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Immunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade neutralizing antibody responses.
Karolinska Cell Therapy Center, Karolinska University Hospital , 141 86 Stockholm , Sweden.
Department of Laboratory Medicine , Clinical Research Center, Karolinska Institutet , SE-141 86 Huddinge , Sweden.
Department of Microbiology , Tumor and Cell Biology, Karolinska Institutet , 171 77 Stockholm , Sweden.
Department of Microbiology , Tumor and Cell Biology, Karolinska Institutet , 171 77 Stockholm , Sweden.
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2017 (English)In: Human Vaccines & Immunotherapeutics, ISSN 2164-5515, E-ISSN 2164-554XArticle in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: Genetic immunization is expected to induce the expression of antigens in a native form. The encoded peptide epitopes are presented on endogenous MHC molecules, mimicking antigen presentation during a viral infection. We have explored the potential of enfuvirtide (T20), a short HIV peptide with antiviral properties, to enhance immune response to HIV antigens. To generate an expression vector, the T20 sequence was cloned into a conventional plasmid, the novel minicircle construct, and a replicon plasmid. In addition, three conventional plasmids that express the envelope of HIV-1 subtypes A, B and C and contain T20 in their gp41 sequences were also tested.

RESULTS: All combinations induced HIV-specific antibodies and cellular responses. The addition of T20 as a peptide and as an expression cassette in the three DNA vectors enhanced antibody responses. The highest anti-HIV-1 Env titers were obtained by the replicon T20 construct. This demonstrates that besides its known antiviral activity, T20 promotes immune responses. We also confirm that the combination of slightly divergent antigens improves immune responses.

CONCLUSIONS: The antiretroviral T20 HIV-1 sequence can be used as an immunogen to elicit binding and neutralizing antibodies against HIV-1. These, or similarly modified gp41 genes/peptides, can be used as priming or boosting components for induction of broadly neutralizing anti-HIV antibodies. Future comparative studies will reveal the optimal mode of T20 administration.

Place, publisher, year, edition, pages
Taylor & Francis, 2017.
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-141185DOI: 10.1080/21645515.2017.1338546PubMedID: 28696158OAI: oai:DiVA.org:liu-141185DiVA: diva2:1144186
Available from: 2017-09-25 Created: 2017-09-25 Last updated: 2017-10-13Bibliographically approved

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The full text will be freely available from 2018-07-11 16:50
Available from 2018-07-11 16:50

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CiteExportLink to record
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Citation style
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