EUROVAC: European vaccine effort against HIV/AIDS (cluster proposal, 2-7)

• Research unit: EU RFP
• Project number: 99.0471-2

Key words (English)

HIV; virosomen;
Life Sciences; Medicine; Health; Safety; Scientific Research; Social Aspects

Alternative project number (English)

EU project number: QLK2-CT-1999-01321

Research programs (English)

EU-programme: 5. Frame Research Programme - 1.1.2 Control of infectious diseases

Short description (English)

See abstract

Partners and International Organizations (English)

Coordinator: CNRS, Lyon (F)

Abstract (English)

Immunopotentiating reconstituted influenza virosomes (IRIV) are 150 nm proteoliposomes composed of influenza surface glycoproteins and a mixture of natural and synthetic phospholipids. Due to their size, structure and composition, the IRIVs serve as an antigen carrier system for efficacious vaccination. The exellent characteristics of IRIVs as adjuvants have been demonstrated in several systems. IRIVs as alternative adjuvant system for human use are registered by most European, Asian and American countries in commercial hepatitis A and Influenza vaccines. The virosomal system in combination with Escheriagenâ, a non toxic variant of the Escherichia coli heat-labile toxin, can be used for mucosal immunization. A nasal IRIV influenza vaccine was successfully tested in mice and protects ferrets in influenza virus challenge experiments. The virosomes are taken up by the cell into the phagolysosomal pathway. Acidification of endolysosomal vesicles will result in hemagglutinin mediated fusion and release of the IRIV content into the cytoplasm. Therefore, the virosomal system can also be used to deliver DNA or RNA.gp 120 - virosomesIn our virosomal system, the antigens have to be crosslinked to the carrier. Our currently used cross-linker technique is not suitable for the UG21 gp120 protein, since there is no free SH-group on the HIV antigen. Using other crosslinking approaches, the gp120 could be covalently bound to virosomes. These vaccine formulation were tested for parenteral immnunization or in combination with Escheriagenâ for nasal application. The virosomal formulations induced a systemic immune response (IgG and IgA). A mucosal IgA immune response could be measured in the viginal washes of mice immunized with gp120-virosmes and Escherigenâ.Virosomes as DNA delivery systemDifferent methods were used to encapsulate DNA into virosomes. Unfortunately, the DNA encapsulation was not successful. The packaging efficacy was low and on the other site, in addition after parenteral immunization, the virosomal formulation did not in induce a higher immune response than nacked DNA.We adapted our system for intranasal DNA immunization. Using the mumps plasmid as model, a good systemic and mucosal immune response was induced. We used the same method to encapsulate gagpolnef plasmid into virosomes. These formulations will be tested by our EuroVac partners.

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 99.0471-2