[First exchange of experiences concerning the H1N1 pandemic in Germany 2009/2010: report on a workshop held March 22-23, 2010, in Berlin]. / Erster Erfahrungsaustausch zur H1N1-Pandemie in Deutschland 2009/2010: Bericht über einen Workshop am 22. und 23. März 2010 in Berlin.

In April 2009 the first pandemic of the 21st century developed within a few weeks starting from Mexico. Its first wave reached Germany in autumn 2009 and was responsible for 1.8-3.5 million additional medical consultations. For the public health sector, this pandemic was one of the largest challenges of the last few decades. As a contribution to broader evaluations on national and international level, the Robert Koch Institute invited representatives from different professions involved in the pandemic response to participate in a workshop on 22-23 March 2010. This workshop was structured in short presentations, group work, and plenary discussions. Main experiences were that (a) pandemic preparedness was helpful, (b) the early warning systems were reliable, (c) vaccines were available within a few months, however, in limited amounts. Need for improvement was discussed for (a) effectiveness of vaccination logistics, (b) mechanisms for the reimbursement of the cost of vaccination, (c) availability of surveillance and monitoring systems, (d) integration of physicians in decision-making processes and health education, and (e) proactive communication strategies. Investments in the above mentioned areas can help to improve public health protection in the future.

Safety of phase I clinical trials with monoclonal antibodies in Germany--the regulatory requirements viewed in the aftermath of the TGN1412 disaster.

This review summarizes scientific, ethical and regulatory aspects of Phase I clinical trials with monoclonal antibodies. The current standard requirements for pre-clinical testing and for clinical study design are presented. The scientific considerations discussed herein are generally applicable, the view on legal requirements for clinical trials refer to the German jurisdiction only. The adverse effects associated with the TGN1412 Phase I trial indicate that the predictive value of pre-clinical animal models requires reevaluation and that, in certain cases, some issues of clinical trial protocols such as dose fixing may need refinement or redesign. Concrete safety measures, which have been proposed as a consequence of the TGN1412 event include introduction of criteria for high-risk antibodies, sequential inclusion of trial participants and implementation of pre-Phase I studies where dose calculation is based on the pre-clinical No Effect Level instead of the No Observed Adverse Effect Level. The recently established European clinical trials database (EUDRACT Database) is a further safety tool to expedite the sharing of relevant information between scientific authorities.

Corf, the Rev/Rex homologue of HTDV/HERV-K, encodes an arginine-rich nuclear localization signal that exerts a trans-dominant phenotype when mutated.

Regulation of nucleo-cytoplasmic export of viral transcripts by a viral protein (Rev/Rex) is a characteristic feature in the replication cycle of complex retroviruses. We recently reported that the endogenous retrovirus family HTDV/HERV-K encodes a protein, Corf, that is a cellular Counterpart of Rev/Rex function and thus a new component of nucleo-cytoplasmic pathways. In HTDV/HERV-K-expressing cells, Corf is localized within the nucleoli. Here we describe the nuclear localization signal (NLS) of the Corf protein. Mutations in the NLS lead to cytoplasmic accumulation of the mutated protein and abrogate Corf function in a trans-dominant way.

Expression of the human endogenous retrovirus HTDV/HERV-K is enhanced by cellular transcription factor YY1.

The human endogenous retrovirus HTDV/HERV-K, which resides in moderate copy numbers in the human genome, is expressed in a cell-type-specific manner, predominantly in teratocarcinoma cells. We have analyzed the regulatory potential of the 5' enhancer of the HERV-K long terminal repeat. Protein extracts of HERV-K-expressing teratocarcinoma cell lines (GH and Tera2) and nonexpressing HeLa and HepG2 cells form different protein complexes on the enhancer sequence as detected by electrophoretic mobility shift assays (EMSA). Using competition EMSAs, DNase I footprinting, and supershift experiments, we localized the binding site of these complexes to a 20-bp sequence within the enhancer and showed that the transcription factor YY1 is one component of the HERV-K enhancer complex. Replacement of the YY1 binding site with unrelated sequences reduced expression of the luciferase gene as a reporter in transient-transfection assays.