Close
Found 0 results for your search. Showing 0 to 0.
No results could be found for your search.
x Close Search
Close

Messenger RNA vaccines to booster drug efficacy against chronic Chagas disease

Title of PhD project / theme

Messenger RNA vaccines to booster drug efficacy against chronic Chagas disease 

Supervisory team

Nagasaki University
Lead: Prof Kenji Hirayama (hiraken@nagasaki-u.ac.jp)
Dr Daniel Inaoka
Dr Shusaku Mizukami
Prof Katsu Yui  

LSHTM
Prof John Kelly (John.Kelly@lshtm.ac.uk, Faculty of Infectious and Tropical Diseases)

Brief description of project / theme

There are 7 million chronic Chagas disease patients in Latin America, with 39,000 new cases annually, including 9,000 that are congenitally transmitted. (World Health Organization 2015, Chagas diseases in Latin America: an epidemiological update based on 2010 estimates, Weekly epidemiological record, vol. 90, no. 6, pp. 33-44). The front line drugs benznidazole and nifurtimox are curative for acute, but are less effective for chronic infection, and complete parasite clearance can be difficult to achieve. 

Elimination of the parasite can be mediated by two major mechanisms; one is by drug activity, and the second is by the immune response. Therefore, we will attempt to combine immunotherapy and drug treatment. Recently, mRNA vaccines have proved to be effective in inducing B cell and T cell immunity during the COVID-19 pandemic. Using available state of the art technology, we will undertake a proof of concept study of a booster type of vaccine to improve the treatment of this complicated chronic parasitic infection.  

References 

  1. Vásquez VC, Hirayama K et al. IL-17A, a possible biomarker for the evaluation of treatment response in Trypanosoma cruzi infected children: A 12-months follow-up study in Bolivia. PLoS Negl Trop Dis. 2019 Sep 25;13(9): e0007715. 

  1. Tani O, et al. NMR Biochemical Assay for Oxidosqualene Cyclase: Evaluation of Inhibitor Activities on Trypanosoma cruzi and Human Enzymes. J Med Chem. 2018 Jun 14;61(11):5047-5053. Erratum in: J Med Chem. 2018 Jul 26;61(14):6399.  

  1. Cherif MS, Hirayama K.et al. Nanoparticle formulation enhanced protective immunity provoked by PYGPI8p-transamidase related protein (PyTAM) DNA vaccine in Plasmodium yoelii malaria model. Vaccine. 2014 Jan 14. pii: S0264-410X(14)00006-1. 

The role of LSHTM and NU in this collaborative project

The study will be a cooperative project by two institutions, with a history of long-time collaboration. KH and the Nagasaki University group will provide the necessary technology to prepare mRNA vaccines designed to stimulate antibody production and T cell immunity. Nagasaki and LSHTM have a complete facility to maintain and monitor Chagas disease in a mouse model using genetically engineered parasites for the evaluation of treatment efficacy. 

JK and the LSHTM team carry out research on the molecular biology of Trypanosoma cruzi and will support more detailed cellular and pathological analysis of the vaccine trial. Moreover, LSHTM will identify effective target antigens for vaccine design using genes expressed specifically in the tissues of infected mice. 

Particular prior educational requirements for a student undertaking this project

Immunology, Molecular biology, Basic biochemistry, Microbiology 

Skills we expect a student to develop/acquire whilst pursuing this project

  • Preparation of mRNA, cDNA, recombinant proteins 
  • Analysis of DNA, tissue specimen, flowcytometry, single cell mRNA expression 
  • Biological statistics 
  • Scientific logics and communication