Session 14Oral Abstract Presentations Immune-Based Therapy Session Day and Time: Wednesday 10 - 11:15 am Presentation Time: 10:15 Room: Auditorium
60 Phase-I Study with a Therapeutic MVA-BN-Nef Vaccine in HIV-1 Infected Patients on HAART E. Harrer1, M. Bäuerle1, B. Ferstl1, P. Chaplin2, B. Petzold2, S. Bergmann1, M. Hamacher1, J. R. Kalden1, D. Willbold3, T. Harrer*1 1Univ of Erlangen, Germany; 2Bavarian Nordic GmbH, Munich, Germany; and 3Heinrich-Heine Univ, Res Ctr, Jülich, Germany
Background: Increasing side effects of HAART have stimulated interest in therapeutic vaccines to boost HIV-specific immunity. However, there is a lack of vaccines which can induce a strong CTL response in HIV+ patients (pts). Therefore, we studied in a phase-I-study the immunogenicity and safety of the MVA-BN vector (Modified Vaccinia Virus Ankara-Bavarian Nordic) expressing the HIV-1 Nef gene (MVA-BN-Nef).
Methods: Fourteen (14) HIV-1+ pts on HAART with suppressed HIV viremia and CD4 > 400 were immunized at wks 0, 4, and 16 with a MVA-BN construct expressing Nef of HIV-LAI. HIV-specific T-cells were monitored by g-IFN ELISpot. HAART was interrupted in all pts 2 wks after the 3rd vaccination.
Results: MVA-BN-Nef was well tolerated except for mild systemic side effects in a few pts ( headache in 4 pts, fever in 1 pt and myalgia in 2 pts). Local inflammation at the injection sites occurred in all pts. Twelve (12) of14 pts showed a significant increase of CD4 counts from baseline to wk 18. HIV-specific T-cells against at least 1 CTL epitope could be detected at baseline in 10/14 pts. After 3 vaccinations recognition of new T-cell epitopes was induced in 10/14 pts. Eight (8) of 14 pts recognized new CTL epitopes, and 3/14 pts developed Nef-specific CD4-cells. A MVA-specific T-cell response could be observed in 3/14 pts at baseline and in all pts after 3 vaccinations. After interruption of HAART viral load became detectable after a median time of 4 wks (range 2-12 wks) reaching a peak of 46,000 viral copies/ml (median, range 8,400-500,000) after a median time of 6 wks (wk 4-22). So far, HAART has been resumed in 5 pts. 9 pts are still without therapy after a median time of 22 wks (wk12-28) with a median viral load of 8,500 (range 850-37,000). HIV-viremia remained below the historic pre-HAART viral load in 5/9 pts.
Conclusions: MVA-BN-Nef proved to be safe and immunogenic in HIV-infected pts on HAART with a CD4 count > 400. The vaccination could not prevent increase of viremia after interruption of HAART, but a lower viremia in comparison to the pre-HAART viral load suggest an improved control of HIV in a subset of pts.
