Oxidative stress implications for therapeutic vaccine development against Chagas disease

ABSTRACT

Introduction

Pathogenesis of Chagas disease (CD) caused by the protozoan parasite Trypanosoma cruzi (T. cruzi) involves chronic oxidative and inflammatory stress. In this review, we discuss the research efforts in therapeutic vaccine development to date and the potential challenges imposed by oxidative stress in achieving an efficient therapeutic vaccine against CD.

Areas covered

This review covers the immune and nonimmune mechanisms of reactive oxygen species production and immune response patterns during T. cruzi infection in CD. A discussion on immunotherapy development efforts, the efficacy of antigen-based immune therapies against T. cruzi, and the role of antioxidants as adjuvants is discussed to provide promising insights to developing future treatment strategies against CD.

Expert opinion

Administration of therapeutic vaccines can be a good option to confront persistent parasitemia in CD by achieving a rapid, short-lived stimulation of type 1 cell-mediated immunity. At the same time, adjunct therapies could play a critical role in the preservation of mitochondrial metabolism and cardiac muscle contractility in CD. We propose combined therapy with antigen-based vaccine and small molecules to control the pathological oxidative insult would be effective in the conservation of cardiac structure and function in CD.

KEYWORDS:

• Chagas disease
• immunity
• oxidative stress
• reactive oxygen species
• Trypanosoma cruzi
• therapeutic vaccine

Article highlights

• Trypanosoma cruzi infection and Chagas disease remain major health concerns in the Americas.

• There is a critical lack of methods for prevention of infection or treatment of chronic Chagas disease.

• Immune therapies or therapeutic vaccines that can control T. cruzi persistence and associated disease pathology must be a public health priority.

• Multi-faceted nature of Chagas disease requires that immune therapies targeting the parasite persistence should be conjugated with adjuvants to address chronic inflammation and oxidative stress.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors substantially contributed to the conception and design of the review article and interpreting the relevant literature. All authors were involved in writing the review article and in revising it for intellectual content.

Additional information

Funding

This work was supported, in part, by a grant from the National Institute of Allergy and Infectious Diseases (R01AI136031) of the National Institutes of Health to NJG. The funders had no role in decision to publish or preparation of the manuscript. LR is the recipient of pre-doc fellowship from the Sealy Institute for Vaccine Studies and Zelda Zinn Casper Scholars Endowment at the UTMB Galveston. JCVC is sponsored by SIEA-UAEM project # 6224/2020 CIB.