Developing a vaccine against the human immunodeficiency virus (HIV) and the acquired immunodeficiency it causes (AIDS) has been difficult because of the high rate of mutation the virion’s envelope glycoproteins undergo. Previous attempts at an HIV vaccine have had disappointing results, protecting only one-third of affected individuals in the most promising clinical trials. However, researchers have identified new antibodies against the virus that may target the most static portions of the virus molecule, opening the door to better vaccine candidates.
HIV Antibody Production
Similar to other pathogens, when HIV enters the human body, the immune system eventually responds in a specific manner. The pathogen is processed and its proteins, or antigens, presented by specialized immune cells to other immune cells, specifically B cells, which then produce antibodies specific to the viral proteins. The antibodies are effective at recognizing the virus in the blood when they are against the cell surface proteins present on the molecule currently in the blood. Antibodies are produced by the body as needed after exposure to the pathogen. These proteins then bind to the pathogen to either neutralize it (reducing its ability to infect a cell) or targeting it for destruction by host systems.
The problem with HIV is the broad range of cell surface proteins expressed by the various strains currently infecting the human population, making the antibodies in one person irrelevant to another person. In addition, the time it takes for the immune system to stimulate antibody production against HIV renders it useless for clearing the body of infection because the virus infects the immune cells produced to destroy the pathogen – the T cells. Preventative antibody production may be the only way the immune response can be helpful against the virus and prevent it from being a life-long burden.
What an HIV Vaccine Would Do
Vaccines are an artificial method of stimulating antibody production by exposing the immune system to antigens, which is effective at preventing infection in most diseases if administered prior to exposure to the real virus. To exploit this natural system, researchers have been attempting to develop antigens that stimulate the human body to make antibodies that are most efficient and effective at neutralizing HIV in the most people. The most promising method of making an HIV vaccine is thought to involve mimicking the HIV glycoproteins involved in CD4 recognition and binding (gp120) or the cofactor involved in viral entry into the host cell (i.e. infection; gp41).
Broadly Neutralizing Antibodies
The National Institutes of Health (NIH) announced in July 2010 that researchers discovered a pair of broadly neutralizing antibodies, which they call VRC01 and VRC02. The antibodies were tested with human cells in a lab to determine whether they prevent HIV infection and were found to be effective against 90 percent of current HIV strains, the most promising find to date. These antibodies are rare but have been isolated from the blood of HIV-positive patients and may be the initial step in creating antigens for use in an HIV vaccine.
VRC01 and VRC02 bind proteins on the cell surface that remain relatively constant among HIV strains, such as gp120. Binding in this manner blocks the CD4 binding site, which prevents infection and essentially neutralizes the virus. Future work will involve studying where and how the antibody binds, which will provide information about the binding habits of HIV, which could aid vaccine component development.
References:
Melly Alazraki, Scientists discover antibodies that could help create AIDS vaccine. Daily Finance July 8, 2010. Accessed July 16, 2010.
National Institutes of Health News. July 8, 2010. Accessed July 16, 2010.
Sun et al. HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodomain region on the viral membrane. Immunity, January 2008.
Alicia Mae Prater - Alicia received her doctorate in Experimental Pathology in 2007. She has been a freelance writer and scientific editor since 2008.
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