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The Aids Vaccine Research and Development What is HIV? -Human Immunodeficiency Virus that leads to AIDS, Acquired Immunodeficiency Syndrome It is an RNA retrovirus. The RNA enters the cell, and the reverse transcriptase makes DNA out of the RNA. The DNA enters the nucleus as a provirus, and becomes part of the cell’s chromosomal DNA. This DNA can create more viruses that will infect more cells in the body. Damages and destroys the white blood cells that run the body’s Immune system, breaking down its defenses and leaving it open to infections from other diseases. What is the difference between HIV and AIDS? -HIV is the ground state for the virus, infected individuals can live for as much as 10 years without feeling an effect. -AIDS is the later state of the virus, when the CD4+ T cell count drops below 200, in a healthy person it exceeds 1000. How is it Spread? -The HIV virus is carried in blood, semen, vaginal fluid, breast milk and to a far lesser extent saliva -It is spread most commonly through unprotected sex, needle sharing, breastfeeding by an infected parent. -It is a growing epidemic in areas of the world where healthcare and education are underdeveloped. What does it do? The HIV virus targets T Cells in the immune system. These cells protect the body from infection. Our immune system is constantly under attack, a healthy person has no problem warding off most infections. When enough T Cells have been killed, the immune system can no longer function properly. The body is vulnerable to all kinds of diseases and eventually dies due to it’s inability to defend itself against diseases as common as colds. What is the Rate of Infection, and How Many People are Currently infected with it? At the end of 2000, 36.1 million people lived with Aids, 21.8 million are already dead. In Sub-Saharan Africa 10% of adults are infected. The Aids epidemic in Africa has created a generation of orphans, many of whom also become infected. A full course of medication for Aids costs $15,000 a year, more than most developing villages can spend on healthcare for the entire community. Aids is spreading rapidly through Central Asia, partly from the drug trade, and partly from unsafe sexual practices. 95% of all infections are in underdeveloped countries What medications are used to control HIV? The first group are nucleoside reverse transcriptase inhibitors (RT) that stop the virus from replicating itself. Some examples are AZT and ddl, dideoxyinosine. Non-Nucleoside reverse transcriptase drugs include Nevirapine and Delavirdine. These drugs prevent the reverse transcriptase enzyme from being able to change the RNA of the HIV virus into DNA in the cell. Protease inhibitors stop the viral reproduction at an early stage, some examples are ritonavir, saquinivir and nelfinavir. Vaccine Types Most vaccines contain a dead or mostly killed version of a virus. This is not possible in the Aids vaccine, because even a small amount of the virus can be infect the host and kill them. “Sub unit” vaccines contain a small part of the virus, that the immune system can learn to recognize and kill without placing the subject in danger of infection. Immunity The first kind of immunity is antibody immunity, this attacks and kills the virus in the liquid parts of the body. The second kind is cell mediated immunity, which simply kills the infected cells. Vaccine HIV vaccines approaches recombinant protein (gp120) synthetic peptides (V3) naked DNA live-recombinant vectors (viral, bacterial) whole-inactivated virus live-attenuated virus 1 UNAIDS–97098 1 August 1998 Naked Genetic Material in Plasmids These are bacterial plasmids that have a piece of the HIV genetic material in them. They are injected into the cell in an attempt to create immunity. Similar experiments with mice and the influenza virus have shown that immunity is created. The cell learns to recognize and kill the plasmids without being exposed to any harm itself. Recombinant Proteins The envelope for the Aids virus is formed by gp 160, a protein. Gp 120, which is part of gp 160 and gp 160 itself are used to make recombinant subunit vaccines. These are vaccines in which only part of the protein envelope is injected into the subject in order to stimulate antibodies. Whole, Inactivated Virus The virus is injected whole, but dead, in a more traditional form of vaccination, in an attempt to create antibodies to a nonpathonogenic form of the Aids virus. Live, Attenuated Virus The genetic material inside the virus is killed, but the protein envelope remains intact and whole. The virus is then harmless, and the immune system can be trained to recognize and kill the protein shell. Keys To The Vaccine People who are repeatedly exposed, such as prostitutes in developing countries, yet do not develop HIV. People who have long term HIV infections, whose T Cell counts remain high, or have a decrease in T Cells that does not effect their health. Difficulties in Developing a Vaccine Human trials are difficult and the ethics surrounding them are extremely complicated. There are 3 main types of Aids, type M, which has 9 subtypes, type N and type O. Most successful viral vaccines only have to protect against a few forms of the virus. Unless a common type is found, the vaccine would have to be a combination of several viral subgroups. Treatment and Prevention Education-People in underdeveloped countries are being educated about Aids risks. Condoms are being distributed more commonly among high risk groups, such as prostitutes. Aids Vaccine is being developed In an effort to make them affordable, Aids drugs are being made generically. Political leaders in underdeveloped countries are starting to speak out about the epidemic. Bibliography HIV Vaccine Handbook: Community Perspectives on Participating in Research, Advocacy, and Progress, edited by Bill Snow. Washington, D.C., AIDS Vaccine Advocacy Coalition, 1999. David Gold, Sam Avrett, HIV Vaccines are moving slowly into human trials, 1999 The Village Voice, Aids in Africa, 1999, by Mark Schoofs National Institute of Health, National Institute of Allergy and Infectious diseases, Aids Vaccine. UNAIDS, United Nations Aids Initiative International Aids Vaccine Initiative Research Newsletter., Feb 14, 2002, Berna Biotech teams with IAVI, Gallo lab, Uganda to test AIDS vaccine designed for developing countries Aids Treatment news, Aids.org. Information on Medication available. WHO, World Health Organization, World Health Report 2001.