Dengue Antibody Response and Therapeutics in Colombia

The emergence and re-emergence of arboviruses has intensified in recent years, causing major public health problems and costs which affect societies. Latin America has been particularly affected, with a marked increase in arbovirus circulation. Among arboviruses, dengue fever has the most widespread circulation, with a ten-fold increase in cases between 2000 and 2019. Despite advancements in research, no effective treatment for DENV is currently available. Live attenuated vaccines are being licensed, but their availability to communities and effectiveness are still uncertain. The absence of effective treatments for DENV exacerbates the situation in countries heavily burdened by the virus, such as Colombia. In this study, we propose to closely follow two cohorts of patients for dengue infection: cohort 1 that have received Dengvaxia (Dengue Tetravalent Vaccine) and cohort 2 that are naïve to vaccination. This will allow us to: i) isolate and sequence the strains infecting them and therefore have a snapshot of the strains circulating in Colombia during the time of the study;ii) functionally characterise their antibody production response to DENV infection by isolating B cells and characterise, in vitro, the breadth of activity of the produced antibodies against replicative DENV strains; and iii) select antibodies with strong pan-serotype activity to be combined into a therapeutic cocktail. These antibodies have the potential to become therapeutic candidates for the prevention or treatment of dengue fever, a field in which there is a significant need for new therapeutic options. In addition to its significance for the development of therapeutic candidates, this project represents a major step forward in the field of dengue research, both in the present and with regard to future vaccinationj strategies. The human long-term response to tetravalent vaccines and/or infection represents a body of knowledge that will be of use to the entire scientific community, and specifically to regions in which vaccines could be deployed, such as Latin America and the Caribbean islands