Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease

Authors

Chiara Mancino
Jeroen Pollet
Assaf Zinger
Kathryn M Jones
Maria José Villar
Ana Carolina Leao
Rakesh Adhikari
Leroy Versteeg
Rakhi Tyagi Kundu
Ulrich Strych
Federica Giordano
Peter J Hotez
Maria Elena Bottazzi
Francesca Taraballi
Cristina Poveda

Publication Date

4-3-2024

Journal

ACS Applied Materials & Interfaces

DOI

10.1021/acsami.3c18830

PMID

38518375

PMCID

PMC10996878

PubMedCentral® Posted Date

3-22-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Mice, Animals, RNA, Tissue Distribution, Protozoan Vaccines, Chagas Disease, Antigens, Protozoan, RNA, Messenger, Technology, Chagas disease, mRNA vaccine, lipid nanoparticles, biodistribution, immunogenicity

Abstract

Chagas disease (CD) (American trypanosomiasis caused by Trypanosoma cruzi) is a parasitic disease endemic in 21 countries in South America, with increasing global spread. When administered late in the infection, the current antiparasitic drugs do not prevent the onset of cardiac illness leading to chronic Chagasic cardiomyopathy. Therefore, new therapeutic vaccines or immunotherapies are under development using multiple platforms. In this study, we assessed the feasibility of developing an mRNA-based therapeutic CD vaccine targeting two known T. cruzi vaccine antigens (Tc24—a flagellar antigen and ASP-2—an amastigote antigen). We present the mRNA engineering steps, preparation, and stability of the lipid nanoparticles and evaluation of their uptake by dendritic cells, as well as their biodistribution in c57BL/J mice. Furthermore, we assessed the immunogenicity and efficacy of two mRNA-based candidates as monovalent and bivalent vaccine strategies using an in vivo chronic mouse model of CD. Our results show several therapeutic benefits, including reductions in parasite burdens and cardiac inflammation, with each mRNA antigen, especially with the mRNA encoding Tc24, and Tc24 in combination with ASP-2. Therefore, our findings demonstrate the potential of mRNA-based vaccines as a therapeutic option for CD and highlight the opportunities for developing multivalent vaccines using this approach.