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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Broad immunogenicity of a multigene, multiclade HIV-1 DNA vaccine boosted with heterologous HIV-1 recombinant modified vaccinia virus Ankara
Journal of Infectious Diseases, Volume 198, No. 10, Year 2008
Notification
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Description
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. © 2008 by the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Sandström, Eric G.
Sweden, Stockholm
Karolinska Institutet
Nilsson, Charlotta
Sweden, Stockholm
Karolinska Institutet
Hejdeman, Bo
Sweden, Stockholm
Karolinska Institutet
Bråve, Andreas
Sweden, Stockholm
Karolinska Institutet
Bratt, Göran A.
Sweden, Stockholm
Karolinska Institutet
Robb, Merlin Lee
United States, Silver Spring
Walter Reed Army Institute of Research
Cox, Josephine H.
United States, Silver Spring
Walter Reed Army Institute of Research
United States, Rockville
International Aids Vaccine Initiative
VanCott, Thomas C.
United States, Silver Spring
Walter Reed Army Institute of Research
United States, Kensington
Advanced Bioscience Laboratories, Inc.
Marovich, Mary Anne
United States, Silver Spring
Walter Reed Army Institute of Research
Stout, Richard
United States, Portland
Bioject Inc.
Aboud, Said
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Bakari, Muhammad
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Pallangyo, Kisali J.
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Ljungberg, Karl
Sweden, Stockholm
Karolinska Institutet
Moss, Bernard
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Earl, Patricia
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Michael, Nelson L.
United States, Silver Spring
Walter Reed Army Institute of Research
Birx, Deborah L.
United States, Silver Spring
Walter Reed Army Institute of Research
United States, Atlanta
Centers for Disease Control and Prevention
Mhalu, Frederick S.
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Wahrén, Britta E.
Sweden, Stockholm
Karolinska Institutet
Biberfeld, Gunnel
Sweden, Stockholm
Karolinska Institutet
Edbäck, Ulrika
Sweden, Stockholm
Karolinska Institutet
Engström, Gunnel
Sweden, Stockholm
Karolinska Institutet
Gudmundsdotter, Lindvi
Sweden, Stockholm
Karolinska Institutet
Hansson-Pilainen, Eva
Sweden, Stockholm
Karolinska Institutet
Isaguliants, Maria
Sweden, Stockholm
Karolinska Institutet
Karlén, Katarina
Sweden, Stockholm
Karolinska Institutet
Kjerrström, Anne
Sweden, Stockholm
Karolinska Institutet
Rollman, Erik
Sweden, Stockholm
Karolinska Institutet
Blomberg, Pontus
Sweden, Stockholm
Karolinska Universitetssjukhuset
Ask, Ronny
Sweden, Stockholm
Södersjukhuset
Ekroth, Stefan
Sweden, Stockholm
Södersjukhuset
Eriksson, Lars E.
Sweden, Stockholm
Södersjukhuset
Petz, Inger
Sweden, Stockholm
Södersjukhuset
Reinhard, Karin
Sweden, Stockholm
Södersjukhuset
Statistics
Citations: 166
Authors: 35
Affiliations: 10
Identifiers
Doi:
10.1086/592507
ISSN:
00221899
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Randomised Control Trial