Identification and validation of new Schistosoma vaccine candidates using phage-display based systems

• Grant number: 20/01917-9
• Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE
• Start date: August 01, 2020
• End date: July 31, 2024
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Agreement: Agilent
• Principal Investigator: Sergio Verjovski Almeida
• Grantee: Sergio Verjovski Almeida
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Company: Agilent Technologies Brasil Ltda
• City: São Paulo
• Associated researchers: Ana Carolina Tahira ; Eliana Nakano ; James Philip Hewitson ; Leonardo Paiva Farias ; Luciana Cezar de Cerqueira Leite ; Murilo Sena Amaral ; Ricardo de Marco ; Robert Alan Wilson

Abstract

Schistosomiasis is a very debilitating disease, spread across three continents and infecting more than 200 million people. Administration of praziquantel to infected individuals is the basis of current schistosomiasis therapy; however, cure rates of less than 50 % have been recorded and drug tolerance has been already reported, reinforcing the need for new and more effective approaches in reducing morbidity and/or in achieving disease eradication, such the development of a vaccine. Over the last four decades, there have been several attempts to develop a vaccine for schistosomiasis by testing many different vaccine candidates, which were selected on the basis of known location on the parasite and on putative function of the candidate proteins, but the results have been disappointing and there is no vaccine available against the disease to date. Our project aims at identifying new vaccine candidate targets with the use of a novel unbiased screening methodology, namely the use of a phage-display Schistosoma mansoni peptide library constructed by our group with synthetic oligonucleotides that encode the entire set of parasite proteins. This library will be used to screen for peptides recognized by antibodies from a cohort of patients with drug-induced-resistance to S. mansoni infection. Sequencing the phages that are captured in the screening and are significantly enriched across the patient cohort will identify the immunogenic parasite epitopes, which will be considered potential vaccine candidates. We will combine this information with another set of parasite epitopes already identified with the same phage-display library as being captured by antibodies from self-cured rhesus macaques. This set of potential candidates will then be tested for protective efficacy in a mouse model using a phage-display delivery system, which is known to promote a strong immune response and to stabilize the vaccine antigen candidate. With our unbiased high-throughput screening and in vivo testing we expect to identify a set of novel vaccine candidates that achieve WHO goals for a satisfactory protection level against S. mansoni challenge in mice. (AU)