The study, published in NPJ Vaccines, shows that the particles may be useful as a therapeutic or preventive vaccine against HIV
HIV is able to escape our defences. For this reason, many of the therapeutic strategies against HIV seek to reactivate the immune system's response so that it can carry out its function and eliminate the virus. Now, the IrsiCaixa AIDS Research Institute has produced virus-like particles (VLPs) that contain parts of HIV but are not infectious and, in preclinical studies, stimulate the immune system. These particles trigger the production of large quantities of effective antibodies. The results obtained are proof of concept that, although optimisation of the immune response generated by the particles is necessary, the vaccine platform designed at IrsiCaixa is functional and has potential as a preventive and/or therapeutic strategy against HIV and other infectious diseases, but also as a therapeutic strategy against cancer.
Antigens are particles detected by our defences as molecules foreign to our own body. When the immune system encounters an antigen, it understands that it is facing a threat and activates a protective response to eliminate it. "We want to identify and use these antigens to teach the immune system to initiate all the processes necessary to eliminate HIV. However, this virus is very complex and, to deal with it, you need to expose the immune system to a large number of antigens to get an effect. This is a great challenge because producing large proteins at such a high density is very complicated," explains Julià Blanco, principal investigator at IrsiCaixa and IGTP. To do this, the research team has designed virus-like particles, which are characterised by not being infectious and not being able to multiply, containing more than 2,000 proteins similar to HIV gp41, a protein density more than 10 times higher than that contained in the VLPs generated so far.
VLPs induce a strong antibody response
Through preclinical studies, the research team has shown that vaccination with VLPs generates a strong immune response. This response is centred on the production of antibodies to the HIV proteins present on the VLPs. "In preclinical studies, the levels of antibodies produced after vaccination are 100 times higher than those of other vaccines tested," says Ferran Tarrés, first author of the article and researcher on the project during his thesis at IrsiCaixa. Although these antibodies have not been shown to neutralise HIV, i.e. they do not block infection, they could develop other very useful functions, such as the destruction of infected cells. "To demonstrate this, we have tested the effectiveness of VLPs against cancer cells specifically modified to produce the gp41 protein, the HIV antigen that VLPs present and, therefore, for which the immune system will generate antibodies. In this way we have been able to see that the vaccine is effective because, in this context, it produces antibodies capable of binding to cancer cells and activating an immune response that attacks them, reducing tumour progression," explains Carmen Aguilar, senior researcher at IrsiCaixa. "All these data show that, although it is necessary to optimise the design of the antigen used to achieve a neutralising response in the case of HIV, the vaccine platform is effective and serves as a structure for further work on therapeutic vaccines," says Blanco.
A platform of vaccines available against HIV and other diseases
VLPs are a strategy that allows us to generate vaccines against any threat to the body that is recognisable by the immune system. "We can create VLPs 'a la carte', that is, we have generated a vaccine platform that allows us to design particles that attack the threat we choose, from HIV to cancer cells," says Jorge Carrillo, principal investigator at IrsiCaixa. However, the challenge of this strategy is to find the ideal molecule to incorporate into the particles, as it must be capable of activating the immune system and eliciting a response powerful enough to eliminate the foreign agent. IrsiCaixa is working to identify the most optimal antigens against HIV and some cancers, such as pancreatic cancer. "The results of this study are very useful to know what the molecule we should include in VLPs against HIV should be like, and it guides us to continue advancing in the right direction," concludes Blanco.