We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Broad Immunogenicity of a Multigene, Multiclade HIV-1 DNA Vaccine Boosted with Heterologous HIV-1 Recombinant Modified Vaccinia Virus Ankara.
- Authors
Sandström, Eric; Nilsson, Charlotta; Hejdeman, Bo; Bråve, Andreas; Bratt, Göran; Robb, Merlin; Cox, Josephine; VanCott, Thomas; Marovich, Mary; Stout, Richard; Aboud, Said; Bakari, Muhammad; Pallangyo, Kisali; Ljungberg, Karl; Moss, Bernard; Earl, Patricia; Michael, Nelson; Birx, Deborah; Mhalu, Fred; Wahren, Britta
- Abstract
Background. A human immunodeficiency virus (HIV) vaccine that limits disease and transmission is urgently needed. This clinical trial evaluated the safety and immunogenicity of an HIV vaccine that combines a plasmid-DNA priming vaccine and a modified vaccinia virus Ankara (MVA) boosting vaccine. Methods. Forty healthy volunteers were injected with DNA plasmids containing gp160 of HIV-1 subtypes A, B, and C; rev B; p17/p24 gagAand B, and RTmut B by use of a needle-free injection system. The vaccine was administered intradermally or intramuscularly, with or without recombinant granulocyte macrophage colony-stimulating factor, and boosted with a heterologous MVA containing env, gag, and pol of CRF01A_E. Immune responses were monitored with HIV-specific interferon (IFN)-γ and interleukin (IL)-2 ELISpot and lymphoproliferative assays (LPAs). Results. Vaccine-related adverse events were mild and tolerable. After receipt of the DNA priming vaccine, 11 (30%) of 37 vaccinees had HIV-specific IFN-γ responses. After receipt of the MVA boosting vaccine, ELISpot assays showed that 34 (92%) of 37 vaccinees had HIV-specific IFN-γ responses, 32 (86%) to Gag and 24 (65%) to Env. IFN-γ production was detected in both the CD8+ T cell compartment (5 of 9 selected vaccinees) and the CD4+ T cell compartment (9 of 9). ELISpot results showed that 25 (68%) of 37 vaccinees had a positive IL-2 response and 35 (92%) of 38 had a positive LPA response. Of 38 subjects, a total of 37 (97%) were responders. One milligram of HIV-1 DNA administered intradermally was as effective as 4mg administered intramuscularly in priming for the MVA boosting vaccine. Conclusion. This HIV-DNA priming-MVA boosting approach is safe and highly immunogenic. Trials registration. International Standard Randomised Controlled Trial number: ISRCTN32604572.
- Subjects
HIV infection transmission; HIV; MITOCHONDRIAL DNA abnormalities; HIV-positive persons; NUCLEIC acids; T cells; LENTIVIRUS diseases; ANTIVIRAL agents; VACCINATION
- Publication
Journal of Infectious Diseases, 2008, Vol 198, Issue 10, p1482
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1086/592507