Antigenic Targets for Immunizations

 

Glycoprotein (GP) antigens found on T. cruzi’s coat are considered as antigenic targets for immunizations. Because GP‑90 is found in all stages of T. cruzi’s life cycle, it may be a candidate target of a vaccine against the parasite. Experimentally, acutely infected chagasic mice were vaccinated with such an antibody and did not die; however, they remained infected. Although this vaccine may be suitable to curtail the ravages of acute infection in infants, it is less than adequate for adults who are suffering with chronic infections.

Because GP‑72 is found on the surface of infective trypomastigotes, it would be a good antigen to target in the development of a vaccine. The function of GP‑72 is demonstrated by the fact that if GP‑72 is stripped from the surface of epimastigotes, they are unable to transform into metacyclic trypomastigotes. GP‑72 is essential for this transformation process.

Entomologically, GP‑72 is valuable for the making of maps plotted according to geographical areas where various strains (zymodemes) of T. cruzi are found. The pathology of Chagas’ disease is related to zymodemes. From the different regions of Bolivia, triatomines are collected, epimastigotes extracted from infected bugs, and GP‑72 measured. This provides a guide to the prevalent strains and pathologies in the departments of Bolivia. Glycoprotein GP‑25 is useful in immunodiagnosis and appears on epimastigotes and trypomastigotes.

Another possibility for vaccine involves GP‑85, which is thought to be a glycoprotein that allows the parasite to attach itself to the host’s cell membranes. If a vaccine can destroy GP‑85, the parasite cannot penetrate and attach itself to cells.

With any of these possibilities, a major problem is that antibodies specific to T. cruzi antigens also cross‑react with human host cells. Therefore, even if it worked in mice, there is the possibility that a vaccine may aggravate the situation by inducing antibodies that cross‑react with host cell antigens. Autoimmunity is considered to play a central role in the pathology of Chagas’ disease.

Conclusions from research on various biochemical coatings on surfaces of T. cruzi indicate that immunoprophylaxis does not appear to be possible for the following reasons (Snary 1985:144‑48): scientists have not found a vaccine that induces sterile immunity, and, furthermore, in regard to experimental vaccines, scientists have not established that those tested would not also induce autoantibody production in the host.

The conclusion is that Trypanosoma cruzi has evolved to fit an intricately complex niche in the organic world. The biology of this organism is complex, involving intimate interactions with two different hosts which include a variety of different life‑cycle stages that exhibit major differences in structural and functional biochemistry. The organism’s survival involves highly successful evasive strategies against the human immune system as well as the extraordinary ability to survive in a variety of hostile environments inside insects and humans and to make use of the complex relationship between insects and mammals in the reproduction and transmission of the species.

 








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