Prospects for Immunizations

The facts that most of the pathology from Chagas’ disease relates to the immune response and that living organisms are necessary for acquired partial immunity present slim possibilities for developing a vaccine against Chagas’ disease. To produce a vaccine for Chagas’ disease, the following requirements are necessary:

1) Any vaccine should not induce active infection; therefore, immunization with living T. cruzi is out of the question. Reasons include the facts that even weaker strains could elicit autoimmune pathology and that weaker strains are not found, only less virulent strains. Moreover, the risk would be much too great to be undertaken by international health organizations.

2) Any vaccine must confer total and sterile protection. Vaccines that have been tried in mice employing either live and attenuated (weakened) parasites, killed intact organisms, or cell homogenates were able only to delay mortality. These vaccines produce partial protection from acute infections and do not provide protection from chronic infections, which in some cases are a more horrible way to die. Nonetheless, partial protection may be important to prevent the high incidence of deaths of children from acute infections.

3) Any vaccine cannot induce an autoimmune response, so the vaccine has to be very specific and exclusionary in targeting only parasite antigens and not those that the parasite shares with the host. Any misdirection could lead to creating EVI antibodies that are in themselves sources of pathology in the host. Moreover, the targeted parasite antigen must be essential to the parasite and on its surface throughout its trypomastigote and amastigote forms. This implies highly complicated research and very involved testing of vaccines, with the result most likely being high‑cost vaccine production that will be unaffordable to people in endemic areas.

If and when a suitable antigen is found and vaccines are developed with it, there are most likely some strains of T. cruzi to which the chosen antigen may be ineffective in inducing protective immunity. Even if all strains are affected, there will be mutant individuals which the vaccine will not affect, leading to the evolution of resistant strains of the parasite. These “super” T. cruzi will continue on.

4) Any vaccine should not be immunosuppressive. Because T. cruzi antigens induce polyclonal activation, they are followed by a period of immunosuppression. Implications are that if children are vaccinated and immunosuppression follows, they are subject to other infections. A related problem is that polyclonal activation can also cause severe inflammation, lesions, and fever.

Conclusions include that a vaccine for T. cruzi cannot be a crude extract, and that to fulfill the above criteria the vaccine is going to have to feature a highly sophisticated, very carefully selected, and very specific and essential antigen of T. cruzi found on all its forms. Moreover, the antibodies produced from this vaccine antigen must be able to destroy 100 percent of trypomastigotes within minutes after the bite of a triatomine bug. If one trypomastigote gets into a cell, it can reproduce there and establish an infection.

Regarding Bolivia and many tropical areas, administration of such a vaccine will be difficult because of its inevitable high cost. Vaccine administration in underdeveloped countries is a problem; improper storage and/or administration can result in contamination or destruction of the vaccine or its selection for resistant individuals in parasite populations.