Prime-boost vaccination using cysteine proteinases type I and II of Leishmania infantum confers protective immunity in murine visceral leishmaniasis

Protective immunization against visceral leishmaniasis using Leishmania sterol 24-c-methyltransferase formulated in adjuvant

“…There have been a limited number of vaccine candidates which have been shown to induce protection against VL in animal models [21][22][23]27]. In this study, we demonstrated that immunization with L. infantum SMT plus MPL ® -SE induced a mixture of Th1 and Th2 responses to the vaccine antigen and significantly protected mice from L. infantum, a causative agent of VL in humans and dogs.…”

“…There is also progress in characterization of defined antigens protective against VL in animal models as sub-unit or DNA vaccines such as KMP11, HASPB, A2 and CPB [21][22][23][24][25][26][27], whereas there are still only a limited number of bona fide vaccine candidates to combat this disease and no vaccine is available for human use yet. We have recently identified a number of L. infantum Ags by serological screening using sera from L. infantum-infected hamsters [28].…”

KSAC, the First Defined Polyprotein Vaccine Candidate for Visceral Leishmaniasis

“…A2, on the other hand, lacked its first 26 amino acids; these amino acids were predicted by the SignalP 3.0 software program (4) to comprise the signal peptide. The partial CPB sequence (amino acids [aa] 128 to 443) in our KSAC construct is the same one shown to be protective in previous studies (34,36). KSAC was expressed in E. coli and purified to homogeneity using two orthogonal chromatographic steps.…”

“…Those antigens, which include a Leishmania homolog of receptors for activated C kinase (LACK), GP63, thiol-specific antigen (TSA), hydrophilic acylated surface protein B (HASPB), sterol 24-c-methyltransferase (SMT), kinetoplastid membrane protein 11 (KMP11), A2, and cysteine proteinase B (CPB), confer protection against disease in different animal models of leishmaniasis (3,14,16,28,36,37,44,46). Because of the genetic polymorphism in the mammalian immune system, a vaccine composed of multiple antigens rather than a single gene product is more likely to elicit a protective immune response against leishmaniasis in a broad spectrum of individuals.…”

“…In this study we focused on several proteins previously demonstrated to be protective against VL in animal models, including dogs, and recognized in humans cured from VL (22). The proteins KMP-11 (3), SMT (16), A2 (13,14), and CPB (34,36) were genetically fused to produce a single multiepitope product developed with the goal of achieving a cost-effective product with maximum efficacy. We evaluated protective efficacy of the resulting polyprotein in two different experimental murine leishmaniases, CL and VL.…”