Broad immunogenicity of a multigene, multiclade HIV-1 DNA vaccine boosted with heterologous HIV-1 recombinant modified vaccinia virus Ankara

Eric Sandström*, Charlotta Nilsson, Bo Hejdeman, Andreas Bråve, Göran Bratt, Merlin Robb, Josephine Cox, Thomas VanCott, Mary Marovich, Richard Stout, Said Aboud, Muhammad Bakari, Kisali Pallangyo, Karl Ljungberg, Bernard Moss, Patricia Earl, Nelson Michael, Deborah Birx, Fred Mhalu, Britta WahrenGunnel Biberfeld, Ulrika Edbäck, Gunnel Engström, Lindvi Gudmundsdotter, Eva Hansson-Pilainen, Maria Isaguliants, Katarina Karlén, Anne Kjerrström, Erik Rollman, Pontus Blomberg, Ronny Ask, Stefan Ekroth, Lars Eriksson, Inger Petz, Karin Reinhard

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


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 gag A and 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.

Original languageEnglish
Pages (from-to)1482-1490
Number of pages9
JournalJournal of Infectious Diseases
Issue number10
StatePublished - 15 Nov 2008
Externally publishedYes


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