Andreas Bråve Project
Immunization strategies against HIV-1: immunogen design and optimization of vaccine delivery
More than twenty-five years have passed since the identification and isolation of Human Immunodeficiency Virus type 1 (HIV-1). Although there is still no effective vaccine available against the virus, recent results from a phase 3 trial in Thailand have indicated that protective immunity can be achieved by immunization. Due to the intrinsic nature of the virus, classical vaccine approaches, such as inactivated virus vaccines or protein-based vaccines, have failed and researchers are forced to turn to more novel vaccine-strategies, such as gene-based vaccination (e.g. DNA-vaccination). However, DNA vaccines have so far elicited weaker immune responses in humans than anticipated and, in most current clinical trials, plasmid vaccines are used primarily to prime the immune system for a subsequent boost with recombinant protein or a live recombinant attenuated viral vector, such as Modified Vaccinia virus Ankara (MVA) or Adenovirus.
Our vaccine strategy against HIV-1 is to target multiple viral antigens deriving from various subtypes of the virus. The results from our clinical trials, in which HIV DNA plasmids are combined with a recombinant MVA, are encouraging with close to 100% of the volunteers responding against HIV-1 antigens after immunization. We are now developing the next generation of genetic HIV-1 immunogens and also focusing on improving the delivery of the plasmid DNA vaccine by the use of electroporation. In vivo-electroporation is the application of short pulses of electric current immediately after, and at the site of, an injection with a genetic vaccine and we and others have shown that it is possible to significantly augment the subsequent vaccine-specific immune responses using this method. Now, the overall aim is to develop an immunization strategy that will allow plasmid DNA to be used as a stand-alone vaccine modality.
Selected Publications
Andreas Bråve, David Hallengärd, Maria Malm, Vesna Blazevic, Erik Rollman, Ioana Stanescu and Kai Krohn
Combining DNA technologies and different modes of immunization for induction of humoral and cellular anti-HIV-1 immune responses.
Vaccine 27(2), 184, 2009
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 Wahren and Gunnel Biberfeld
Broad Immunogenicity of a Multigene, Multiclade HIV-1 DNA Vaccine Boosted with Heterologous HIV-1 Recombinant Modified Vaccinia Virus Ankara
The Journal of Infectious Diseases 198, 1482, 2008
Andreas Bråve, Andreas Boberg, Lindvi Gudmundsdotter, Erik Rollman, Kristian Hallermalm, Karl Ljungberg, Pontus Blomberg, Richard Stout, Staffan Paulie, Eric Sandström, Gunnel Biberfeld, Patricia Earl, Bernard Moss, Josephine H. Cox and Britta Wahren
A New Multi-clade DNA Prime/Recombinant MVA Boost Vaccine Induces Broad and High Levels of HIV-1-specific CD8+ T-cell and Humoral Responses in Mice
Molecular Therapy 15(9), 1724, 2007