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Krommelbein N.,Johannes Gutenberg University Mainz | Wiebusch L.,Charite - Medical University of Berlin | Schiedner G.,CAP CMV GmbH | Buscher N.,Johannes Gutenberg University Mainz | And 6 more authors.
Viruses | Year: 2016

The human cytomegalovirus (HCMV) replicates to high titers in primary human fibroblast cell cultures. A variety of primary human cells and some tumor-derived cell lines do also support permissive HCMV replication, yet at low levels. Cell lines established by transfection of the transforming functions of adenoviruses have been notoriously resistant to HCMV replication and progeny production. Here, we provide first-time evidence that a permanent cell line immortalized by adenovirus type 5 E1A and E1B (CAP) is supporting the full HCMV replication cycle and is releasing infectious progeny. The CAP cell line had previously been established from amniotic fluid cells which were likely derived from membranes of the developing fetus. These cells can be grown under serum-free conditions. HCMV efficiently penetrated CAP cells, expressed its immediate-early proteins and dispersed restrictive PML-bodies. Viral DNA replication was initiated and viral progeny became detectable by electron microscopy in CAP cells. Furthermore, infectious virus was released from CAP cells, yet to lower levels compared to fibroblasts. Subviral dense bodies were also secreted from CAP cells. The results show that E1A/E1B expression in transformed cells is not generally repressive to HCMV replication and that CAP cells may be a good substrate for dense body based vaccine production. © 2016 by the authors; licensee MDPI, Basel, Switzerland. Source


Walker K.B.,UK National Institute for Biological Standards and Control | Brennan M.J.,1405 Research Boulevard | Ho M.M.,UK National Institute for Biological Standards and Control | Eskola J.,Finnish National Institute for Health and Welfare | And 6 more authors.
Vaccine | Year: 2010

Infection with Mycobacterium tuberculosis continues to be a major public health burden in most developing parts of the world and efforts to develop effective strategies for containing the disease remain a priority. It has long been evident that effective mass vaccination programmes are a cost effective and efficient approach to controlling communicable diseases in a public health setting and tuberculosis (TB) continues to be a major target. One approach with increasing acceptance is based upon on live mycobacterial vaccines, either as recombinant BCG or rationally attenuated M. tuberculosis, thus generating a new live TB vaccine. The Geneva Consensus published in March 2005 set out the opinion on priorities and requirements for developing live mycobacterial vaccines for Phase I trials. In the intervening period much progress has been made in both preclinical and clinical development of new TB vaccines and has provided the impetus for organising the second Geneva Consensus (held at WHO headquarters, April 2009) to discuss issues, including:i.Explore the regulatory requirements for live TB vaccines to enter Phase I trials, in particular those based on attenuated M. tuberculosis. Particular attention was paid to the characterisation and safety package likely to be required, including issues of attenuation, the presence of antibiotic resistance markers in live vaccines and the nature of any attenuated vaccine phenotype.ii.To identify the general criteria for further clinical development from Phase I through to Phase III.iii.Obtain a perspective of the regulatory landscape of developing countries where Phase II and III trials are to be held.iv.Review manufacturing considerations for live TB vaccines and relevance of the WHO and European Pharmacopeia guidelines and requirements for BCG vaccine.v.Consider requirements and associated issues related to the use of these new vaccines within an existing BCG vaccination programme. Source


Patent
Max Planck Gesellschaft zur Foerderung der Wissenschaften e.V. and Vakzine Projekt Management GmbH | Date: 2011-12-21

The invention relates to a recombinant


Patent
Rhein Biotech Gmbh and Vakzine Projekt Management Gmbh | Date: 2012-09-13

The present invention is related to a composition comprising an agent selected from the group comprising HCMV virions, HCMV dense bodies and HCMV NIEP, whereby the composition is capable of elucidating an immune response while the virions, the NIEP and/or the dense bodies being non-fusiogenic.


Patent
Vakzine Projekt Management Gmbh | Date: 2011-09-16

The invention relates to a recombinant vaccine providing protective immunity especially against tuberculosis in human subjects.

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