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Review of experimental and observational evidence about various cestode infections of mammalian hosts revives hope for the development of an effective vaccine against adult intestinal tapeworms, the central protagonists in their transmission dynamics. As for Taenia solium, there are abundant immunological data regarding cysticercosis in humans and pigs, but information about human taeniasis is scarce. A single publication reporting protection against T. solium taeniasis by experimental primo infection and by vaccination of an experimental foster host, the immunocompetent female hamster, kindles the hope of a vaccine against the tapeworm to be used in humans, its only natural definitive host.

The disease caused by Taenia solium is progressively being recognized as a growing global threat for public human health and pig husbandry that requires the development of effective control measures. A central participant in the taeniasis/cysticercosis transmission network is the human carrier of the adult tapeworm because of its great potential in spreading the infection. Herein, evidence is presented that a primary infection of golden hamsters with orally administered T. solium cysticerci improved the host's resistance against a secondary infection. Likewise, previous vaccination increased the hamster's resistance. Similar high levels of protection (> 78%) were induced by systemic or oral vaccination with the S3Pvac anticysticercosis synthetic peptide vaccine or the highly immunogenic recombinant chimera based on the protective peptide KETc1 bound to Brucella spp. lumazine synthase (BLS-KETc1). Increased resistance after primo-infection and vaccination possibly results from changes in the immune conditions prevailing in the host's intestine. The contribution to protection from the KETc1 and BLS epitopes in a chimeric vaccine is under study. Preventive vaccination of definitive hosts of T. solium against the tapeworm, the most relevant step in the taeniasis/cysticercosis transmission, may greatly impact the dynamics of endemic disease and has not been studied or tried previously.

Experimental murine cysticercosis caused by Taenia crassiceps has proved to be a useful model with which to test the efficacy of new vaccine candidates and delivery systems against pig cysticercosis. A high level of protection against murine cysticercosis was previously observed by intramuscular or intradermal DNA immunization with the use of the sequence of the recombinant KETc7 antigen cloned in pcDNA3 (pTc-sp7). To determine the effect of KETc7 differential expression in DNA vaccination, KETc7 was cloned in pGEM 11Zf(+) under the control of the tissue-specific regulatory promoter phosphoenolpyruvate carboxykinase (pPc-sp7). A high level of protection was induced by intrahepatic immunization with pPc-sp7, pTc-sp7 and the empty vector in the absence of any specific immunity. The empty vector pGEM 11Zf(+), the plasmid with the highest content of CpG sequences, provided to the most efficient protection. This protection was related to an increased number of splenocytes, enhanced nonspecific splenocyte proliferation, and intensified intrahepatic INF-gamma production. Overall, intrahepatic plasmid CpG-DNA immunization provokes an exacerbated nonspecific immune response that can effectively control Taenia crassiceps cysticercosis.

Untreated Taenia solium cysticerci obtained from different naturally infected pigs vary notably in their capacity to develop into intestinal tapeworms in prednisolone-treated hamsters, whereas cells derived from Taenia crassiceps cysticerci after 2 mo of infection almost always develop to cysticerci in the peritoneal cavity of susceptible BALB/cAnN mice. Preincubation of whole cysticerci or parasite cells with mice immunoglobulins raised against an 18-mer peptide epitope (GK-1) common to both parasites significantly interferes with both transformations. These crippling effects of antiparasite antibodies suggest new forms of immunological interference with parasite biology other than simple killing. Antibodies that cripple biological functions of the parasite, e.g., their development to reproductive or pathogenic stages, make them important protagonists in taeniasis/cysticercosis disease as classic parasitocidal antibodies. Different serum levels of crippling antibodies in the infected pigs could be responsible for the varied ability of cysticerci to convert to tapeworms. Antigens capable of inducing crippling antibodies, e.g., GK-1, could be useful as a therapeutic vaccine for pigs in order to reduce parasite transmission.

The nucleotide sequence of a protective recombinant antigen of Taenia crassiceps cysticerci present in all stages of Taenia solium (KETc7), cloned into pcDNA3 plasmid with the signal peptide sequence of the beta-glycan receptor (pTc-sp7), has been shown to be effective in protecting mice against experimental infection of T. crassiceps. To explore further the possibilities of this form of immunization and the immune response induced, mice were injected intramuscularly (i.m.) or intradermally (i.d.) with 3 doses of pTc-sp7. Similar levels of resistance were found using either i.m. or i.d. immunization. Spleen cells from i.d. and i.m. DNA immunized mice induced a specific T-cell response to T. crassiceps antigens and to a synthetic peptide from the immunogen itself (GK-1). Proliferated cells were especially enriched in CD8+ CD4- T-lymphocytes. A clear increase in the percentage of CD3+ cells that produce gamma-interferon and interleukin-2 was detected when measuring the intracellular cytokine production, an indication of the pTc-sp7 capacity to induce an effective cellular response. These results provide encouraging information on the use of KETc7 in the prevention of cysticercosis as well as a first insight into the characterization of the immune response induced by pTc-sp7 that hints to the relevance of cellular immunity in protection.

The purpose of this study was to evaluate DNA vaccination in cysticercosis prevention by using a Taenia crassiceps cDNA of a recombinant antigen (KETc7) that has been reported as protective against murine cysticercosis. The KETc7 cDNA was cloned into the pcDNA3 plasmid alone or with the betaglycan signal peptide sequence (pTc-7 and pTc-sp7, respectively). Positive expression of the pTc-sp7 product was confirmed by transfection of C33 cells and immunofluorescence using sera of mice infected with T. crassiceps. Immunization of mice with 3 injections of pTc-sp7 DNA at the higher dose (200 microg) was the most effective to induce antibody with or without bupivacaine. Immunization with pTc-sp7 induced protection against challenge with T. crassiceps cysticerci as successfully as previously observed with the KETc7 recombinant protein. Antibodies elicited by DNA immunization with pTc-sp7 specifically reacted with the native protein of 56 kDa previously reported, which is immunolocalized in the tegument of T. crassiceps cysticerci. The 56-kDa antigen is also present in Taenia solium oncospheres, cysticerci, and adult tissue. The protection induced in DNA-immunized mice and the observation that the injected plasmid remains as an episomic form within muscle cells, encouraged us to continue testing this procedure to prevent T. solium cysticercosis.