HIV: The Search For A Vaccine
Uploaded by bavick0 on Nov 19, 2000
In 1985, over 10,000 cases of AIDS were reported worldwide (White and Fenner 1986). Just over a decade later, in 1998, the Global AIDS Policy Coalition estimated that 30.6 million people were infected with HIV worldwide. It has also been projected that by the year 2000, between 40 and 70 million adults will be infected with HIV (New Generation Vaccines 1997). Over 90% of all HIV-1 infected individuals live in developing nations: 50% in Southeast Asia and 40% in sub-Saharan Africa. However, even with all of these alarming statistics and projections, there is hope for the future of humanity. This hope is a potential anti-AIDS vaccine. An anti-AIDS vaccine is the best bet. Among other factors, the large costs associated with therapeutic drugs do not allow many AIDS patients receive them. This is especially true in the developing nations, constituting over 90% of all HIV infections worldwide (Bloom 1995).
Before discussing the development of a potential vaccine, it is imperative to briefly discuss characteristics of HIV itself and also the immune system that these vaccines would target.
HIV, a retrovirus from the Lentivirus subfamily, contains ssRNA nucleic acid. Some of its other characteristics include: an icosahedron capsid, various enzymes (including reverse transcriptase), and envelope with the glycoproteins gp 120, gp 41, and gp160. The genes of HIV-1 can be placed into 3 general categories: structural, regulatory, and accessory genes. The structural genes include gag, pol, and env. The regulatory genes include tat and rev. The accessory genes are nef, vpr, vpu, and vif (Vaccines 1999).
There are two major branches to the immune system in primates: a humoral or adaptive branch and a cell-mediated or innate branch. The cell-mediated immune response operates through MHC I via CD8+ (cytotoxic T cells). Antibodies are not secreted through this branch of the immune system, and the cell-mediated immune response generally targets viruses and other intracellular antigens. The humoral immune response operates through MHC II via CD4+ (helper T cells). The humoral branch secretes antibodies, which generally target extracellular antigens like bacteria and fungi.
There are many obstacles in the way of HIV vaccine development. First, since HIV often mutates its surface glycoprotein (gp120), it has many strains, and the immune response cannot target all of the possible strains. The genetic diversity among HIV-1 strains is also do to an error-prone reverse transcriptase enzyme, as well as recombination. The second obstacle is the lack of an inexpensive,...