Mapping the long genetic road to broadly neutralising antibodies
Richard Jefferys, TAG
Over the past couple of years, several new antibodies capable of neutralizing a broad array of HIV isolates have been discovered.
As mentioned in prior posts about these discoveries, one common feature of these antibodies is that the B cells that produce them have undergone an unusual degree of somatic hypermutation?a process in which the cell’s antibody-producing genetic code is progressively revised in order to increase the affinity of the antibody for its target. The genetic code that the B cell starts out with is called the germline sequence, and it is typically altered by around 5-15% to produce antibodies against common infections, whereas this figure ranges from 19-46% for the broadly neutralising antibodies against HIV that have been identified. Antibodies targeting the part of the HIV envelope that binds to the CD4 receptor, such as the recently discovered VRC01, are at the extreme end of this scale (showing sequence alterations of 40-46%).
In a recent article in Science Express, researchers from the Vaccine Research Center (VRC), the Center for HIV/AIDS Vaccine Immunology (CHAVI) and the International AIDS Vaccine Initiative (IAVI) published the latest results from their collaborative effort to better understand how these antibodies are generated. 
The work involves analyses of mind-boggling numbers of B cell genetic sequences, and identifies several new broadly neutralising antibodies from infected individuals that target HIV’s CD4 binding site. Of potential importance for vaccine design, the B cell sequences that give rise to the antibodies are not uncommon, and although a similarly extensive degree of somatic hypermutation is involved in their generation, it appears that the mutations do not have to be exactly the same to produce structurally similar antibodies.
The researchers are hopeful that these data can be used as a map for guiding the development of broadly neutralising antibodies using vaccines. 
Source: TAG basic science blog (12 August 2011).
- Wu X et al. Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science (11 August 2011). DOI: 10.1126/science.1207532.
- NIAID Press Release: NIH-Led Team Maps Route for Eliciting HIV Neutralizing Antibodies.