Summary:

The MuNanoVac STREP project will assess a new vaccine strategy to prevent HIV-1 infection based on a primo-vaccination using a biodegradable synthetic colloidal carrier made of poly-lactic acid (PLA) nanoparticles covered with adsorbed antigens. The aim is to demonstrate that PLA nanoparticles are a perfect transcutaneous or mucosal vaccine vehicle, immunogenic for both arms of immunity and adaptable to many types of antigens as well as easy and simple to produce.

Such nanoparticle-based vaccine carriers will allow targeting dentritic cells or transporting the vaccine through skin or mucosal epithelial barriers. To amplify the mucosal immune response, the project will investigate the potential use of immunomodulator molecules associated with the comparison of two different immunisation routes.

Moreover, the MuNanoVac project will contribute to advancing a promising vaccine approach for HIV that could also prove versatile enough for application to other poverty-related diseases such as tuberculosis. With the proposed vaccine candidate, the project gives Europe a tremendous opportunity to gain leadership in the use of biodegradable nanoparticles for vaccine carriers.

Background:

In order to halt HIV infection spreading, a safe and effective AIDS vaccine for both developing and developed countries is urgently needed. Indeed, HIV is still spreading worldwide with more than 65 million people infected (UNAIDS/WHO 2006) and the number of new infections is rising sharply in Asian countries, Eastern Europe and sub-Saharan Africa. The numerous research efforts carried out in this domain have not yet produced an efficient anti-HIV vaccine.

Many infectious diseases for which no vaccine is available suffer from the absence of a good candidate that allows efficient T and B cell immune responses. In the case of HIV-1 mediated infection, the present postulate is that both arms of the immune response (humoral and cellular) should be stimulated by any potential vaccine candidate. Moreover, recent data on natural primary HIV-1 infection establish that the spreading of the virus in the mucosa is essential for the infection to take place. Hence, every vaccination strategy should be able to elicit a strong mucosal immunity at the potential sites of contamination and prevent spreading of HIV-1 virions.

A future goal for vaccine design is therefore to increase their efficiency by reaching the highest number of antigen-presenting cells (APCs) possible and to achieve the high local concentrations required, inducing a potent immune response. Thus, facilitating vaccine compounds penetration into immunisation sites that are rich in APCs as well as specific migration and activation of APCs that would benefit the efficacy of new vaccines in the induction of protective immune response.

Aim:

Current research in the nanotechnology of biomaterials is aimed at using nanosystems as vaccine carriers able to target dendritic cells (DCs) or allow transport through skin or mucosal epithelial barriers. Results show that not only the colloidal properties but also the polymer composition and macromolecular architecture, are critical in inducing an effective immune response. In this context, MuNanoVac aims at assessing the proof-of-concept of a new vaccine candidate to prevent HIV-1 infection at portal of entry; based on a primovaccination using a biodegradable synthetic colloidal carrier, made of PLA nanoparticles bearing any absorbed HIV-1 antigens on their surface.

Expected results:

The target vaccine candidates will be intensively evaluated and optimised to reach the best potential. The project will cover the necessary steps to achieve a complete proof of concept, including preliminary process development aspects. MuNanoVac will contribute towards:

1. bringing new knowledge and innovative technologies through the HIV vaccine discovery process, and;
2. proposing new vaccine candidates for combating and preventing HIV/AIDS.

Additionally, the project results will be promoted as a basis for developing vaccine candidates for other poverty-related diseases. Indeed, the project aims at establishing a proof-of-concept in order to promote the potential of PLA nanoparticle-based compounds as effective vaccine candidates to support a new HIV vaccine strategy.

Potential applications:

MuNanoVacs aims at an efficient vaccine strategy for the prevention of HIV infection; with a view to treating also other poverty-related diseases. Moreover, the advanced research activities conducted in MuNanoVac will generate novel data on innovative HIV vaccine vehicles with a view to improving the efficacy of the proposed vaccine. This data is crucial for publishing scientific results, contributing to sharply estimating the accuracy and pertinence of such new HIV vaccine candidates; and therefore, for accelerating vaccine development.

Coordinator:

Partners:

Nº	Principal Scientific Participants	Official Address	Other Information
3	Robin SHATTOCK	St George's Hospital Medical School Cranmer Terrace, SW17 0RE London UK	Tel.: +44-20-8725-5855 Fax: +44-20-8725-3487 E-mail: shattock@sgul.ac.uk Website: http://www.sgul.ac.uk
4	Teresa GALLART	Hospital Clínic de Barcelona Villarroel, 170, 08036 Barcelona, Spain	Tel.: +34-932275488 Fax: +34-934518038 E-mail: tgallart@clinic.ub.es
5	Roger LE GRAND	Commissariat à l'Energie Atomique 31-33 rue de la Fédération F-75752 Paris Cedex 15, France	Tel.: +33-1-46 54 87 57 Fax: +33-1-46 56 77 26 E-mail: roger.le-grand@cea.fr Website: http://www.cea.fr
6	Milan RASKA	Palacky University in Olomouc Krizkovského 8 771 47 Olomouc, Czech Republic	Tel.: +42-0585632752 Fax: +42-0585632763 E-mail: raskamil@email.cz Website: http://www.upol.cz
7	Behazine COMBADIERE	Université Pierre et Marie Curie - Paris 6 4 place de Jussieu, 75252 Paris Cedex 06, France	Tel.: +33-1-40779888 Fax: +33-1-40779734 E-mail: combadie@ccr.jussieu.fr Website: http://www.upmc.fr
8	Ulrike BLUME-PEYTAVI	Charité Universitätsmedizin Berlin Schumannstraße 20/21 10117 Berlin, Germany	Tel.: +49-30-450518122 Fax: +49-30-450518952 E-mail: ulrike.blume-peytavi@charite.de Website: http://www.charite.de