There are no mucosal adjuvant formulations licensed for human use, despite protection against many mucosally-transmitted infections probably requiring immunity at the site of pathogen entry1. Polyethyleneimines (PEI) are organic polycations used as nucleic acid transfection reagents in vitro, and gene and DNA vaccine delivery vehicles in vivo2, 3. Here we show that PEI has unexpected and unusually potent mucosal adjuvant activity in conjunction with viral subunit glycoprotein antigens. Single intranasal administration of influenza HA or HSV-2 gD with PEI elicited robust protection from otherwise lethal infection, and was superior to existing experimental mucosal adjuvants. PEI formed nanoscale complexes with antigen that were taken up by antigen presenting cells in vitro and in vivo, promoted DC trafficking to draining lymph nodes and induced non-proinflammatory cytokine responses. PEI adjuvanticity required release of host dsDNA that triggered Irf-3-dependent signaling. PEI therefore merits further investigation as a mucosal adjuvant for human use.
Polyethyleneimine (PEI) is an organic polycation used extensively as a gene and DNA vaccine delivery reagent. Although the DNA targeting activity of PEI is well documented, its immune activating activity is not. We recently reported that PEI has robust mucosal adjuvanticity when administered intranasally with glycoprotein antigens. Here, we show that PEI has strong immune activating activity after systemic delivery. PEI administered subcutaneously with viral glycoprotein (HIV-1 gp140) enhanced antigen-specific serum IgG production in the context of mixed Th1/Th2-type immunity. PEI elicited higher titers of both antigen binding and neutralizing antibodies than alum in mice and rabbits and induced an increased proportion of antibodies reactive with native antigen. In an intraperitoneal model, PEI recruited neutrophils followed by monocytes to the site of administration and enhanced antigen uptake by antigen-presenting cells. The Th bias was modulated by PEI activation of the Nlrp3 inflammasome; however its global adjuvanticity was unchanged in Nlrp3-deficient mice. When coformulated with CpG oligodeoxynucleotides, PEI adjuvant potency was synergistically increased and biased toward a Th1-type immune profile. Taken together, these data support the use of PEI as a versatile systemic adjuvant platform with particular utility for induction of secondary structure-reactive antibodies against glycoprotein antigens.
Introduction: Technology transfer aims at supporting the transfer of results from software engineering research from academia to industrial application.Objective: This paper reports on the current state of technology transfer in software engineering.Method: We conducted a systematic literature review, in which we investigated 3070 papers. We identified in total 70 relevant papers, which were subject of a detailed analysis.Results: Many different approaches are proposed to foster technology transfer in software engineering. The majority of these approaches suggest direct collaboration between industry and academia or teaching new technologies in industrial training or university education. In addition, a considerable number of experience reports on technology transfer exist. Hence, a multitude of best practices, success stories, and lessons learned is reported. Among others, empirical evidence, maturity, and adaptability of the technology seem important preconditions for successful transfer, while social and organizational factors seem important barriers to successful technology transfer.Conclusion: Our findings can aid software engineering researchers in determining how best to support the transfer of their research results into practice. Furthermore, analysis of the literature also revealed that no reports exist on the combination of various technology transfer approaches, which could increase advantages of existing approaches while reducing their disadvantages. KEYWORDS software engineering, systematic literature review, technology transfer 1 | BACKGROUND AND MOTIVATION Software engineering research aims at solving real-world problems (cf Wieringa 1 ) and demands the evaluation of a proposed solution in an industrial setting (cf Basili 2 and Salman et al 3 ). However, there is often still a gap between academic solution proposals and industrial needs, and for many results from software engineering research, it takes a long time to have an impact on software engineering practices. 4 This is not only due to the fact that novel results from academic research are often unknown to practitioners but also that those research results are often not directly applicable to industry. 5To close this gap, software engineering research also deals with technology transfer itself (cf Pfleeger 6 ). Technology transfer aims at supporting the transfer of research results from academia to practice and is thus of interest to many scientific disciplines (cf, eg, Teece 7 ). While some challenges remain the same regardless of the technology to be transferred, others are particular to the software engineering field, as software engineering technologies typically evolve in a short time and thus the state of the art constantly changes (cf Boehm 8 and Finkelstein and Kramer 9 ).There exists a plethora of proposed solution approaches to foster technology transfer in software engineering as well as experience reports on successful technology transfer projects. Nevertheless, there is a need to support researchers in identifying proper technol...
Novel, exciting intervention strategies to prevent infection with HIV have been tested in the past year, and the field is rapidly evolving. EUROPRISE is a network of excellence sponsored by the European Commission and concerned with a wide range of activities including integrated developmental research on HIV vaccines and microbicides from discovery to early clinical trials. A central and timely theme of the network is the development of the unique concept of co-usage of vaccines and microbicides. This review, prepared by the PhD students of the network captures much of the research ongoing between the partners. The network is in its 5th year and involves over 50 institutions from 13 European countries together with 3 industrial partners; GSK, Novartis and Sanofi-Pasteur. EUROPRISE is involved in 31 separate world-wide trials of Vaccines and Microbicides including 6 in African countries (Tanzania, Mozambique, South Africa, Kenya, Malawi, Rwanda), and is directly supporting clinical trials including MABGEL, a gp140-hsp70 conjugate trial and HIVIS, vaccine trials in Europe and Africa.
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