Projects

HIV-infected patients present a higher prevalence of morbidities and immunosenescence (aging of the immune system). In aged organisms, the accumulation of cells with unrepaired DNA lesions contributes to genome instability, rendering them more susceptible to enter senescence. Although genomic instability is one of the hallmarks of aging and senescence, the relationship between immunosenescence and genomic instability remains to be described/has not been assessed. The overall objective of the project is to determine the prevalence of immunosenescence, cellular aging and senescence markers (shortening of telomeres, DNA damage, 53BP1 recruitment, cell proliferation capacity and expression of senescence markers) in HIV-infected and uninfected adults (40-45 years) and elderly (60-70 years).

We aim to:

1. Establish the relation between these two mechanisms (immunosenescence and cellular aging/senescence 
2. Determine if HIV induces them earlier and in a more accelerated way 
3. Characterize target biomarkers that would allow their surveillance in these patients.

• Funding entity: Ministry of Science, Innovation and Universitites - Carlos III Health Institute (ISCIII)

The membrane proximal external region (MPER) of the HIV envelope glycoprotein is a target for generating neutralizing antibodies. We have identified a miniprotein derived from gp41 which, in the form of proteoliposomes, generates strong humoral responses in murine models. Our results, however, demonstrate the presence of both neutralizing and non-neutralizing responses to the MPER. Therefore, in this project we propose:

1. To define the structural determinants associated with neutralizing and non-neutralizing activity.

2. To define the role of lipids in the structure of the protein.

3. To integrate the data in a new improved immunogen.

The methodology includes epitope mapping, antibody isolation and mutagenesis and molecular modelling and murine modelling of immunization.