U.S. Company Raises Hopes for AIDS Vaccine    

 

A preventive vaccine against HIV / AIDS could be available by 2005 if results
from human safety and efficacy trials are as good as expected.

Early results from Phase III trials of a preventive AIDS vaccine will not be available
until early next year but its California-based developer VaxGen Inc said
it was optimistic it would work.

 

BEST HOPE TO CONTROL EPIDEMIC

With 40 million people living with HIV/AIDS and infection rates rising, a preventive vaccine is considered the best hope to control
the rampant epidemic.

Drugs have prolonged the lives of sufferers in the West but few in the developing world have access to them.

It is doubtful that the first preventive vaccine will be 100 percent effective against the virus, but experts believe even 30
percent protection could help to curtail the epidemic.

VaxGen's AIDS vaccine works by inducing the immune system to produce antibodies that attach to the gp120 protein on
the surface of the virus. The theory is that by preventing the virus from attaching to the cells it will stop infection.

There are five major subtypes of HIV in different areas of the world. In Thailand there is just one subtype but
Africa has many, so VaxGen is working on vaccines to induce antibodies against several subtypes of HIV.

 

AIDSVAX - Description:

AIDSVAX is the trade name for all formulations of VaxGenís preventive HIV/AIDS vaccine  candidates, two of which
are currently in Phase III clinical trials. AIDSVAX is not a treatment for AIDS or HIV. It is being tested for its ability
to prevent people from becoming infected with HIV.

Like nearly every licensed vaccine, AIDSVAX induces the immune system to produce antibodies. These antibodies are
designed to attach to the protein on the virus surface (gp120) that HIV uses to fuse through and infect healthy cells.
If the antibodies can prevent the virus from attaching to healthy cells, itís believed that they can prevent infection.

Earlier vaccines used live or attenuated virus to trigger an immune response. Because AIDSVAX induces antibodies
using genetically engineered proteins, not the actual virus, it cannot cause HIV infection.

HIV Infection Process
Although a typical exposure to HIV involves thousands of viral particles, only a few, perhaps one to 10,
result in productive infection. If this were the first exposure, the bodyís immune system would be caught off guard
by the foreign invaders. Before it could mount an effective response to neutralize the virus particles, HIV would have
begun to infect human cells and rapidly multiply. Slowly the virus spreads, eventually overwhelming the immune system.

Potential Protection Process
But a different scenario unfolds if the immune system is primed to recognize the virus and is prepared to mount an effective
and rapid response to the initial HIV exposure. In that case, the immune system would neutralize the viral particles before
they had a chance to begin their replication process. Thatís the principle behind AIDSVAX as well as the one that
was used in successful vaccines against polio, smallpox and hepatitis B, among many other diseases.

The primary components of AIDSVAX are genetically engineered proteins. These synthetic proteins are identical
to a protein (gp120) on the surface of HIV, used by the virus to fuse through and infect healthy cells.
The synthetic proteins in AIDSVAX prompt the immune system to produce antibodies to gp120. If the antibodies can
successfully attach to gp120 and prevent the virus from entering cells and replicating, it cannot survive.

Manufacturing Process
Using recombinant DNA technology, the gp120 used in AIDSVAX is cloned from HIV into Chinese hamster ovary cells,
which act as cellular factories to produce commercial quantities of the synthetic version. VaxGen has an exclusive license
from Genentech, developer of the proprietary manufacturing process, to all the technical know-how and genetic material
required to produce synthetic (or recombinant) gp120.

Chimpanzee Studies
Before being tested in humans, two separate tests conducted by Genentech, Inc. demonstrated that vaccine candidates
containing gp120 were able to protect chimpanzees from live HIV infection.
Since chimpanzees are the only laboratory animal susceptible to infection by the virus, the ability to protect them
with a gp120 vaccine was an encouraging step forward.

In the first test, the chimpanzees were vaccinated with a gp120 formulation designed to protect against one particular
strain of HIV. The vaccinated chimps, along with those that received placebo, were then injected with high doses of live
HIV from the same strain used to make the vaccine. All of the vaccinated chimps were protected.

In the second test, the vaccinated chimps were challenged with an HIV strain that was significantly different from the one
used to make the gp120 vaccine. The results were the same: The vaccinated chimps were protected
and the unvaccinated animals became infected.

 

HIV / AIDS: Description Of The Virus

HIV is the virus that causes AIDS. Like other viruses, HIV multiplies by entering and
overtaking the metabolic machinery  of human cells. But HIV is unique because it kills
the very cells that are meant to fight infection ó T cells, a type of white blood cell.
Over the course of several years, HIV systematically destroys these cells, dismantling
the immune system. Eventually, the body is left defenseless against a host of
deadly opportunistic infections and cancers.

 

HIV is spread through blood, semen, breast milk and vaginal fluid, including menstrual fluid. People who contract HIV
may remain healthy for many years and, without testing, may be unaware that they carry the virus. Indeed,
the disease has spread so far and so fast precisely because many people are unaware that they
are infected and so fail to take precautions to prevent spreading it to others.

HIV is also unusual because it is virtually 100% fatal. In the vast majority of cases worldwide, 
HIV leads to death within five to 10 years of infection.

Each HIV particle is composed of an outer layer studded with proteins known as gp120, and a core
that houses its genetic information. In a two-step process, HIV uses gp120 to bind to a pair of receptors
on the surface of T cells, allowing the virus to enter the cell.

Once inside, the HIV virus fuses with the cellís genetic machinery and begins to multiply, producing thousands of progeny.
In time, the T cell bursts like a seedpod, scattering new HIV virus to infect and kill other cells. The cycle is then repeated
countless times.

HIV Variation

Like any virus, HIV has mutated to form distinct subtypes. Today, there are five major subtypes A, B, C, D, and E
each of which tends to predominate in specific areas of the world. All of the HIV subtypes most likely originated
in sub-Saharan Africa. People infected with a single subtype then carried it to specific regions in other parts of the world.
Over time, each subtype became established in different geographical areas. The virus then underwent further mutation
to create individual strains of each subtype.

One would assume that this mutation process would continue indefinitely. But this has not been the case.
In fact, only a small number of mutations give the virus an advantage and are therefore retained in the HIV genome.
HIV has to retain certain characteristics if it is to remain effective. Thatís why we believe there are a limited number
of subtypes and strains. Although new minor subtypes have been identified,
no new major ones have been discovered in more than 15 years.