Challenges in Designing HIV Vaccines
Vaccines teach the immune system to recognize a specific harmful organism
and fight off the disease when the body faces the real thing. Despite
extraordinary advances in understanding both HIV and the human immune
system, a fully successful HIV vaccine continues to elude researchers.
The most difficult challenges today for HIV vaccine researchers are:
- HIV attacks CD4+ T cells, the most important part of the immune system
that coordinates and directs the activities of other types of immune
cells that combat intruding microbes. For a vaccine to be effective,
it will need to be able to activate these cells-a difficult feat if
they're being infected and destroyed by the virus.
- Scientists have not identified the correlates of immunity, or protection,
for HIV and are still trying to design vaccines to induce the appropriate
immune responses necessary for protection. Unlike other viral diseases
for which investigators have made successful vaccines, there are no
documented cases of complete recovery from HIV infection. Therefore,
HIV vaccine researchers have no human model of recovery from infection
and subsequent protection from re-infection to guide them.
- In an infected person, HIV continually mutates and recombines to evolve
into new strains of virus that differ slightly from the original infecting
virus. This extensive diversity of HIV poses a challenge to vaccine
design as an HIV vaccine would need to protect against many different
strains of the virus circulating throughout the world. Conventional
vaccines have had to protect against one or a limited number of strains.
- Ideally, an HIV vaccine will marshal two kinds of immune responses
to fight HIV: T cells and antibodies secreted by B cells. These immune
responses would prevent the establishment and spread of the virus from
the original site of infection and decrease the effects of the disease
in those who do become infected. However, scientists have not yet been
able to stimulate both types of responses. To date, researchers have
only stimulated T cell responses weakly with experimental HIV vaccines,
and have had difficulty stimulating the production of antibodies that
protect against a broad range of HIV strains.
- Researchers lack the knowledge about which HIV immunogens, pieces
of HIV used to construct an experimental HIV vaccine, will get the immune
system to recognize HIV during an actual encounter and protect against
- Lack of a practical animal model to predict the effectiveness of an
HIV vaccine in people hampers HIV vaccine development. Currently, researchers
rely on experiments using non-human primate models infected with the
simian cousin of HIV, known as SIV, and an engineered combination of
SIV and HIV, known as SHIV, to somewhat mimic disease progression. Evaluating
experimental vaccines in these animals requires a SIV or SHIV analog
instead of the actual HIV vaccine candidate used in clinical trials
NIAID is a component of the National Institutes of Health. NIAID
supports basic and applied research to prevent, diagnose and treat infectious
diseases such as HIV/AIDS and other sexually transmitted infections,
influenza, tuberculosis, malaria and illness from potential agents of
bioterrorism. NIAID also supports research on transplantation and immune-related
illnesses, including autoimmune disorders, asthma and allergies.
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Last Updated May 17, 2007 (alt)