A refined genome phage display methodology delineates the human antibody response in patients with Chagas disease

Author(s):Show less -

Reis Teixeira, Andre Azevedo ^{[1, 2]} ; Carnero, Luis Rodriguez ^[1] ; Kuramoto, Andreia ^[3] ; Tang, Fenny Hui Fen ^{[1, 4]} ; Gomes, Carlos Hernique ^[1] ; Pereira, Natalia Bueno ^[3] ; de Oliveira, Lea Campos ^[5] ; Garrini, Regina ^[5] ; Monteiro, Jhonatas Sirino ^[1] ; Setubal, Joao Carlos ^[1] ; Sabino, Ester Cerdeira ^[5] ; Pasqualini, Renata ^{[6, 4]} ; Colli, Walter ^[1] ; Arap, Wadih ^{[6, 7]} ; Manso Alves, Maria Julia ^[1] ; Cunha-Neto, Edecio ^{[8, 3, 9]} ; Giordano, Ricardo Jose ^{[1, 8]}

Affiliation

^[1] Univ Sao Paulo, Inst Chem, Dept Biochem, BR-05508000 Sao Paulo, SP - Brazil

^[2] Specifica Inc, Los Alamos, NM - USA

^[3] Univ Sao Paulo, Heart Inst InCor, Sch Med, BR-05403000 Sao Paulo, SP - Brazil

^[4] Rutgers New Jersey Med Sch, Dept Radiat Oncol, Div Canc Biol, Newark, NJ 07103 - USA

^[5] Univ Sao Paulo, Inst Trop Med, Sch Med, BR-05403000 Sao Paulo, SP - Brazil

^[6] Rutgers Canc Inst New Jersey, Newark, NJ 07103 - USA

^[7] Rutgers New Jersey Med Sch, Dept Med, Div Hematol Oncol, Newark, NJ 07103 - USA

^[8] INCT, Inst Invest Immunol 3, Sao Paulo, SP - Brazil

^[9] Univ Sao Paulo, Div Clin Immunol & Allergy, Sch Med, BR-01246903 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: ISCIENCE; v. 24, n. 6 JUN 25 2021.
• Web of Science Citations: 0

Abstract

Large-scale mapping of antigens and epitopes is pivotal for developing immunotherapies but challenging, especially for eukaryotic pathogens, owing to their large genomes. Here, we developed an integrated platform for genome phage display (gPhage) to show that unbiased libraries of the eukaryotic parasite Trypanosoma cruzi enable the identification of thousands of antigens recognized by serum samples from patients with Chagas disease. Because most of these antigens are hypothetical proteins, gPhage provides evidence of their expression during infection. We built and validated a comprehensive map of Chagas disease antibody response to show howlinear and putative conformation epitopes, many rich in repetitive elements, allow the parasite to evade a buildup of neutralizing antibodies directed against protein domains that mediate infection pathogenesis. Thus, the gPhage platform is a reproducible and effective tool for rapid simultaneous identification of epitopes and antigens, not only in Chagas disease but perhaps also in globally emerging/reemerging acute pathogens. (AU)

• FAPESP's process: 14/21177-9 - Identification of molecular markers for the development of novel therapeutic agents with angiogenic properties
• Grantee: Ricardo Jose Giordano
• Support Opportunities: Regular Research Grants