Trypanosoma cruzi trans-Sialidase as a Potential Vaccine Target Against Chagas Disease

Abstract

Chagas’ disease is caused by the protozoan Trypanosoma cruzi, described in the early 20th century by the Brazilian physician Dr. Carlos Chagas. There was a great amount of research devoted to diagnosis, treatment and prevention of the disease. One of the most important discoveries made since then, impacting the understanding of how the parasite interacts with the host’s immune system, was the description of trans-sialidase. It is an unique enzyme, capable of masking the parasite’s presence from the host, while at the same time dampening the activation of CD8+ T cells, the most important components of the immune response. Since the description of Chagas’ disease in 1909, extensive research has identified important events in the disease in order to understand the biochemical mechanism that modulates T. cruzi-host cell interactions and the ability of the parasite to ensure its survival. The importance of the trans-sialidase enzyme brought life to many studies for the design of diagnostic tests, drugs and vaccines. While many groups have been prolific, such efforts have encountered problems, among them: the fact that while T. cruzi have many genes that are unique to the parasite, it relies on multiple copies of them and the difficulty in providing epitopes that result in effective and robust immune responses. In this review, we aim to convey the importance of trans-sialidase as well as to provide a history, including the initial failures and the most promising successes in the chasing of a working vaccine for a disease that is endemic in many tropical countries, including Brazil.

Leishmaniasis and Chagas disease: Is there hope in nanotechnology to fight neglected tropical diseases?

“…Several T. cruzi proteins are able to promote cardiac damage in the absence of live parasites by inducing autoimmunity in animal models (Cunha-Neto et al, 1996;Bonney et al, 2011). Fortunately, a number of other recombinant T. cruzi proteins as well as attenuated T. cruzi parasites are emerging as potentially safe strategies for the development of a CD vaccine (Sańchez-Valdeź et al, 2015;Rios et al, 2019;da Costa et al, 2021;Rodrigues da Cunha et al, 2021). Researchers are also testing mRNA vaccines after their successful use in COVID-19 (Diaz-Hernandez et al, 2022;Maldonado et al, 2022).…”

The high identity of the Trypanosoma cruziGroup‐I of trans‐sialidases points them as promising vaccine immunogens

“…Moreover, studies of TSsf-based vaccines have been performed in other animal models like dogs [50][51][52] or monkeys 53 ; however, although promising, they are not enough to reach conclusive results. Within this family, TS-GI proteins have been signaled highly promising candidates (revised by da Costa et al 12 ). However, unlike studies performed with TS-GII, the variability of these antigens was not previously analyzed.…”

“…For the TS-GII, which are also among the most used as vaccine antigens, studies about diversity and its possible influence on vaccine performance have been reported only in two studies. 10,11 The TS-GI proteins have also been widely tested as immunogens for T. cruzi vaccines, and they have been pointed out as very promising candidates, 12 however, their diversity has not been analyzed in the context of vaccine development. Moreover, vaccine antigen epitopes should ideally be recognized by the whole HLA diversity of the human population to be protected.…”

Extracellular Vesicles: Translational Agenda Questions for Three Protozoan Parasites

“…Vaccines for the prevention and control of T. cruzi infection may also be developed using molecules released in EVs. The proteins of T. cruzi ‐derived EVs have been identified as potential vaccine candidates, including members of the TS family, which are involved in invasion processes [48], and the T. cruzi trypomastigote alanine, valine and serine (TcTASV‐C) protein, which plays a role in immune evasion and host–parasite interactions [49]. While these proteins have not yet shown promise as vaccine candidates, the mucin‐like‐associated surface protein (MASP) family, a virulence factor involved in host‐cell invasion, has shown the ability to induce a humoral and cellular response and reduce parasite load when used in immunisation of mice [50].…”