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Increased Generation of HIV-1 gp120-Reactive CD8(+) T Cells by a DNA Vaccine Construct Encoding the Chemokine CCL3
University of Oslo, Norway Oslo University Hospital, Norway University of Oslo, Norway .
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
University of Oslo, Norway Oslo University Hospital, Norway University of Oslo, Norway .
University of Oslo, Norway Oslo University Hospital, Norway University of Oslo, Norway University of Oslo, Norway .
2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 8, e104814- p.Article in journal (Refereed) Published
Abstract [en]

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.

Place, publisher, year, edition, pages
Public Library of Science , 2014. Vol. 9, no 8, e104814- p.
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-110974DOI: 10.1371/journal.pone.0104814ISI: 000341017000062PubMedID: 25122197OAI: oai:DiVA.org:liu-110974DiVA: diva2:751640
Note

Funding Agencies|Research Council of Norway; Odd Fellow

Available from: 2014-10-01 Created: 2014-10-01 Last updated: 2017-12-05

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Hinkula, Jorma

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CiteExportLink to record
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