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AVIP
HIV/AIDS
Framework programme: 6
Call: 1
Project number:
LSHP-CT-2004-503487
EC contribution: € 10,300,000
Duration: 60 months
Type: IP
Starting date: 1 February 2004
Graphic element Aids Vaccine Integrated Project
Keywords: Vaccine; clinical trials; regulatory genes; developing countries; HIV; SHIV

Summary:

Vaccines based on viral structural products (Env/Gag/Pol) alone have failed to prevent infection by HIV/Simian Immunodeficiency Virus (SIV). More recently, vaccines based on viral regulatory gene products (Tat/Rev/Nef) have been shown to contain virus replication and to prevent disease onset. A vaccine combining both regulatory and structural viral antigens (combined vaccine) is likely to be superior to the former since it induces immune responses to both early and late viral products. The mission of the AIDS Vaccine Integrated Project (AVIP) is to develop novel combined vaccines to be tested in phase I preventive and therapeutic trials in Europe, that are suitable for future testing in phase II/III trials in developing countries (DC), and to foster training, technology transfer and community involvement among the EU and DC. To ensure completion of the programme, priority has been given to vaccine combinations containing single antigens for which efficacy has been demonstrated in animal models and phase I studies have been completed or are ongoing.

Background:

New strategies have been recently developed aimed at blocking virus replication and disease onset in the absence of sterilising immunity. Control of virus replication may modify the virus-host interaction, favouring the host immune response, and providing protection to disease progression and virus transmission to healthy individuals. This strategy, useful for both preventive and therapeutic interventions, should include both nonstructural and structural viral products. In fact, the immune responses to the regulatory proteins Tat, Rev and Nef have been shown to play a significant role in controlling disease onset and progression. Further, with regard to Env, modifications have been introduced by partners of this consortium (i.e. deletion of the V2 loop of Env, ?V2-Env) that permit exposure of epitopes that are conserved to circumvent the clade issue. Accordingly, four different vaccine candidates have been selected in AVIP and are:

- Tat ± Env (V2-deleted)
- Nef ± Env (V2-deleted)
- HIV multigene (nef, rev, tat, gag, rt, env)
- Multi-HIV antigens/epitopes [rev, tat, nef, gag (p17, p24) full-length antigens, and over 20 T cell epitopes from Pol, Protease and Env antigens]

The efficacy of the different antigens present in the AVIP vaccine candidates has been shown in animal models and these antigens have been, or are being, tested on humans (see Table 1). Comparative analysis in both preclinical studies and phase I therapeutic and preventive trials of these vaccines will be key for the selection of vaccine candidates for phase II/III trials in DC. To this end, clinical sites have already been set up in Estonia, Finland, Germany, Italy, Sweden and the United Kingdom. Partners involved in the clinical development have wide experience with regulatory issues, good manufacturing practice (GMP) production, study design and site preparation, ethical issues and Community Advisory Board (CAB) involvement. In addition, the support of the already established Programe European Vaccine against Aids (EVA) Centralised Facility for AIDS Reagents (National Institute for Biological Standards and Control - NIBSC, UK) with repository and distribution function is of key value to this project. This will constitute an optimal basis for the standardisation of techniques and procedures, and for supporting all AVIP research, technological development and demonstration activities.

Aim:

The general aim of AVIP is to generate novel HIV-1 vaccine candidates to be tested in phase I preventive and therapeutic trials in Europe within a five-year programme (see Table II for vaccine development pipeline). To achieve this goal, four novel vaccines have been selected from a larger pool based on two criteria: the combination of HIV regulatory (Tat and/or Rev, and/or Nef) with structural (Env and/or Gag/Pol) genes/products, and the advanced stage of development of the single components, including efficacy studies in both monkeys and new murine models, GMP process development and phase I studies. Training, education and technology transfer activities are also within the general scope of the programme and are viewed as preparatory to advanced clinical trials with selected AVIP vaccine candidates that will eventually be performed in DC.

Therefore, AVIP major objectives are:

1.To conduct parallel preventive and therapeutic phase I trials in Europe with four novel combined vaccines. The candidates will be first tested in preclinical models to optimise the formulations and the vaccination protocols.
2.To perform feasibility studies and technology transfer in DC for future phase II/III trials.
3.To carry out training in EU countries and DC. To this end, the AVIP International School has been established.
4.To ensure community involvement both in EU countries and DC to guarantee the correct ethical information of the volunteers, counselling, quality of life evaluation and risk assessment.The AVIP project is managed through a steering committee (SC), which is the governing body of the AVIP. The SC is supported by the advisory board (AB) and the monitoring committee (MC), which oversee the scientific, technological, innovative, regulatory, clinical, and training-related activities of the project, with particular regard to ethical and social issues, including community involvement and gender issues.

Potential impact:

  1. The combination of regulatory and structural genes to generate vaccines against HIV/AIDS will potentially ensure an immune response to both early and late gene products, thereby stimulating a broad and potentially protective immune response. The advanced stage of development of the combined vaccine candidates will ensure completion of four therapeutic and four prophylactic phase I clinical trials within the programme in the most cost-effective way.
  2. Cooperation with DC is one of the main activities of AVIP. This collaboration constitutes the basis for building up the capacity in DC sites. The training and standardisation of techniques and procedures, in both the clinical sites and core laboratories for performing phase I clinical trials in EU, will ensure the reproducibility of all results among the various sites, and the maintenance of the highest level of internal and external quality control. Of critical importance will be the establishment or expansion of CAB in the EU and with DC to ensure the ethical recruitment of volunteers, volunteers’ information, quality of life and risk assessment, and communication issues.
  3. Training in a broader sense is also being pursued in all AVIP activities, both in the EU and in DC, at both the levels of development and demonstration activities. The AVIP International School, which has been created by joining existing centres in the EU and South Africa, will be the main instrument for the training activity. As many of the assays and other aspects of the phase I trials will be used in future phase II and III trials in South Africa, the participation of South African researchers will promote continuity in the development of the vaccines.
  4. The support of the already established Programme EVA Centralised Facility for AIDS Reagents, which has repository and reagent distribution functions, gives added value to this project. It alsoconstitutes an optimal basis for the harmonisation and standardisation of techniques and procedures, and for supporting all RTD and demonstration activities.
  5. The AVIP consortium is exploiting synergies with national and international ongoing programmes, including the following that are already existing: (i) national programme in the participating countries, such as the Italian Concerted Action on HIV/AIDS Vaccine development (ICAV) and the Swedish International Development Cooperation Agency (SAREC/SIDA), and (ii) bilateral programmes with DC (Italy-South Africa, Italy-Uganda, Italy-Swaziland, Sweden-Tanzania, UK-Uganda) and European programmes, such as the HIV Incidence Study (HIVIS) and theVery Innovative AIDS Vaccine (VIAV). In this respect, the AVIP consortium is also establishing interactions with international organisations, so that co-operation with other EU and international networks and agencies is foreseen.
  6. Scientific publications and communications at national and international meetings will constitute an additional forum for AVIP dissemination plans in the scientific and industrial community. Promotion of public awareness concerning the goals, activities and results of the AVIP consortium will be ensured by an internet web site (http://www.avip-eu.org), which is being developed for disseminating AVIP results and for internal consortium management.

The results of the AVIP programmemay lead to significant improvement of living conditions in both developing and developed countries. By increasing human life expectancy and health of the youth, the major workforce of the countries affected by the HIV epidemic will be preserved, thereby reducing the tremendous social and economic loss due to AIDS.

For further information, see http://www.avip-eu.org

Coordinator:

Barbara Ensoli
AIDS Division, Istituto Superiore di Sanità
Viale Regina Elena 299
00161 Rome
Italy
Tel: +39 06 4990 3209
Fax: +39 06 4990 3002
E-mail: ensoli@iss.it

Partners:

Principal
Scientific
Participants
Official Address Other Information
2Britta WahrenMicrobiology and Tumorbiology Centre
Karolinska Institute
SE-171 82 Stockholm, Sweden
Tel: +46 8 457 2630
Fax: +46 8 33 72 72
E-mail: britta.wahren@smi.ki.se
3Roger Le GrandSNV/DRM/SDV/CEA Laboratoire
d’Immuno-Pathologie Experimentale (LIPE)
18 Route du Panorama
FR-92265 Fontenay-Aux-Roses, France
Tel: +33 1 46 54 73 74
Fax: +33 1 46 54 77 26
E-mail: legrand@dsvidf.cea.fr
4Antonella CaputoDepartment of Experimental and Diagnostic Medicine – Section of Microbiology
Via Luigi Borsari 46
IT- 44100 Ferrara, Italy
Tel: +39 0532 2291330
Fax: +39 0532 2247618
E-mail: cpa@unife.it
5Carlos Alberto GuzmanMicrobial Pathogenicity and Vaccine Research, Vaccine Research Group
GBF – Gesellschaft für Biotechnologische Forschung mbH
Mascheroder Weg 1
DE-38124 Braunschweig, Germany
Tel: +49 531 6181-558
Fax: +49 531 6181-411
E-mail: cag@gbf.de
6Mauro MagnaniInstitute of Biological Chemistry ‘G. Fornaini’, University of Urbino
Via Saffi, 2
IT-61029 Urbino, Italy
Tel: +39 0722 305211
Fax: +39 0722 320188
E-mail: magnani@uniurb.it
7Kai KrohnScience and Technology
HIV Vaccine, FIT Biotech Oyj
Biokatu 10
FI-33520 Tampere, Finland
Tel: +358 4 08331366
Fax: +358 3 31387050
E-mail: kai.krohn@fitbiotech.com
8Volker ErfleGSF Forschungszentrum für Umwelt und Gesundheit GmbH Institut für Molekulare Virologie
Ingolstädter Landstrasse 1
DE-85764 Neuherberg, Germany
Tel: +49 89 3187 2213
Fax: +49 89 3187 3329
E-mail: erfle@gsf.de
9Rino RappuoliResearch Centre –
Chiron Vaccines, Chiron S.r.l.
Via Fiorentina 1
IT-53100 Florence, Italy
Tel: +39 0577 243414
Fax: +39 0577 243564
10Frances GotchDepartment of Immunology, Imperial College, Chelsea and Westminster Hospital
369 Fulham Road
UK-SW10 9NH London, United Kingdom
Tel: +44 208 746 8257
Fax: +44 208 746 5997
E-mail: f.gotch@imperial.ac.uk
11Eftyhia VardasPerinatal HIV Research Unit of the Wits Health Consortium
9th Floor, Nurses Residence
Chris Hani Baragwanath Hospital
Old Potchefstroom Road
Bertsham, 2013 - Diepkloof
Sowetho, South Africa
Tel: +27 11 989 9756
Fax: +27 11 938 3973
E-mail: vardase@mweb.co.za
12Estrelita Janse van RensburgMedical Virology/Health Sciences
Francie van Zijl Drive - P.O. Box 19063, 7505
Tygerberg, South Africa
Tel: +27 21 938 9353
Fax: +27 21 938 9361
E-mail: ejvr1@sun.ac.za
13Mario ClericiDipartimento di Scienze Precliniche (DISP) LITA Vitalba/Facoltà di Medicina e Chirurgia -
Cattedra di Immunologia e Immunopatologia
Via GB Grassi 74
IT-20157 Milan, Italy
Tel: +39 02 5031 9679
Fax: +39 02 5031 9677
E-mail: mario.clerici@unimi.it
14Guido PoliDIBIT/AIDS Immunopatogenesis Unit
Via Olgettina 58
IT- 20132 Milan, Italy
Tel: +39 02 2643 4909
Fax: +39 02 2643 4905
E-mail: poli.guido@hsr.it
15Harvey HolmesNational Biological Standards Board (NIBSC) Retrovirology Division
Blanche Lane, South Mimms
UK-EN6 3QG Potters Bar, United Kingdom
Tel: +44 1707 651000
Fax: +44 1707 649865
E-mail: hholmes@nibsc.ac.uk

 
 
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