Schistosoma mansoni vaccine candidates identified by unbiased phage display screening in self-cured rhesus macaques

Author(s):Show less -

Woellner-Santos, Daisy ; Tahira, Ana C. ; Malvezzi, Joao V. M. ; Mesel, Vinicius ; Morales-Vicente, David A. ; Trentini, Monalisa M. ; Marques-Neto, Lazaro M. ; Matos, Isaac A. ; Kanno, Alex I. ; Pereira, Adriana S. A. ; Teixeira, Andre A. R. ; Giordano, Ricardo J. ; Leite, Luciana C. C. ; Pereira, Carlos A. B. ; DeMarco, Ricardo ; Amaral, Murilo S. ; Verjovski-Almeida, Sergio

• Document type: Journal article
• Source: NPJ VACCINES; v. 9, n. 1, p. 19-pg., 2024-01-04.

Abstract

Schistosomiasis, a challenging neglected tropical disease, affects millions of people worldwide. Developing a prophylactic vaccine against Schistosoma mansoni has been hindered by the parasite's biological complexity. In this study, we utilized the innovative phage-display immunoprecipitation followed by a sequencing approach (PhIP-Seq) to screen the immune response of 10 infected rhesus macaques during self-cure and challenge-resistant phases, identifying vaccine candidates. Our high-throughput S. mansoni synthetic DNA phage-display library encoded 99.6% of 119,747 58-mer peptides, providing comprehensive coverage of the parasite's proteome. Library screening with rhesus macaques' antibodies, from the early phase of establishment of parasite infection, identified significantly enriched epitopes of parasite extracellular proteins known to be expressed in the digestive tract, shifting towards intracellular proteins during the late phase of parasite clearance. Immunization of mice with a selected pool of PhIP-Seq-enriched phage-displayed peptides from MEG proteins, cathepsins B, and asparaginyl endopeptidase significantly reduced worm burden in a vaccination assay. These findings enhance our understanding of parasite-host immune responses and provide promising prospects for developing an effective schistosomiasis vaccine. (AU)

• 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: 20/01917-9 - Identification and validation of new Schistosoma vaccine candidates using phage-display based systems
• Grantee: Sergio Verjovski Almeida
• Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE
• FAPESP's process: 21/10124-5 - Designing Sars-Cov-2 Mono-ADP-ribosyl hydrolase Enzyme Inhibitors: A New Class of Antiviral Agents?
• Grantee: Isaac de Araujo Matos
• 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: 19/02305-0 - Investigation of immune response mechanisms effective of a BCG Vaccine Recombinant against Tuberculosis by Systems Biology
• Grantee: Lázaro Moreira Marques Neto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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: 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)