Thursday, May 26, 2011

HIV antibody production

To exploit the immune response and the natural system of neutralizing or killing a virus and preventing infection, researchers develop antigens that stimulate the human body to make the antibodies that are most efficient and effective at achieving the intended goals.

For HIV, though, this has been difficult because the surface antigens of HIV vary broadly among infected individuals. A solution to this problem is thought to exist with broadly neutralizing antibodies, naturally occurring human antibodies against relatively constant antigens on the surface of the HIV virion.

When a pathogen or foreign agent enters the human body, the immune system responds in both a broad and specific manner. The human immunodeficiency virus (HIV), the pathogen that causes AIDS, is no exception. The specific immune response involves the processing of the pathogen and presentation of its proteins, or antigens, by specialized immune cells (macrophages and dendritic cells) to other immune cells, one type of which, specifically B cells, are then activated to genetically rearrange and produce antibodies specific to the viral proteins. Antibodies are simply specialized proteins that are produced on an as needed basis under normal circumstances. When an antibody comes into contact with an antigen, usually on the cell or pathogen surface because of accessibility, it binds and causes the pathogen to either be neutralized or destroyed.

Vaccines are a method of artificially stimulating antibody production by exposing the immune system to antigens prior to infection. The human body produces antibodies specific to the antigens or strain with which it is infected. For HIV, this specificity makes vaccination thus far troublesome as the surface antigens of HIV vary broadly among infected individuals. A solution to this problem is thought to exist with broadly neutralizing antibodies, naturally occurring human antibodies against relatively constant antigens on the surface of the HIV virion. These consistent proteins are involved in the infectivity of HIV – the CD4 binding site (glycoprotein gp120) that allows the virus to bind T cells and gp41, the surface protein involved in HIV envelope and cell membrane fusion and viral entry.

To exploit the immune response and this natural system of neutralizing HIV and preventing infection, researchers develop antigens that stimulate the human body to make the antibodies that are most efficient and effective at achieving the intended goals. The most promising method of making HIV antibody is thought to involve creating a vaccine with components that mimic the HIV glycoproteins involved in CD4 recognition and binding – corresponding to the broadly neutralizing antibodies VRC01 and VRC02, which are reported to prevent 90 percent of global HIV strains from infecting human cells in the lab (work by the NIH). The previous most promising vaccine candidate was found in clinical trials to only benefit less than one-third of individuals, which does not meet the goals of vaccination. The discovery of the VRC antibodies is hoped to further advance work on a vaccine that will stimulate the human body to make HIV antibody effectively and in a manner that prevents infection with most, if not all, strains of the virus.

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