Keywords: Vaccine network; non-human primates; HIV vaccine
This project has led to the formation of a horizontal network of EU participants, all with access to biocontainment facilities suitable for holding macaques infected with pathogens and supporting infrastructure needed to evaluate vaccines effectively. A proof of principle demonstration of an effective coordinated multi-centre vaccine study is being executed, using recombinant vectors to develop a safe and effective AIDS vaccine.
Progress in the development of novel vaccines against many of the infectious diseases that pose a threat to human health, for example HIV, HCV, TB, and Malaria, is restricted by the availability of suitable challenge models, and access to the biocontainment facilities and infrastructure necessary for working with animals infected with human pathogens safely. This problem is most acute when simian models are needed. Within Europe, there are few institutes with adequate facilities, thus restricting opportunities for large multi-variate evaluation of vaccines in a readily comparable manner. No single European country has the required infrastructure. Only a network can therefore generate the critical mass of human and structural resources.
AIDS is a major threat to global human health. According to a WHO estimate, more than 50 million people have been infected globally and over 16 000 new HIV infections occur daily. There is, therefore, a critical need for an effective vaccine against HIV. A major hurdle is the failure to identify correlates of immune protection against AIDS. Thus, there is a need for animal challenge models to evaluate the efficacy as well as the immunogenicity of candidate vaccines. Experimental infection of macaques with simian immunodeficiency virus (SIV) is believed to represent the best model of infection and disease for HIV and AIDS in man. However, the worldwide availability of the facilities and resources for handling infected macaques with SIV under appropriate biocontainment is limiting the size and scope of the preclinical studies using this model.
Recombinant vector vaccines expressing HIV-1 proteins are believed currently to provide the best approach to develop a safe and effective AIDS vaccine. However, experiments using a single recombinant vector often failed to elicit strong serological and cellular immune responses, even after multiple immunisations. The central objective of this proposal is, therefore, to identify which combination of recombinant vaccine vectors are most immunogenic and confer the best protection against viral challenge.
To address this challenge for AIDS vaccine development, AIDS research facilities in Europe with biocontainment facilities suitable for holding SIV-infected macaques are conducting an AIDS vaccine experiment in macaque monkeys, using as vaccine vectors modified vaccinia virus Ankara, Semliki Forest virus and plasmid DNA. These constructs express SIVgag/pol, env, tat, rev, and nef genes or irrelevant genes as control. The immunised animals will be challenged mucosally with a pathogenic SIV. During the immunisation phase and thereafter, blood samples from these animals will be analysed quantitatively for viral-specific antibodies and cellular immune responses, as well as viral replication and concentration after challenge exposure. At the end of the experiment, data analysis conducted by each partner will be shared among all participants and compared. This will allow an in-depth analysis of the group data. The completion of this study will demonstrate an effective working partnership between the participants.
The results will demonstrate which combination of vector immunisation is best suited for the further development of an HIV/AIDS vaccine.
The project already demonstrates that multi-centre controlled vaccine studies can be conducted through a network of European facilities housing non-human primates under appropriate biosafety conditions. The results will contribute to the development of a vaccine applicable for the immune prevention of the HIV infection and AIDS in man.
|Official Address||Other Information|
|2||Martin Cranage||Centre for Applied Microbiology and Research (CAMR) |
UK-SP4 0HG Salisbury
|Tel: +44 1980 612504 |
Fax: +44 1980 611310;
|3||Neil Almond||National Institute for Biological Standards and Control (NIBSC) |
Blanche Lane, South Mimms
UK-EN6 3QG Potters Bar
|Tel: +44 1707 654753 |
Fax: +44 1707 649865
|4||Steven Norley||Robert-Koch-Institut |
|Tel: +49 30 4547 2380 |
Fax: +49 30 4547 2914
|5||Fausto Titti||Istituto Superiore di Sanità (ISS) |
Viale Regina Elena 299
|Tel: +39 06 499 03321 |
Fax : +39 06 493 87184
|6||Jonathan Heeney||Biomedical Primate Research Centre (BPRC) |
Lange Kleiweg 157
NL-2280 GH Rijswijik
|Tel: +31 15 284 2661 |
Fax: +31 15 284 3986
|7||Dominique Dormont||Commissariat á l'Energie Atomique (CEA) |
60-68 Av. de la Division Leclerc
|Tel: +33 1 46 54 81 22 |
Fax: +33 1 46 54 77 26