Persistent immune responses induced by a human immunodeficiency virus dna vaccine delivered in association with electroporation in the skin of nonhuman primates

Frédéric Martinon, Katrin Kaldma, Rein Sikut, Slobodan Çulina, Gabrielle Romain, Mari Tuomela, Maarja Adojaan, Andres Männik, Urve Toots, Toomas Kivisild, Julie Morin, Patricia Brochard, Benoît Delache, Antonella Tripiciano, Fabrizio Ensoli, Ioana Stanescu, Roger Le Grand, Mart Ustav

Research output: Contribution to journalArticle

Abstract

Strategies to improve vaccine efficacy are still required, especially in the case of chronic infections, including human immunodeficiency virus (HIV). DNA vaccines have potential advantages over conventional vaccines; however, low immunological efficacy has been demonstrated in many experiments involving large animals and in clinical trials. To improve the immunogenicity of DNA vaccines, we have designed a plasmid vector exploiting the binding capacity of the bovine papillomavirus E2 protein and we have used electroporation (EP) to increase DNA uptake after intradermal inoculation. We demonstrated, in nonhuman primates (NHPs), efficient induction of anti-HIV immunity with an improved DNA vaccine vector encoding an artificial fusion protein, consisting of several proteins and selected epitopes from HIV-1. We show that a DNA vaccine delivery method combining intradermal injection and noninvasive EP dramatically increased expression of the vaccine antigen selectively in the epidermis, and our observations strongly suggest the involvement of Langerhans cells in the strength and quality of the anti-HIV immune response. Although the humoral responses to the vaccine were transient, the cellular responses were exceptionally robust and persisted, at high levels, more than 2 years after the last vaccine boost. The immune responses were characterized by the induction of significant proportions of T cells producing both interferon-γ and interleukin-2 cytokines, in both subpopulations, CD4+ and CD8+. This strategy is an attractive approach for vaccination in humans because of its high efficacy and the possible use of newly developed devices for EP.

Original languageEnglish
Pages (from-to)1291-1307
Number of pages17
JournalHuman Gene Therapy
Volume20
Issue number11
DOIs
Publication statusPublished - Nov 1 2009

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Medicine(all)

Cite this

Martinon, F., Kaldma, K., Sikut, R., Çulina, S., Romain, G., Tuomela, M., Adojaan, M., Männik, A., Toots, U., Kivisild, T., Morin, J., Brochard, P., Delache, B., Tripiciano, A., Ensoli, F., Stanescu, I., Le Grand, R., & Ustav, M. (2009). Persistent immune responses induced by a human immunodeficiency virus dna vaccine delivered in association with electroporation in the skin of nonhuman primates. Human Gene Therapy, 20(11), 1291-1307. https://doi.org/10.1089/hum.2009.044