Therapeutic vaccination reduces HIV sequence variability

With HIV persisting lifelong in infected persons, therapeutic vaccination is a novel alternative concept to control virus replication. Even though CD8 and CD4 cell responses to such immunizations have been demonstrated, their effects on virus replication are still unclear. In view of this fact, we studied the impact of a therapeutic vaccination with HIV nef deliv- ered by a recombinant modified vaccinia Ankara vector on viral diversity. We investigated HIV sequences de- rived from chronically infected persons before and after therapeutic vaccination. Before immunization the mean SE pairwise variability of patient-derived Nef protein sequences was 0.1527 0.0041. After vaccina- tion the respective value was 0.1249 0.0042, resulting in a significant (P<0.0001) difference between the two time points. The genes vif and 5gag tested in parallel and nef sequences in control persons yielded a constant amino acid sequence variation. The data presented suggest that Nef immunization induced a selective pressure, limiting HIV sequence variability. To our knowledge this is the first report directly linking thera- peutic HIV vaccination to decreasing diversity in pa- tient-derived virus isolates.—Hoffmann, D., Seebach, J., Cosma, A., Goebel, F. D., Strimmer, K., Schatzl, H. M., Erfle, V. Therapeutic vaccination reduces HIV sequence variability. FASEB J. 22, 437- 444 (2008)