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Content archived on 2024-06-25

Explaining and Improving Efficacy of targeted Immunodeficiency Virus-like Particles against AIDS

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HIV vaccine needed ASAP

Until now, most work on HIV vaccines has used animal models, as various problems present in conducting studies on humans. However, with HIV infecting some 40 million people worldwide, development of a preventive or therapeutic vaccine is a top priority.

The 'Explaining and improving efficacy of targeted immunodeficiency virus-like particles against AIDS' (Tip-vac) project has developed a targeted immunodeficiency virus-like particle (VLP) vaccine with a G-protein incorporated in the membrane of the particle. The project aimed to determine the efficacy of the VLPs in a larger number of animals, generate more information on the requirements for protection and its mechanisms, and continue work to improve the targeted VLPs. G-proteins transmit chemical signals outside the cell and bring about changes inside the cell. In this study, researchers used the vesicular stomatitis virus G-protein, which is a model transmembrane glycoprotein widely used to study the pathway along which cell contents are secreted. A pilot vaccination experiment on macaque monkeys infected with simian immunodeficiency viruses (SIVs) showed strong protection could be achieved with a pathogenic SIV. Work on other immunodeficiency viruses using a pathogen whose virulence has been weakened but not 'inactivated' (live-attenuated) in non-human primate models has revealed that a vaccine can protect against the progression to AIDS. This means that using a vaccine to bring on antiviral immune responses can inhibit replication of the immunodeficiency virus. However, for reasons of safety, it isn't likely that live-attenuated vaccines will be applied to humans. With other studies showing no protection, extensive work was performed on DNA and viral vector vaccines to induce MHC-I and MHC-II-restricted immune responses. Tip-vac results showed various degrees of protection. MHC (major histocompatibility complex) molecules are found on specialised cell types such as dendritic cells, the immune cells that process antigen material and present it to other immune system cells. By choosing to incorporate heterologous fusion proteins (created through the joining of two or more different genes) into immunodeficiency VLPs, Tip-vac project partners believe their approach can increase the uptake and presentation of VLPs by dendritic cells. Work in this area needs to quickly evaluate findings and propose evidence-based phase I/II clinical trials with targeted VLPs.

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