Experimental Vaccinology team (EXPVACC/LEV)

(for a list of the members of this research team, click here)

Laboratory for Experimental Vaccinology (EXPVACC/LEV)

The laboratory is based on vaccine technology which drastically improves vaccine induced immunity against cancers and infections. This technology is currently being developed clinically against a selection of infectious diseases through collaboration with an Italien Biotech company. A range of oncological indications as well of the infections caused by HIV, CMV and human papillomaviruses are however excepted from this evaluation.

The collected focus areas for the laboratory are briefly described below:

Science

The technology base of the lab will be control of adenovirus vectors and adenovirus vector induced immune responses. Understanding the mechanisms of adenovirus induced immunity would allow a specific targeting of induced immunity to the specific challenges associated with each disease indication.

The approach can be considered as gain-of-function, and is analogous to transgenic technologies that are in turn supplemented by knock-out technologies were functions are taken away. However, compared to the classical immunological tool-box our approach are much more specific as only the vaccine vector, and not the whole animal, are being manipulated for the studies. This also leads to a high degree of clinical relevance as we are working directly on improving state-of-the-art medical technology. As a supplement to vaccine vector manipulation, the Danish research council will also be asked to fund a series of studies were models are being created to selectively mark and eliminate specific immune response cell types associated with adenovirus vectored immunity. This approach can be seen as a more classical loss-of-function approach, but it has an unprecedented level of precision.

Clinical relevance

Validated approaches to influence vaccine induced immune responses should be tested in simple cancer and virus infectious models in mice such as melanoma cell lines and the LCMV and the --herpesvirus infection models. This approach will ensure that a few people on the staff can sufficiently train students and they can in turn contribute with reliable knowledge. Approaches that are successful in the simple mouse models should then subsequently be evaluated in more human like disease models. These represent with significant financial and logistic differences and are described below:

Cancer

The laboratory will establish a competence in clinically relevant carcinogen and spontaneous tumor models in rodents. This is realistic within established budgets and can be supplemented by established external collaborations to test new immune response phenotypes and results in the relatively affordable cynomolgus macaque model

Human immunodeficiency virus (HIV)

These experiments can only be executed in a meaningful way on larger grants sufficient for both experimental and control arm vaccination and challenge experiments. Such a grant has been granted to evaluate the current technology in rhesus macaque monkeys against SIV, and the European Research Council are being sought for actual year-long development program.

Human papilloma virus (HPV)

Protection against viral infection can be tested in rabbits and such a study is funded for 2012. Follow-up studies in primates will also be relevant and it is assumed that larger grants for this purpose will be sougt from the Danish cancer society, Bill and Melinda gates foundation and others. The perspective is to develop a vaccine which can eradicate infection with the majority of the oncogenic HPV's.

Clinical development

The EXPVACC/LEV team seeks to contribute to larger international projects on the clinical development of its associated technologies. This is motivated both by a desire to further the clinical application of the technologies and to establish the experience with such projects for future clinical application of the laboratory's own scenarios and concepts.

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For general information about the EXPVACC/LEV team, please contact Peter Johs. Holst