribe it into DNA. In most animals
and plants, DNA is usually made into RNA, hence 'retro' is
used to indicate the opposite direction.
reverse transcriptase: the enzyme produced by HIV
and other retroviruses that enables them to direct a cell to synthesize
DNA from their viral RNA.
RNA (ribonucleic acid): a single-stranded molecule
composed of chemical building blocks, similar to DNA. The RNA segments
in cells represent copies of portions of the DNA sequences in the nucleus.
RNA is the sole genetic material of retroviruses.
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S
safety: one of the two main measurements of a clinical trial, in addition to efficacy. Laboratory and animal studies of the safety of an experimental drug are done prior to testing in humans.
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 does not represent
an infection. Instead, vaccine-induced seroconversion is an expected
response to vaccination that may disappear over time.
serostatus: positive or negative results of a diagnostic
test, such as an ELISA, for a specific antibody.
SF-2: an HIV-1 strain used in vaccine development.
SF-2 belongs to clade B, the clade to which most HIV-1 strains found
in North America and Europe belong. (See also clade.)
SHIV: genetically engineered hybrid virus having an
HIV envelope and an SIV core.
side effect: (See adverse reaction.)
SIV (simian immunodeficiency virus): an HIV-like virus
that infects and causes an AIDS-like disease in some species of monkeys.
statistical significance: the probability that an
event or difference occurred as the result of the intervention (vaccine)
rather than by chance alone. This probability is determined by using
statistical tests to evaluate collected data. Guidelines for defining
significance are chosen before data collection begins.
sterilizing immunity: an immune response that completely
prevents the establishment of an infection.
stoppage: discontinuation of a clinical trial.
strain: one type of HIV. HIV is so heterogeneous,
no two isolates are exactly the same. When HIV is isolated from an individual,
and worked on in the lab, it is given its own unique identifier, or
strain name (i.e., MN, LAI).
stratification: separation of a study cohort into
subgroups or strata according to specific characteristics.
subtype: also called a clade. With
respect to HIV isolates, a classification scheme based on genetic differences.
subunit vaccine: a vaccine that contains only part
of the virus or other microorganism. HIV subunit vaccines produced by
genetic engineering are referred to as recombinant subunit HIV vaccines.
surrogate marker: an indirect measure of disease progression.
In HIV disease, the number of CD4+ T cells per cubic millimeter
of blood is often used as a surrogate marker.
syncytia: giant cells formed by the fusion of an HIV-infected
blood cell with one or more uninfected ones.
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T
T cell: white blood cell critical to the immune response.
Among these are CD4+ T cells and CD8+ T cells.
The 'T' stands for the thymus, where T lymphocytes mature.
(See also lymphocyte.)
T lymphocyte proliferation assay: a test used to measure
the memory of T cells to antigens or microbes, such as HIV.
test-of-concept trial: trials that are smaller than traditional Phase III efficacy trials. They can provide preliminary evidence of efficacy and can help vaccine developers make more informed decisions about whether or not to move the product into a full Phase III trial. The size of test-of-concept trials depends on various factors including the rates of new HIV infections (incidence) in the community where the trial is taking place.
therapeutic HIV vaccine: a vaccine designed to boost
the immune response to HIV in a person already infected with the virus.
Also referred to as an immunotherapeutic vaccine.
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V
V3 loop: a section of the HIV gp120 surface protein
that appears to be important in stimulating neutralizing antibodies.
(See also neutralizing domain.)
vaccine: a preparation that stimulates an
immune response that can prevent an infection or create resistance to
an infection.
vaccinia: a cowpox virus, formerly used in human smallpox
vaccines. Employed as a vector in HIV vaccines to transport HIV genes
into the body.
vector: in vaccine research, a bacterium or virus
that does not cause disease in humans and is used in genetically engineered
vaccines to transport genes coding for antigens into the body to induce
an immune response. (See also vaccinia and canarypox.)
viremia: the presence of virus in the bloodstream.
virion: a mature infectious virus particle existing
outside a cell.
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.
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W
Western blot: a blood test to detect antibodies to
several specific components of a virus such as HIV. This test is most
often used to confirm a positive ELISA.
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