Rhesus macaques self-curing from a schistosome infection can display complete immunity to challenge

Author(s):Show less -

Amaral, Murilo Sena ^[1] ; Santos, Daisy Woellner ^{[2, 1]} ; Pereira, Adriana S. A. ^{[2, 1]} ; Tahira, Ana Carolina ^[1] ; Malvezzi, Joao V. M. ^[1] ; Miyasato, Patricia Aoki ^[1] ; Freitas, Rafaela de Paula ^[1] ; Kalil, Jorge ^[3] ; Fat, Elisa M. Tjon Kon ^[4] ; de Dood, Claudia J. ^[4] ; Corstjens, Paul L. A. M. ^[4] ; van Dam, Govert J. ^[5] ; Nakano, Eliana ^[1] ; Castro, Simone de Oliveira ^[6] ; de Moura Mattaraia, Vania Gomes ^[6] ; Augusto, Ronaldo de Carvalho ^{[7, 8]} ; Grunau, Christoph ^[8] ; Wilson, R. Alan ^[9] ; Verjovski-Almeida, Sergio ^{[2, 1]}

Affiliation

^[1] Inst Butantan, Lab Parasitol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, Heart Inst, Sao Paulo - Brazil

^[4] Leiden Univ, Dept Cell & Chem Biol, Med Ctr, Leiden - Netherlands

^[5] Leiden Univ, Dept Parasitol, Med Ctr, Leiden - Netherlands

^[6] Inst Butantan, Bioterio Cent, Sao Paulo - Brazil

^[7] Univ Lyon, Lab Biol & Modelisat Cellule, Univ Claude Bernard Lyon 1, CNRS, UMR 5239, INSERM, U1210 Lyon, LBMC, ENS Lyon, Lyon - France

^[8] Univ Perpignan, IHPE, Univ Montpellier, CNRS, IFREMER, Via Domitia, Perpignan - France

^[9] Univ York, York Biomed Res Inst, Dept Biol, York, N Yorkshire - England

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 12, n. 1 OCT 26 2021.
• Web of Science Citations: 0

Abstract

To date there is only one single drug with modest efficacy and no vaccine available to protect from schistosomiasis. Here, Amaral et al. characterize the self-cure process of rhesus macaques following primary infection and secondary challenge with Schistosoma mansoni to inform future vaccine development studies. The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict >200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an established infection with Schistosoma mansoni is cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrates that protection is strong in all animals and complete in some. Antibody profiles suggest that antigens mediating protection are the released products of developing schistosomula. In culture they are killed by addition of rhesus plasma, collected from week 8 post-infection onwards, and even more efficiently with post-challenge plasma. Furthermore, cultured schistosomula lose chromatin activating marks at the transcription start site of genes related to worm development and show decreased expression of genes related to lysosomes and lytic vacuoles involved with autophagy. Overall, our results indicate that enhanced antibody responses against the challenge migrating larvae mediate the naturally acquired protective immunity and will inform the route to an effective vaccine. (AU)

• FAPESP's process: 16/10046-6 - Effect of GSK343, an inhibitor of the histone methyltransferase EZH2, on the parasite Schistosoma mansoni
• Grantee: Adriana Silva Andrade Pereira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/06366-2 - Assessing the mechanisms of self-cure in rhesus macaques infected with Schistosoma mansoni as a new basis for a vaccine
• Grantee: Sergio Verjovski Almeida
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/09404-3 - Identification through phage display with cDNAs synthetic library of antigenic epitopes of Schistosoma mansoni targeted by the immune response of Rhesus monkeys (Macaca mulatta) infected by the parasite and self-cured
• Grantee: Daisy Woellner Santos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/15049-9 - EPICURE: assessing the epigenetic changes in Schistosoma mansoni developmental trajectory after in vitro treatment with serum from schistosomiasis self-cured rhesus macaques
• Grantee: Sergio Verjovski Almeida
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/18117-5 - Phage display identification of vaccine candidates for schistosomiasis based on self-healing of rhesus monkeys (Macaca mulatta)
• Grantee: João Vicente de Morais Malvezzi
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/23693-5 - Mechanisms of action of long non-coding RNAs involved with gene activation programs in eukaryotes
• Grantee: Sergio Verjovski Almeida
• Support Opportunities: Research Projects - Thematic Grants