February 13, 2003
This was a difficult-to-understand and lengthy presentation by George Shaw which partly brought the often maligned HIV neutralizing antibodies (Nab) out of the shadows. Current thinking about immune control of HIV has focused on cytotoxic T-lymphocytes (cellular immunity) as the key factor. There has been little support for the view that Nab can play a pivotal role in HIV control. Dr. Shaw detailed several cases of primary infection where a complex set of assays were utilized to assess for the presence and activity of Nab. He presented data suggesting there are Nab that evolve that are potent enough to apply a significant selection pressure on HIV replication. Those Nab were detected as early as 72 days and reached titers (50 percent inhibitory levels = IC50) as high as 1:2,500 by seven months.
The really interesting part of the talk involved the possible mechanism for the subsequent viral escape wherein up to 100-fold change in IC50 was documented. Mutations in the env gene that appeared during the viral escape were not located in the previously described neutralization epitopes. The hypothesis Dr. Shaw put forth was that glycosylation is a key player and that a "glycan shield" serves to protect the virus from the attack of Nab. Data was provided that suggests the mutations that were tracked involve regions involved with glycan binding but not the binding of Nab to receptor sites. One key impression from the series of presentations in this symposia is that our understanding of the immune system is still very limited and that much basic work needs to be done if the immune system is to be manipulated to better control viral replication.
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