8th International AIDS Conference Amsterdam, Netherlands — July 19-24, 1992

Int Conf AIDS 1992 Jul 19-24; 8:We45 (abstract no. WeA 1000)
Sodroski J, Thali M, Wyatt R, Posner M, Tilley S, Ho D, Robinson J; Dana-Farber Cancer Institute, Boston, MA.

OBJECTIVES: To identify mutants of HIV-1 that escape neutralization by antibodies recognizing conserved elements of the gp120 glycoprotein and to characterize the mechanism of escape.

METHODS: Panels of HIV-1 mutants were screened for ability to be neutralized by monoclonal antibodies that recognize conserved, discontinuous epitopes on the gp120 glycoprotein. Escape mutants were identified and examined for ability to bind the monoclonal antibody. Ability of the monoclonal antibody to compete for CD4 binding of the wild-type or mutant gp120 glycoprotein were examined.

RESULTS: Amino acid changes outside the epitopes of broadly neutralizing antibodies directed against the CD4 binding site can result in escape from neutralization. The binding affinity of the antibodies to the native glycoprotein complex is not necessarily altered by these amino acid changes. The mechanism of action of different neutralizing antibodies can be categorized by the sensitivity of groups of antibodies to particular neutralization escape-related changes.

CONCLUSIONS: HIV-1 can escape the action of neutralization antibodies directed against conserved, discontinuous gp120 epitopes by changing amino acids outside of the epitope. These results have important implications for understanding how antibodies neutralize HIV-1.

Copyright © 1992 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.