EUROVAC: European vaccine effort against HIV/AIDS (cluster proposal, 5-4)

• Unité de recherche: PCRD EU
• Numéro de projet: 99.0471-4
• Titre du projet anglais: EUROVAC: European vaccine effort against HIV/AIDS (cluster proposal, 5-4)

Mots-clé (Anglais)

AIDS/HIV; vaccine; vaccinia; cytotoxic T cells; tetramer;
Life Sciences; Medicine; Health; Safety; Scientific Research; Social Aspects

Autre Numéro de projet (Anglais)

EU project number: QLK2-CT-1999-01321

Programme de recherche (Anglais)

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

Description succincte (Anglais)

See abstract

Partenaires et organisations internationales (Anglais)

Coordinator: CNRS, Lyon (F)

Résumé des résultats (Abstract) (Anglais)

Many viruses and bacteria invade the host through mucosal tissues and cause serious diseases, and thus there is an urgent need for more efficient mucosal vaccines. During the second year of the proposal the safety studies with Modified vaccinia virus Ankara (MVA) were completed. MVA is a candidate vector for vaccination, since it induces specific and protective cellular and humoral immune responses against pathogens in animal models. While targeting effector memory/immune cells to mucosal sites requires mucosal immunization, little is known about the behaviour of MVA in mucosal tissues. In this study we have investigated the fate and biosafety of MVA expressing the reporter luciferase gene, when inoculated by different routes in C57BL/6 mice. Intranasal inoculation targeted the non-replicating virus to the nasal associated lymphoid tissue and the lungs, whereas systemic inoculation led to distribution of MVA in almost all lymphoid organs as well as in lungs and ovaries. In contrast, intravaginal, intrarectal and intragastric inoculations failed to induce efficient infection of lymphoid or non-lymphoid tissues. Upon intranasal inoculation, no inflammatory reactions were detected in the upper and lower airways, and expression of luciferase was not detected in the central nervous system. These results indicate that high doses of recombinant MVA are safe when nasally administered, a vaccination route known to elicit in the female genital tract strong cellular and humoral immune responses against pathogens such as HIV-1 or human papilloma virus.The previously described stable mouse cytotoxic T cell lines specific for pol and gag peptides presented by HLA-A2 were used as tools to standardize the vaccination readouts in peripheral and mucosal vaccination schemes (collaboration with network 8). The results show that both, mucosal and systemic immunization with MVA, are safe and the localization of virus shortly after immunization in peripheral and mucosal sites is described after different routes of immunization. This safety assessment of MVA immunization has now been concluded and the article was just submitted to J. Virol. Intraperitoneal MVA immunization has been show to induce an efficient cytotoxic T cell response detectable without restimulation in vitro. There was a very good correlation between Interferon-? ELISPOT and chromium-release assays. Readouts for cytotoxic T cells are currently developed. For the third year we initiated different prime-boost scenarios that should allow to augment the induction of an efficient cytotoxic T cell response. The project is well within the proposed time.

Références bases de données (Anglais)

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