Keywords: AIDS; HIV; vaccine; protection
With support from two successive EU sponsored consortia (Fifth Framework Programme), we have developed a targeted immunodeficiency virus-like particle vaccine (VLP), which has a heterologous viral surface protein incorporated in the membrane of the particle. This should increase uptake and presentation of VLPs by dendritic cells. A pilot vaccination experiment in the SIV/macaque model provided strong protection against challenge with a pathogenic SIV. Given the urgent need for an HIV vaccine, the potential of this innovative vaccine approach should be evaluated as quickly as possible. Therefore, the aims of the current STREP application of the consortium are 1) to determine the efficacy of the VLPs in a larger number of animals, 2) to understand better the requirements for and the mechanisms of protection, and 3) to further improve the targeted VLPs. The STREP should thus also provide critical information to design evidence-based phase I/II clinical trials with targeted VLPs.
With HIV spreading worldwide, the need for a preventive or therapeutic vaccine is more urgent than ever before. Efficacy studies in humans require large cohorts, and only a single trial using recombinant gp120 surface protein has been performed with no evidence of protection. Therefore, most of our knowledge on efficacy of HIV vaccines comes from animal models, particularly the infection of macaques with simian immunodeficiency viruses (SIV). Work on live attenuated immunodeficiency viruses in non-human primate models has shown that a vaccine can provide protection from progression to AIDS, even in the absence of a sterilising immunity. Thus, vaccine-induced antiviral immune responses can control immunodeficiency virus replication. A number of effector mechanisms, including neutralising antibodies and CD8+ cytotoxic T lymphocytes, are likely to contribute to protection. In addition to the live-attenuated vaccines, which for safety reasons are unlikely to be applicable in humans, a number of vaccine approaches have been studied in the SIV model. Vaccination with recombinant env proteins does not provide sufficient protection against pathogenic SIV either, which is consistent with results from the human phase III trial. Similarly, whole inactivated SIV vaccines and virus-like particles do not provide significant protection, if the challenge virus is grown on monkey cells . A common feature of vaccination with recombinant viral proteins and whole inactivated viruses is injection of exogenous antigens, which predominantly leads to MHC-II restricted cellular immune responses and production of antibodies. Expression of antigens by cells of the vaccinees should lead to presentation of antigens on MHC-I and MHC-II molecules. Therefore, DNA and viral vector vaccines have been extensively studied and depending on the stringency of the challenge system various degrees of protection have been observed.
Instead of using viral vector systems to induce MHC-I and MHC-II-restricted immune responses, a heterologous surface protein was incorporated into immunodeficiency virus-like particles, which should increase uptake and presentation of the exogenous viral antigens on MHC-I and MHC-II molecules. This might explain the initial evidence for protection from disease progression in monkeys immunised with these targeted virus-like particles.
Development of an HIV vaccine.
Confirmation of vaccine efficacy in a larger number of animals.
Better understanding of mechanisms of protection.
HIV vaccine, other vaccines.
Department of Molecular and Medical Virology
Tel: +49 234 3223189
Fax: +49 234 3214352
|Official Address||Other Information|
|2||Paul Racz||Department of Pathology|
Bernhard-Nocht-Institute for Tropical Medicine
|Tel: +49 40 42 818 499 |
Fax: +49 40 42 818 544
|3||Ralph Steinman |
Henry G. Kunkel
|Laboratory of Cellular Physiology and Immunology|
The Rockefeller University
1230 York Avenue
New York, NY 10021-6399
United States of America
|Tel: +1 212 327 8106 |
Fax: +1 212 327 8875
|4||Heribert Stoiber||Department of Hygiene and Social Medicine|
Medical University Innsbruck
|Tel: +43 512 507 3405 |
Fax: +43 512 507 2870
|5||Ralf Ignatius||Department of Medical Microbiology and Infection Immunology |
Charité – University Medicine of Berlin
Campus Benjamin Franklin
|Tel: +49 30 8445 3620 |
Fax: +49 30 8445 3830
|6||Mariagrazia Uguccioni||Institute for Research in Biomedicine|
Via Vincenzo Vela 6
|Tel: +41 91 8200300 |
Fax: +41 91 8200305
|7||Christiane Stahl-Hennig||Deutsches Primatenzentrum (DPZ) GmbH|
|Tel: +49 551 3851154 |
Fax: +49 551 3851184