The neutralizing epitope ELDKWA on HIV-1 gp41: Genetic variability and antigenicity

Viral evasion through mutations of neutralizing epitopes is a major challenge to AIDS vaccine development and clinical therapy. In this study, we analyzed the genetic variability of principal neutralizing epitope ELDKWA among 5393 HIV isolates in the HIV sequence database (http://www.hiv.lanl.gov). It has been found that six out of seven frequent variants were able to cause the invalidation of famous neutralizing MAb 2F5. Moreover, escape mutations K665S and K665E, often observed in C-subtype and O-group strains, respectively, were reported more frequently in recent years. Furthermore, we studied the antigenicity of these variants. Polyclonal antibodies induced by a candidate multi-epitope-vaccine were able to react with the recombinant gp41, respectively, carrying these variants, indicating that "epitope cocktail" strategy is necessary and helpful in vaccine design.