Broad Immunogenicity of a Multigene, Multiclade HIV-1 DNA Vaccine Boosted with Heterologous HIV-1 Recombinant Modified Vaccinia Virus Ankara

• Published in: The Journal of infectious diseases Vol. 198; no. 10; pp. 1482 - 1490
• Main 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, Biberfeld, Gunnel
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.11.2008; University of Chicago Press
• Subjects: Adult; AIDS; AIDS vaccines; AIDS Vaccines - administration & dosage; AIDS Vaccines - adverse effects; AIDS Vaccines - immunology; AIDS Vaccines - standards; Antibody Formation - immunology; Biological and medical sciences; DNA; Female; Fundamental and applied biological sciences. Psychology; Genetic Vectors - genetics; Genetic Vectors - immunology; HIV; HIV 1; HIV Infections - prevention & control; HIV-1 - genetics; HIV-1 - immunology; HIV/AIDS; Human immunodeficiency virus 1; Humans; Immune response; Infectious diseases; Injections; Male; Medical sciences; Medicin och hälsovetenskap; Microbiology; Middle Aged; Miscellaneous; T lymphocytes; T-Lymphocytes - immunology; Vaccination; Vaccines, DNA - adverse effects; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Vaccines, DNA - standards; Vaccinia virus; Vaccinia virus - genetics; Vaccinia virus - immunology; Virology; Young Adult; Virus; Infection; Immunogenicity; Microbiology; HIV-1 virus; Viral disease; Retroviridae; Human immunodeficiency virus; Genetic vaccine; Lentivirus; Vaccinia
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1086/592507

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 4 mg 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.