Viral Evolution and Transmission
Viral evolution and transmission
The knowledge of the pathogenic mechanisms of infection and disease guide the development of intervention and prevention strategies and new HIV vaccine candidates. The group focuses mainly on models as mother-to-child transmission of HIV and disease progression in children and adults. In specific our research lines determine the pathways of HIV within the mucosa, which is the site of viral entry, replication and persistence, and the immune responses relevant to interfere with the viral pathways, the ultimate road towards a vaccine or intervention for prevention of infection. Our approach spans from in vitro research at the bench to in vivo application of the research findings in preclinical and clinical studies.
Research activity
Our research lines are:
The mucosa, the main portal of entry of HIV via all routes of transmission, is the site of major immune subversion early after infection. Data indicate that antigen presenting cells are an early target for HIV and may become a source of virus for the surrounding cells affecting in turn innate and adaptive immune responses. Therefore, the group studies with sophisticated imaging technology in vitro and ex vivo: i) the molecular mechanism driving the migration of HIV through the intestinal epithelial barrier; ii) the cellular targets in the mucosa to identify the possible pathways to invade the tissue and disseminate to other organs; and iii) the role of antibodies with different effector functions in changing the pathways of the virus.
The immune response controlling HIV, as the desirable and ultimate immune response induced by an HIV vaccine. Data show that infected children with slow progression of disease and Elite controllers develop neutralizing antibody and ADCC on one side, and on the other have specific patterns of innate immune response. Antibody mediated responses are one of the relevant mechanisms to target and eliminate the virus before it will enter and integrate in the cell. Therefore, the goals are to: i) characterize the specificity of these immune responses to identify relevant targets; ii) develop new approaches to test antibody responses; iii) adopt the immunological analysis in preclinical (in rabbits and macaques) and clinical vaccines studies to identify predictive signatures for the development and prioritization of new HIV-1 vaccine candidates.
Provide in vivo evidence on the relevant immune responses to control the virus. We are coordinating several trials, such as i) CORE007 a therapeutic HIV vaccine trial with a ChadOx prime and MVA boost followed by antiretroviral therapy interruption to study safety and immunogenicity. The final goal is to induce an immunological response that contains the virus and thus, reduces the antiretroviral drug load in patients; ii) PedMAb Phase 1 and Phase 2 clinical trials performed in South Africa, with broadly HIV neutralizing monoclonal antibodies administered to infants to prevent HIV transmission via breast feeding, which is unfortunately a common reality.
