Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number3c18830
Pages (from-to)15832–15846
Number of pages15
JournalACS Applied Materials and Interfaces
Volume16
Issue number13
DOIs
StatePublished - Apr 3 2024

Keywords

  • Chagas disease
  • biodistribution
  • immunogenicity
  • lipid nanoparticles
  • mRNA vaccine

ASJC Scopus subject areas

  • Materials Science(all)

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