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The induction of potent virus-specific immune responses at mucosal surfaces where virus transmission occurs is a major challenge for vaccination strategies. In the case of influenza vaccination, this has been achieved only by intranasal delivery of live-attenuated vaccines that otherwise pose safety problems. Here, we demonstrate that potent mucosal and systemic immune responses, both cellular and humoral, are induced by intranasal immunization using formulated DNA. We show that formulation with the DNA carrier polyethylenimine (PEI) improved by a 1,000-fold the efficiency of gene transfer in the respiratory track following intranasal administration of luciferase-coding DNA. Using PEI formulation, intranasal vaccination with DNA-encoding hemagglutinin (HA) from influenza A H5N1 or (H1N1)2009 viruses induced high levels of HA-specific immunoglobulin A (IgA) antibodies that were detected in bronchoalveolar lavages (BALs) and the serum. No mucosal responses could be detected after parenteral or intranasal immunization with naked-DNA. Furthermore, intranasal DNA vaccination with HA from a given H5N1 virus elicited full protection against the parental strain and partial cross-protection against a distinct highly pathogenic H5N1 strain that could be improved by adding neuraminidase (NA) DNA plasmids. Our observations warrant further investigation of intranasal DNA as an effective vaccination route. [ABSTRACT FROM AUTHOR]

Replication-defective vectors based on murine oncoretroviruses were the first gene transfer vectors to be used in successful gene therapies. Despite this achievement, they have two major drawbacks: insufficient efficacy for in vivo gene transfer and insertional mutagenesis. Attempts to overcome these problems have led to two retroviral vector designs of principally opposite character: replication-competent vectors transducing largely intact genomes and genome-free vectors. Replication-competent retroviral vectors have achieved dramatically improved efficacy for in vivo cancer gene therapy and genome-free retroviral vectors expressing different kinds of antigens have proven excellent as immunogens. Current developments aim to improve the safety of the replication-competent vectors and to augment the production efficiency of the genome-free vectors by expression from heterologous viral or non-viral vectors. Together with the continuous advances of classical defective retroviral vectors for ex vivo gene therapy, these developments illustrate that, due to their tremendous design versatility, retroviral vectors remain important vectors for gene therapy applications.Molecular Therapy (2007) 15, 457–466. doi:10.1038/sj.mt.6300054; published online 23 January 2007 [ABSTRACT FROM AUTHOR]