DNA-encoding enzymatically active HIV-1 reverse transcriptase, but not theinactive mutant, confers resistance to experimental HIV-1 challenge

The present study was undertaken to examine the immunogenicity of a single plasmid DNA representing the reverse transcriptase (RT) of HIV-1. Plasmids containing the enzymatically active RT as well as a mutated nonenzymaticall y active RT with nucleotide (nt)-binding motifs of YMDD and YMLL, respectiv ely, were used to immunize mice. Both constructs induced similar good antib ody and T cell responses, with a tendency towards antibody directed to pept ides representing the active and mutated sites. immunized mice were challen ged with a murine pseudotype HIV-1/MuLV infected spleen cells. Seven out of 10 mice immunized with RT had no recoverable HIV-1, while 10 individuals i mmunized with the RT mutant and all the 18 controls had high levels of reco verable HIV-1. This indicates that mutation of RT reduces the desired immun ogenicity. Copyright (C) 2001 S. Karger AG, Basel.