TY - JOUR
T1 - Persistent immune responses induced by a human immunodeficiency virus dna vaccine delivered in association with electroporation in the skin of nonhuman primates
AU - Martinon, Frédéric
AU - Kaldma, Katrin
AU - Sikut, Rein
AU - Çulina, Slobodan
AU - Romain, Gabrielle
AU - Tuomela, Mari
AU - Adojaan, Maarja
AU - Männik, Andres
AU - Toots, Urve
AU - Kivisild, Toomas
AU - Morin, Julie
AU - Brochard, Patricia
AU - Delache, Benoît
AU - Tripiciano, Antonella
AU - Ensoli, Fabrizio
AU - Stanescu, Ioana
AU - Le Grand, Roger
AU - Ustav, Mart
PY - 2009/11/1
Y1 - 2009/11/1
N2 - 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.
AB - 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.
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U2 - 10.1089/hum.2009.044
DO - 10.1089/hum.2009.044
M3 - Article
C2 - 19627235
AN - SCOPUS:70449124456
VL - 20
SP - 1291
EP - 1307
JO - Human Gene Therapy
JF - Human Gene Therapy
SN - 1043-0342
IS - 11
ER -