Summary:

With support from two successive EU-sponsored consortia, within the Fifth Framework Programme, an in vivo targeting approach has been developed for dendritic cells (DC), which is applicable to protein vaccines, DNA vaccines and viral vector vaccines. Given the urgent need for an HIV vaccine, the potential of this innovative vaccine approach will be evaluated as quickly as possible. Therefore, the aims of the current application of the consortium are to determine the efficacy of dendritic cell-targeted protein-, DNA-, and viral vector vaccines in animal models of HIV/AIDS, and to understand the requirements for and mechanisms of protection.

Background:

Safe, effective and affordable vaccines are needed that elicit the broadest and most robust immune responses against HIV. With the work of this project, these important questions of vaccine research will be addressed. It is planned to use an innovative vaccine developed by the consortium in the macaque model for AIDS. Critical to the success of this innovative vaccine should be its capacity to enhance uptake and presentation of antigens by dendritic cells, which will be analysed by proof of concept studies by the consortium. The project’s strategy to enhance antigen uptake and presentation by DCs can be applied to protein vaccines, peptide vaccines, DNA vaccines and viral vector vaccines, thus providing a broad vaccination platform.

Aim:

The consortium’s mission is to provide a novel HIV vaccine strategy for safety and efficacy studies in humans by the end of the project. Therefore, the scientific and technological objectives of the project are to determine the following for dendritic cell targeted protein, DNA, and viral vector vaccines:

1. the DC targeting efficacy
2. the immunogenicity
3. the efficacy of different adjuvants
4. the protective properties in the HIV-1/MuLV and SIV macaque model.

Based on these results, the mechanisms of protection will be investigated.

Expected results:

Given the striking positive results in rodent models, this strategy certainly has the potential to be effective and confront the global emergency caused by the spreading HIV epidemic.

Potential applications:

Results from this research effort could lead to the development of a prophylactic or therapeutic HIV/AIDS vaccine. The dendritic cell-targeted vaccine approach could also be useful for the development of vaccines against other infectious diseases and cancer.

Coordinator:

Partners:

Nº	Principal Scientific Participants	Official Address	Other Information
2	Ralph Steinman	The Rockefeller University Laboratory of Cellular Physiology and Immunology 1230 York Avenue 10021-6399 New York, N.Y. United States of America	Tel: +1 212 327 8106 Fax: +1 212 327 8875 E-mail: steinman@rockefeller.edu
3	Britta Wahren	Swedish Institute for Infectious Disease Control Department of Virology Nobels väg 18 SE-171 82 Stockholm Sweden	Tel: +46 8 4572630 Fax: +46 8 337272 E-mail: britta.wahren@smi.ki.se
4	Christiane Stahl-Hennig	Deutsches Primatenzentrum Department of Virology and Immunology Kellnerweg 4 DE-37077 Göttingen Germany	Tel: +49 551 3851154 Fax: +49 551 3851184 E-mail: stahlh@dpz.gwdg.de
5	Ralf Ignatius	Abt. Med. Mikrobiologie u. Infektionsimmunologie Hindenburgdamm 27 DE-12203 Berlin Germany	Tel: +49 30 84453620 Fax: +49 30 84453830 E-mail: ralf.ignatius@charite.de
6	Paul Racz	Bernhard-Nocht-Institute for Tropical Medicine Department of Pathology Bernhard-Nocht-Str. 74 DE-20359 Hamburg Germany	Tel: +49 40 42818499 Fax: +49 40 42818544 E-mail: racz@bni.uni-hamburg.de
7	Mariagrazia Uggucioni	Institute for Research in Biomedicine Via Vincenzo 6 CH-6500 Bellinzona Switzerland	Tel: +41 91 8200300 Fax: +41 91 8200305 E-mail: mariagrazia.uguccioni@irb.unisi.ch
8	Ralf Wagner	Geneart GmbH, Josef-Engert-Str. 9 DE-93049 Regensburg Germany	Tel: +49 941 9427613 Fax: +49 941 9446455 E-mail: ralf.wagner@geneart.com
9	Heribert Stoiber	Innsbruck Medical University Department of Hygiene, Microbiology and Social Medicine Fritz-Pregelstr. 3 AT-6020 Innsbruck Austria	Tel: +43 512 5973405 Fax: +43 512 5972870 E-mail: heribert.stoiber@uibk.ac.at
10	Lazare Kaptue	University of Yaounde I Hematology and Immunology Laboratory P.O. Box 337 Yaounde Cameroon	Tel: +237 793 42 32 Fax: +237 200 90 75 E-mail: prkaptue@hotmail.com