Project description:Non-human primates belonging to the Aotus genus have been shown to be excellent experimental models for evaluating drugs and vaccine candidates against malaria and other human diseases. The immune system of this animal model must be characterised to assess whether the results obtained here can be extrapolated to humans. Class I and II major histocompatibility complex (MHC) proteins are amongst the most important molecules involved in response to pathogens; in spite of this, the techniques available for genotyping these molecules are usually expensive and/or time-consuming. Previous studies have reported MHC-DRB class II gene typing by microsatellite in Old World primates and humans, showing that such technique provides a fast, reliable and effective alternative to the commonly used ones. Based on this information, a microsatellite present in MHC-DRB intron 2 and its evolutionary patterns were identified in two Aotus species (A. vociferans and A. nancymaae), as well as its potential for genotyping class II MHC-DRB in these primates.
Project description:Plasmodium falciparum-infected erythrocytes that display the variant surface antigen VAR2CSA bind chondroitin sulfate A (CSA) to sequester in placental intervillous spaces, causing severe sequelae for mother and offspring. Here, we establish a placental malaria (PM) monkey model. Pregnant Aotus infected with CSA-binding P. falciparum CS2 parasites during the third trimester developed pronounced sequestration of late-stage parasites in placental intervillous spaces that express VAR2CSA and bind specifically to CSA. Similar to immune multigravid women, a monkey infected with P. falciparum CS2 parasites over successive pregnancies acquired antibodies against VAR2CSA, with potent functional activity that was boosted upon subsequent pregnancy infections. Aotus also developed functional antibodies after multiple acute PM episodes and subsequent VAR2CSA immunization. In summary, P. falciparum infections in pregnant Aotus monkeys recapitulate all the prominent features of human PM infection and immunity, and this model can be useful for basic mechanistic studies and preclinical studies to qualify candidate PM vaccines. Clinical Trials Registration: NCT02471378.
