Abstract
BackgroundToxoplasma gondii, an obligate intracellular apicomplexan parasite, infects a wide range of warm-blooded animals including humans. T. gondii expresses five members of the C1 family of cysteine proteases, including cathepsin B-like (TgCPB) and cathepsin L-like (TgCPL) proteins. TgCPB is involved in ROP protein maturation and parasite invasion, whereas TgCPL contributes to proteolytic maturation of proTgM2AP and proTgMIC3. TgCPL is also associated with the residual body in the parasitophorous vacuole after cell division has occurred. Both of these proteases are potential therapeutic targets in T. gondii. The aim of this study was to investigate TgCPB and TgCPL for their potential as DNA vaccines against T. gondii.MethodsUsing bioinformatics approaches, we analyzed TgCPB and TgCPL proteins and identified several linear-B cell epitopes and potential Th-cell epitopes in them. Based on these results, we assembled two single-gene constructs (TgCPB and TgCPL) and a multi-gene construct (pTgCPB/TgCPL) with which to immunize BALB/c mice and test their effectiveness as DNA vaccines.ResultsTgCPB and TgCPL vaccines elicited strong humoral and cellular immune responses in mice, both of which were Th-1 cell mediated. In addition, all of the vaccines protected the mice against infection with virulent T. gondii RH tachyzoites, with the multi-gene vaccine (pTgCPB/TgCPL) providing the highest level of protection.ConclusionsT. gondii CPB and CPL proteases are strong candidates for development as novel DNA vaccines.
Highlights
Toxoplasma gondii, an obligate intracellular apicomplexan parasite, infects a wide range of warmblooded animals including humans
We propose that a DNA vaccine construct based on TgCPB and TgCPL could be a useful tool against disease caused by T. gondii
Thereafter, we made single-gene and multi-gene DNA vaccines to evaluate the level of immunoprotection induced in mice immunized with such vaccines
Summary
Toxoplasma gondii, an obligate intracellular apicomplexan parasite, infects a wide range of warmblooded animals including humans. TgCPL is associated with the residual body in the parasitophorous vacuole after cell division has occurred Both of these proteases are potential therapeutic targets in T. gondii. TgCPB and TgCPL are mainly expressed in the vacuolar compartment, but a tiny amount of TgCPL has been identified in the late endosome [16,17,18,19] These proteases are thought to function in protein degradation and play specialized roles in the maturation of invasion-related proteins. TgCPL contributes to proteolytic maturation of proTgM2AP and proTgMIC3, and is associated with the residual body in the parasitophorous vacuole after cell division [20,21,22,23]
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