Facts and Issues [International Conference on AIDS (11th: 1996: Vancouver, Canada)]

Immunomodulators
To date, the development of immunomodulators for HIV has not been very successful.
Although a couple of immune globulins, such as Gamimune-N (Bayer), licensed for pediatric
HIV infection; or Rh0 (D) immune globulin (WinRho SD:' Univax Biologics), licensed for
immune thrombocytopenic purpura (ITP) (illness characterised by purple skin patches and
hemorrhages) secondary to HIV infection, few other potentially exciting compounds have
advanced towards the marketplace.
Interferon, produced by the body to fight viral infections, has been synthesised in various
forms and has been used experimentally in HIV therapy An NDA for one form of interferon,
Wellferon'" (GlaxoWellcome), has been submitted for combination use with AZT and ddC.
Interleukin-2, a natural substance produced byT cells that has antiviral effects, has also been
synthesised and is being tested as a therapeutic agent (e.g. Chiron's Proleukin').
Substances called granulocyte or granulocyte-mononuclear colony stimulating factors (G-CSF
or GM-CSF) can accelerate the maturation of stem cells in the bone marrow.These stem
cells produce the immune system's T and B cells, which are often depleted in HIV infection.
Various such drugs have been or are in the process of being developed, such as filgrastim
(Neupogen:Tm Amgen) and sargramostim (Leukine:' Immunex).
Other experimental immunomodulators include:
* HIV immune globulin (HIV-IG:T" North American Biologicals), for the prevention of HIV
infection in infants born to HIV-infected women
* Imreg- ITP (lmreg), an extract from healthy white blood cells, which stimulates
interleukin-2 and interferon production
* Thalidomide (Andrulis)
" Thymopentin (Timunox:T" Immunobiology Research Institute)
Vaccines
A vaccine works by stimulating the immune system to react against the disease agent it has
been designed to combat. It does this by introducing into the body something harmless
which, to the immune system, "looks" like the disease agent. In polio vaccines, for example,
this "something" can be a "killed" polio virus or a live, attenuated (weakened) one.
Vaccines can be given to people to prevent them from acquiring infection (prophylactic)
or can be given to people who are already infected (therapeutic). In the latter situation, the
vaccine is intended to boost the immune system to delay or prevent development to AIDS.
Early vaccines were prepared by killing or weakening ("attenuating") the infectious organism
or extracting some component from it that would produce an immune response in the
body Because of the risks of inoculation of uninfected people, vaccination with "killed" HIV
would be suitable only for boosting the immune reaction of people already infected with the
virus, as is done, for example, with rabies infections. However, modern techniques of genetic
engineering allow researchers to isolate the gene in the infectious agent that produces the
specific component they want and manufacture it in quantityThis method eliminates the
possibility that the vaccine itself will be infectious. In the case of a virus, the components
chosen are often proteins from the outer coat or envelope.
Thus experimental HIV vaccines have used envelope proteins called gpl20 or gpl60 which
bind the virus to its target cells.The idea is to interfere with the virus' entry into the cell.
This works in test-tube experiments but, unfortunately, has not worked with experimental
vaccines with monkeys.This seems to confirm human observation: that although people
infected with HIV produce antibodies, the antibodies eventually fail to protect them against
the progress of the disease. Other vaccines, such as HGP-30 (Viral Technologies), try to mimic
part of the HIV core (centre).Yet others are based on removing the nefgene, a part of the
HIV required for reproduction.