Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 226, Issue 3, Pages 521-527Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiac096
Keywords
Plasmodium falciparum; placental malaria; Aotus monkey; animal model; VAR2CSA
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Funding
- Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health
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Infection of pregnant Aotus monkeys with P. falciparum parasites can replicate the key features of placental malaria in pregnant women, including parasitemia, placental sequestration, and antibody response to VAR2CSA.
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. Plasmodium falciparuminfection of pregnant Aotus nancymaaerecapitulates prominent features of placental malaria in pregnant women: parasitemia with recrudescences; placental sequestration of parasitized erythrocytes that bind chondroitin sulfate A; and serum antibodies that react to VAR2CSA and inhibit parasite binding.
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