09/01/2012

IrsiCaixa describes new natural HIV-controlling mechanisms that the AIDS vaccine will have to induce

The IrsiCaixa Aids Research Institute, jointly promoted by the “la Caixa” Foundation and the Health Department of the Generalitat de Catalonia, has described some very effective immune response characteristics which enable HIV-positive patients to naturally control infection with very low virus levels.
IrsiCaixa researchers highlight the fact that future vaccine candidates will have to stimulate the immune system by following the same characteristics described in the immune system of these people and also describe which HIV fragments are most active and therefore most effective to be incorporated into the vaccine.
The study provides guidelines for researchers worldwide who are designing candidates for an anti-AIDS vaccine and has been developed within the framework of the programme for the development of the HIVACAT AIDS vaccine, promoted by an unprecedented public-private consortium in our country.

Three studies recently published in the Journal of Virology, in the Journal of Translational Medicine and in PLOS One, by the IrsiCaixa AIDS Research Institute, jointly promoted by the “la Caixa” Foundation program and the Health Department of the Generalitat de Catalonia, describe new natural HIV-controlling mechanisms found in people who are able to maintain undetectable or very low virus levels in the blood without medication. Gaining deeper insight into the characteristics of this very effective immune response enables scientists to understand how to better develop a vaccine capable of imitating these characteristics, overcoming the biggest obstacle to the development of an HIV vaccine: that it is able to protect against the large variability of virus that exists not only in the world, but within each infected person.

In order to decipher the mechanisms of the immune system, the scientists have analysed blood samples from nearly 1000 HIV-positive patients from 3 different continents (Africa, South America and Europe). Scientists have studied the immune response against HIV, specifically, the response mediated by white blood cells called T lymphocytes, the role of which is believed to be key in the action of a vaccine.

The study confirms that the response that is found in patients who control HIV naturally targets virus fragments that are highly preserved, meaning they undergo very few mutations, and identifies the most active virus fragments when stimulating the immune system of these individuals. Therefore, the fragments described that induce a good immune response, such as the ones presented in the study, and which are most active, could become a part of the AIDS vaccine and prove effective against the immense variety of HIV strains.

The new immune response characteristics that have been described, which are found in patients who control HIV at very low levels and which will have to be imitated in a vaccine, are mainly two. On the one hand, this T lymphocyte-mediated response is effective even in cases where there is mutation in these preserved regions, which scientists describe as the response having an elevated cross reactivity capacity. On the other hand, the active response, even when there is a very low concentration of the virus fragment, which is essential for a vaccine to be effective but not toxic. This low concentration of fragments will have to be sufficient to activate the response, which scientists call “high functional avidity”. It seems that if few fragments are needed, the immune system is able to detect infected cells shortly after the virus has penetrated the body, and it is therefore capable of stopping the infection from growing.

According to the coordinator of the research project, ICREA researcher from IrsiCaixa Christian Brander, who is also the scientific coordinator of the programme for the development of the HIVACAT vaccine, the published studies “have helped researchers to design the vaccine candidates which the Institute is currently developing, and which are composed of the HIV fragments identified in the studies. IrsiCaixa has been able to identify the best regions of the virus to include and test whether they stimulate a good immune response such as the one described in the study, in order for the vaccine to be able to prevent the spreading of infection once the virus penetrates into the body”.