AIDSWEEKLY Plus; Monday, June 9, 2003
Michael Greer, Senior Medical Writer

"The ability to induce broadly neutralizing antibodies should be a key component of any forthcoming vaccine" against HIV, noted Ralph Pantophlet and colleagues at the Scripps Research Institute in La Jolla, California. However, "one potential vaccine candidate, monomeric gp120, has generally failed to elicit such antibodies."

A hyperglycosylated gp120 mutant preferentially bound to a broadly neutralizing antibody, and could form the basis for a more effective vaccine, Pantophlet and coauthors reported.

The researchers had previously found that alanine substitutions around gp120's "Phe-43 cavity" improved binding of the broadly neutralizing antibody b12. These mutations also inhibited binding of weakly neutralizing CD4-binding site antibodies, according to the report.

Seeking to build on these results, the scientists added a series of N-glycosylation motifs to key positions in the gp120 genome. A gp120 mutant with these extra motifs and the previously described alanine substitutions maintained b12 binding, but was unable to bind antibodies with little or no neutralizing activity, test results indicated.

However, this mutant also bound antibodies to the C1 and C5 regions; removing residues in these regions prevented efficient binding of these antibodies but also impaired b12 binding (Hyperglycosylated mutants of human immunodeficiency virus (HIV) type 1 monomeric gp120 as novel antigens for HIV vaccine design. J Virol. 2003 May;77(10):5889-901.

"The hyperglycosylated mutant and its analogues described here are novel antigens that may provide a new approach to eliciting antibodies with b12-like neutralizing properties," Pantophlet and colleagues concluded.

The corresponding author for this report is Dennis R. Burton, Scripps Research Institute, Department of Immunology (IMM2), 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA. E-mail: burton@scripps.edu.

Key points reported in this study include:

• A hyperglycosylated HIV gp120 mutant may induce more effective humoral responses than the wild-type protein

• A recombinant form of gp120 showed improved binding of the broadly neutralizing antibody b12

• This gp120 mutant also demonstrated reduced binding of antibodies with little or no neutralizing activity

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Pantophlet R, Wilson IA, Burton DR. "Hyperglycosylated mutants of human immunodeficiency virus (HIV) type 1 monomeric gp120 as novel antigens for HIV vaccine design", J Virol. 2003 May;77(10):5889-901.

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