Experiment Table CD4+ T lymphocyte counts and viral RNA Results Tetramer Staining Results Neutralizing Antibody Assays Results Viral Sequencing Results Peptide-binding Assays Results ELISPOT assays Results Conclusion   Navigation Home Methods Results Conclusion Quiz Links

Conclusions    This study demonstrates that as little as a single nucleotide mutation, occurring at a sensitive location, can precipitate failure of a vaccine and viral escape leading to increased viral replication, a decline in CD4 levels, symptomatic AIDS, and eventual death. The critical location where the mutation occurred that allowed viral escape caused an amino acid substitution at residue 182 of the gag protein. This mutation resulted in the alteration of the p11C epitope such that CD8 T-lymphocytes no longer recognized the epitope. The selective advantage this mutation gave allowed for the proliferation of clones containing that mutation which led to the eventual failure of this vaccine. The weak response by monkey 798 to the mutant p11C demonstrates the failure of the CD8 cells to recognize this mutant due to the structural change of the epitope that it elicited resulted in a selective advantage and viral escape. The greatest concern comes from the ease with which viral escape was acheived, the result of a single nucleotide mutation.    NEXT