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.
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.
APPENDIX 4
Triatoma infestans
Most people, except perhaps entomologists, would describe Triatoma infestans as ugly. It is about one inch long (equal to the combined length of 12,500 T. cruzi trypomastigotes). It has two pairs of long, bent legs covered with fine hairs protruding from an oval-shaped abdomen. A third pair of legs extends like arms from a trapezoidal, horny thorax adjacent to protruding bulbous eyes (see Figure 3). The legs are angularly bent, with thick femurs, long tibias, and short tarsus and nails, enabling it to rapidly move across floors and walls, cling to ceilings, and carry many times its weight in blood. Transparent parchmentlike wings cover the center of its back like a cloak. Extended, they are inadequate for flying, but are used for gliding from heights and for mounting during sex. A pincher-shaped head protrudes from the thorax, with a proboscis folded back underneath which swings down, half-open like a jackknife, to pierce the skin and suck blood.
A principal biological characteristic of Triatoma infestans, as well as other triatomines, is obligate bloodsucking by nymphs and adults of both sexes. Their great success in obtaining blood meals is due primarily to their being nocturnal predators as well as to the biochemical and physiological adaptation of species members to profoundly different ecological niches. They insert their probosces into sleeping mammals, employing a generalized anesthetic so as not to alarm their victims while they leisurely fill up on blood. Different hormones such as ecdysone and juvenile hormones regulate the biochemical and physiological changes in the tegument as they molt and transform through five stages to adulthood.
Blood provides triatomines with a protein- and lipid-rich diet (Brenner 1987). Their metabolism has adapted to this diet, and their energy requirements and ATP (adenosine triphosphate) production are provided
