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Project

Assessing the antibody responses against arboviruses circulating in Peru – from basic immunology to new diagnostics

Arboviruses represent a serious global health problem. The main vector for the viruses Dengue, Zika, Yellow Fever and Chikungunya is the mosquito Aedes aegypti. Its presence has been reported in at least 18 of the 25 regions in Peru, which results in the cocirculation of these viruses in areas where the mosquito is present. Moreover, fever is the main clinical symptom of these diseases which can be followed by rash, polyarthralgia, neurological syndrome, and haemorrhagic syndrome. This symptomatology coincide with more common infections, making diagnosis based on clinical symptoms alone impossible. The problem with these acute, and often self-limiting, infections is that viral RNA can only be detected during the short viremic phase, and as a result thereof, the vast majority of laboratory diagnoses relies on antibody-detection by serological tests. This is often complicated due to the cross-reactivity of antibodies. To circumvent this problem, having a specific serological diagnostic tests for the detection of different arboviruses simultaneously would provide a major step forward both in primary and reference health care centres. Nowadays, epitope mapping by means of peptide microarray technology represents a highly attractive way to address some important knowledge gaps in arboviral infections. In this study we propose to assess the evolution of antibody-responses to an arbovirus infection in patients sampled at regular time intervals after clinical manifestation (acute sample: 2-7 days after infection vs. post-acute at days: 15, 90 and 180). The RepliTope™ Antigen Collection Pan-Flavivirus microarray from JPT Peptide Technologies (Berlin, Germany) containing whole genome peptide libraries of the related Flaviviridae Dengue virus, Zika virus, Yellow Fever virus and the more distant Togaviridae Chikungunya virus will be used to screen different patient populations. The first population consists of people with a particular primary infection (Dengue, Zika, Yellow Fever or Chikungunya). Their sera collected during clinical manifestation will be evaluated to identify antibodies to immunodominant epitopes and the evolution of antibody specificity will be monitored after clinical manifestation. Second, sera collected from individuals with known previous arbovirus infection(s) or vaccination (e.g. Yellow Fever virus) will be evaluated in order to identify similarities and differences in antibody responses compared to primo infections. The latter will also allow the identification of broadly pan-arbovirus antigens/peptides. Finally, the identification of both species-specific and pan-arbovirus antigens will be used for the development of a more specific diagnostic test and protective vaccines.
Date:1 Apr 2018 →  2 Jun 2022
Keywords:B780-tropical-medicine