RESISTOME-HIV (Genética de la resistencia a la infección por VIH y respuesta a vacunas)

The identification of immunological, genetic or environmental factors related to protection after
vaccination would be a great advance in the development of vaccines against HIV-1. Hypothesis: Genetic resistance to HIV-1 and vaccine efficacy is determined by variations in the expression, structure, and function of innate immunity genes. Parallel genotyping of cohorts at risk of HIV infection through sexual or parenteral routes, as well as the genetic study of placebo/vaccine-treated volunteers from the Vax004 clinical trial could make it possible to distinguish between genetics of vaccine response and susceptibility genetics.
In a previous project financed by MINECO, we have carried out a complete genome study of a set of
Spanish sexually transmitted (Córdoba, Jaén, Madrid) and international (Milan-Italy, Vaxgen-San Francisco-USA) cohorts that have allowed us to discover new biomarkers associated with the risk of HIV-1 infection. We genotyped these samples (sexual cohorts and Vaxgen) with the Illumina Global Screening Array platform (650,000 direct markers and 8 million imputed markers). Having found signs of association with risk of HIV infection in the following loci among others:
• Chromosome 4: It is associated by GWAS with the levels of total lymphocytes in peripheral blood. In
addition to other phenotypes related to the immune response such as asthma or inflammatory bowel
disease.
• Chromosome 7: Region previously associated in other GWAS with leukocyte and eosinophil levels in
peripheral blood, but imperfectly characterized.
• Chromosome 13: gene involved in the functional activation of genes induced by interferon, which
generate a post-translational modification necessary for its antiviral activity (inhibition of fusion pore
formation between viral and cellular membranes).
Regarding the incidence of post-vaccination infection, the genomic signals found are very interesting, with
a gene previously associated with the response to the smallpox vaccine, genes involved in Gap-type
junctions, and most surprisingly, several genes involved. in bipolar disorder and schizophrenia.The
identification of genes associated with protection against HIV infection is essential to understand the
molecular mechanisms involved in the infection process, the innate and adaptive immune response against the virus, identify potential drug targets, and improve the efficacy of vaccines under development and increase the patient’s response to therapy.
The data requested from CEGEN on healthy donors will allow us to carry out gene association studies with sexually infected HIV-positive patients (Cohorts from Málaga and Lleida) and replicate the data obtained in the previous study in independent populations.