Elucidating the 3D structure of a surface membrane antigen from Trypanosoma cruzi as a serodiagnostic biomarker of Chagas disease

DOI: 10.3390/vaccines10010071

Authors: Flavio Di Pisa (Università degli Studi di Milano) , Stefano De Benedetti (Università degli Studi di Milano) , Enrico Mario Alessandro Fassi (Consiglio Nazionale delle Ricerche, Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” (SCITEC); Università degli Studi di Milano) , Mauro Bombaci (IRCCS Ospedale Maggiore Policlinico) , Renata Grifantini (0000-0002-9887-4165) , Angelo Musicò (Consiglio Nazionale delle Ricerche, Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” (SCITEC)) , Roberto Frigerio (Consiglio Nazionale delle Ricerche, Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” (SCITEC)) , Angela Pontillo (PRIMM S.r.l.) , Cinzia Rigo (PRIMM S.r.l.) , Sandra Abelli (PRIMM S.r.l.) , Romualdo Grande (ASST FBF Sacco) , Nadia Zanchetta (ASST FBF Sacco) , Davide Mileto (ASST FBF Sacco) , Alessandro Mancon (ASST FBF Sacco) , Alberto Rizzo (ASST FBF Sacco) , Alessandro Gori (Consiglio Nazionale delle Ricerche, Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” (SCITEC)) , Marina Cretich (Consiglio Nazionale delle Ricerche, Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” (SCITEC)) , Giorgio Colombo (Consiglio Nazionale delle Ricerche, Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” (SCITEC); Università di Pavia) , Martino Bolognesi (Università degli Studi di Milano) , Louise Jane Gourlay (Università degli Studi di Milano)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Vaccines , VOL 10

State: Published (Approved)
Published: January 2022
Diamond Proposal Number(s): 20221

Abstract: Chagas disease (CD) is a vector-borne parasitosis, caused by the protozoan parasite Trypanosoma cruzi, that affects millions of people worldwide. Although endemic in South America, CD is emerging throughout the world due to climate change and increased immigratory flux of infected people to non-endemic regions. Containing of the diffusion of CD is challenged by the asymptomatic nature of the disease in early infection stages and by the lack of a rapid and effective diagnostic test. With the aim of designing new serodiagnostic molecules to be implemented in a microarray-based diagnostic set-up for early screening of CD, herein, we report the recombinant production of the extracellular domain of a surface membrane antigen from T. cruzi (TcSMP) and confirm its ability to detect plasma antibodies from infected patients. Moreover, we describe its high-resolution (1.62 Å) crystal structure, to which in silico epitope predictions were applied in order to locate the most immunoreactive regions of TcSMP in order to guide the design of epitopes that may be used as an alternative to the full-length antigen for CD diagnosis. Two putative, linear epitopes, belonging to the same immunogenic region, were synthesized as free peptides, and their immunological properties were tested in vitro. Although both peptides were shown to adopt a structural conformation that allowed their recognition by polyclonal antibodies raised against the recombinant protein, they were not serodiagnostic for T. cruzi infections. Nevertheless, they represent good starting points for further iterative structure-based (re)design cycles.

Journal Keywords: Chagas disease; Trypanosoma cruzi; neglected tropical disease; structural vaccinology; peptide microarray; in silico epitope mapping; immunodiagnostics

Diamond Keywords: Chagas Disease

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography

Added On: 12/01/2022 10:28

Documents:
vaccines-10-00071-v2.pdf

Discipline Tags:

Pathogens Infectious Diseases Disease in the Developing World Health & Wellbeing Structural biology Life Sciences & Biotech Parasitology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)