How Vaccines Work

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How Vaccines Work
Vaccines are designed to stimulate the immune
system to protect against microogranisms such as
viruses.  When a foreign substance invades the
body, the immune system activates certain cells
to destroy the invader. This activation of the
immune system involves two main types of cells B
cells and T cells. B cells make antibodies,
molecules that attach to and neutralize viruses
floating free in the bloodstream, thereby
preventing the viruses from infecting other
cells. T cells can be helper cells or killer
cells. Helper T cells organize the immune
response. Killer T cells (???????)attack cells
infected by viruses.
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Antigen
Microorganisms such as viruses contain many
molecules that are seen as foreign to the body.
These different molecular shapes are called
antigens, or epitopes. The B cells and T cells
are activated by recognizing these antigens. Each
individual T cell or B cell will only recognize
and respond to its individual destiny antigen.
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Cloning
Once a T cell or B cell is activated by its
destiny antigen, the B or T cell clones itself,
making many duplicate copies of itself. Some of
these cloned T cells attack and destroy cells
infected by the invading virus. Other cloned B or
T cells remain in the body as memory cells.
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Immunity
If the body is re-invaded by the virus in the
future, the memory cells will be reactivated and
respond faster and more powerfully to destroy the
virus. This is the principle behind vaccines,
such as the vaccinations we received in childhood
against measles or mumps.
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How AIDS VaccinesAre Developed
To design a vaccine to prevent AIDS, researchers
must start with an idea or strategy.
All products selected for use as a potential AIDS
vaccine go through a rigorous screening process.
This process begins with an idea for attacking
the virus based on vaccine theory and current
knowledge of the disease and its mechanism of
progression. Each candidate vaccine must undergo
extensive pre-clinical evaluation in the
laboratory, small animal models, and in non-human
primates before it is tested in humans
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How AIDS VaccinesAre Developed
The decision to move forward with human trials is
based on pre-clinical results, availability of
the product, and the anticipated promise of the
approach based on related scientific findings. 
In addition, before a vaccine can be administered
to human subjects  it must first undergo review
by the FDA and Institutional Review Boards at
each clinical site.
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Challenges in DevelopingAIDS Vaccines - 1

• HIV continually mutates and recombines. This may
  mean that a vaccine would need to protect the
  person against many strains of the virus.
  Vaccines against other viruses have only had to
  protect the person against one or a limited
  number of strains

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Challenges in DevelopingAIDS Vaccines - 2

• HIV infects helper T cells, the immune cells that
  orchestrate the immune response. It is very
  difficult to design a vaccine that, to be
  effective, needs to activate the very cells that
  are infected by the virus

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Challenges in DevelopingAIDS Vaccines - 3

• HIV can be transmitted as both free virus and in
  infected cells. This may mean that both arms of
  the immune system may need to be stimulated

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Challenges in DevelopingAIDS Vaccines - 4

• Researchers do not know what constitutes an
  effective immune response to HIV. It might be
  antibodies, activated immune cells, perhaps a
  third immune response, or a combination of immune
  responses

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Challenges in DevelopingAIDS Vaccines - 5

• Researchers lack an ideal animal model for AIDS
  vaccine testing.

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New Finding on Immune Response May Contribute to
Vaccine, Treatment
September 22, 2000
Researchers have learned important details of how
the immune system first controls HIV, and how the
virus evades it, through a study in monkeys
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Why Tat (or possibly Gag) vaccine?
There are several biological reasons for
believing that an immune response directed
against Tat (or possibly Gag) may be particularly
effective in controlling HIV. First, these
proteins are less able to change than other parts
of HIV some parts of tat might not be able to
change without making a virus which could not
sustain an infection, and if so, a preventive or
treatment vaccine could be directed against them.
Also, Tat is produced early in the life cycle of
HIV -- before the virus has had time to suppress
immune responses through other mechanisms. And
the immune escape found in this study may be less
of an issue with a preventive vaccine, since
there is much less viral variation and less
chance to produce new mutations. And in any case,
the new vaccine ideas suggested by this study are
readily testable
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Vaccine Advance
Monkeys Still Infected, but Protected from Illness
October 20, 2000
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Monkeys
On October 20, 2000 researchers reported that a
modern high-tech vaccine protected all monkeys
vaccinated from becoming ill from an HIV-like
virus, while half of the control monkeys given a
sham vaccine instead had died of the infection by
day 140. This careful, well-designed experiment
was important in showing that vaccination can
protect against HIV, and in illustrating which
immune mechanisms seem to be protective. But this
vaccine technology is far from ready for human
use -- for example, the virus it protected
against was exactly the same virus used to make
the vaccine, while humans would have to be
protected from a variety of HIV strains.
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Certain proteins
This vaccine used DNA which coded for certain
proteins from the virus in the body, the DNA
produces those proteins, so that the immune
system can be prepared to respond if it
encounters the real virus later. In this
experiment, the vaccination was given as four
doses (at weeks zero, four, eight, and 40)
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For the first time
This test shows for the first time that an HIV
vaccine can work to prevent illness. While this
vaccine did not prevent HIV infection, it made
the infection much less severe. Besides the
benefit to the individual, such a vaccine could
have important public-health benefits in
controlling the epidemic, as persons with an
undetectable or very low viral load are likely to
be much less infectious than those with viral
loads thousands of times higher
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???
It is not known if such a vaccination strategy
could help those already infected -- but animal
tests might give a preliminary answer quickly. In
any case the data from this study will indirectly
help persons with HIV, by providing confirmation
and additional information about what immune
responses are protective. Any therapy (vaccine or
otherwise) that restores those responses in
HIV-positive patients who have lost them should
get more attention
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To develop
This report should also alert those interested
that we are in the middle of a revolution of
vaccine technology -- with enormous potential for
improving health, especially in developing
countries, if it is applied. The technology now
being developed will permit the creation of
rationally designed vaccines made to order for
specific needs