Binding of Potent Neutralizing Antibody to HIV Hints at New Vaccine Targets (GenEngNews) 
Analysis of how a recently identified broadly neutralizing antibody (bnMab) binds to HIV has uncovered a potential target for vaccine development. The antibody, PGT 128, is one of a number isolated from HIV-infected patients by a team led by researchers at the Scripps Research Institute’s IAVI Neutralizing Antibody Center. Of the series of PGT antibodies isolated, PGT 128 is the most broadly neutralizing, and is capable of neutralizing over 70% of globally circulating viruses.
However, what appears to make PGT 128 so much more potent than other recently described anti-HIV bnMabs relates to the way the antibody penetrates through a gap in the glycan shield that protects the viral envelope, and binds to two conserve glycans, as well as a beta-strand segment on the V3 loop of the gp120 envelope protein. This triple binding appears to cross-link Env trimer spikes on the viral coat, and prevent it from infecting cells, claim Dennis R. Burton, Ph.D., Ian A. Wilson, Ph.D., and colleagues. Their findings are reported in Science Express in a paper titled “A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield.”
PGT 128 is one of six bnMAbs (PGTs 125–128, 130–131) isolated by the Scripps-led researchers. The PGT antibodies bind specifically to the Man8/9 glycans on gp120, and potently neutralize across HIV clades, indicating that they may provide protection at relatively low serum concentrations, and the epitopes to which they bind might therefore represent promising vaccine targets. The team’s interest in PGT 128, particularly, arose because the antibody had the broadest neutralizing capability of all the PGT nbMabs, and demonstrates potency that is about an order of magnitude greater than that of other recently described bnMabs, including PG9, PG16, VRC01, and VRCPG04. They therefore carried out crystallization studies to identify the specific binding epitopes for PGT 128.
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Complete article at Gen Eng News : http://bit.ly/mZqL7f
