AUTHOR=Cai Catherine W. , O’Shea Anne , Eickhoff Christopher S. , Guo Hongjie , Lewis Warren G. , Beverley Stephen M. , Hoft Daniel F. 

TITLE=Use of Leishmania major parasites expressing a recombinant Trypanosoma cruzi antigen as live vaccines against Chagas disease

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1059115

DOI=10.3389/fmicb.2022.1059115

ISSN=1664-302X

ABSTRACT=<sec><title>Introduction</title><p><italic>Trypanosoma cruzi</italic> is the protozoan parasite causing Chagas disease, a Neglected Tropical Disease that affects 8 million people and causes 12,000 deaths per year, primarily because of cardiac pathology. Effective vaccination for <italic>T. cruzi</italic> remains an elusive goal. The use of a live vaccine vector, especially one that mimics the pathogen target, may be superior to the use of recombinant protein or DNA vaccine formulations.</p></sec><sec><title>Methods</title><p>We generated recombinant <italic>Leishmania major</italic>, a related trypanosomatid parasite, as a vaccine vehicle to express the immunogenic <italic>T. cruzi trans</italic>-sialidase (TS) antigen. The induction of T cell and antibody responses, as well as <italic>T. cruzi</italic> protective immunity generated by these vaccines were assessed in vivo.</p></sec><sec><title>Results</title><p>We demonstrate that mice inoculated with these recombinant TS-expressing <italic>L. major</italic> parasites mount T cell and antibody responses directed against TS and are protected against future <italic>T. cruzi</italic> infection. We also show that the partially attenuated <italic>dhfr-ts- CC1 L</italic>. major strain, previously found to induce protective immunity to virulent <italic>L. major</italic> infection without causing pathology, can also be engineered to express the TS antigen. This latter recombinant may represent a safe and effective option to explore for ultimate use in humans.</p></sec><sec><title>Discussion</title><p>Altogether, these data indicate that <italic>L. major</italic> can stably express a <italic>T. cruzi</italic> antigen and induce <italic>T. cruzi</italic>-specific protective immunity, warranting further investigation of attenuated Leishmania parasites as vaccine.</p></sec>