Testing of FourLeishmaniaVaccine Candidates in a Mouse Model of Infection withLeishmania(Viannia)braziliensis, the Main Causative Agent of Cutaneous Leishmaniasis in the New World

Abstract

We evaluated whether four recombinant antigens previously used for vaccination against experimental infection with Leishmania (Leishmania) major could also induce protective immunity against a challenge with Leishmania ( The protozoan parasite Leishmania (Viannia) braziliensis commonly causes localized cutaneous leishmaniasis (CL); however, a chronic mucosal leishmaniasis (ML) may develop in some infected individuals, with severe and progressive manifestations (reviewed in reference 11). At present, this species accounts for more than 90% of the 28,712 annual cases of CL and ML recorded in Brazil in 2004 (7). Although chemotherapies for CL and ML do exist, there are several limitations: (i) drug treatment is rarely affordable by those who need them, (ii) drug treatment requires daily injections of the drug for weeks, (iii) drug treatment can be associated with side effects, and (iv) drug resistance is becoming an increasing problem (13, 24; reviewed in references 3 and 32). To make matters worse, control of CL and ML is problematic due to the sylvatic nature of both vectors and reservoirs, making insecticide spraying and the elimination of reservoirs particularly difficult (26). Due to these difficulties, in the long run, the development of an effective vaccine may help both the prevention and the treatment of CL and ML caused by L. (V.) braziliensis.Most studies conducted thus far in vaccination against CL used genes and/or antigens isolated and characterized from Leishmania (Leishmania) major or L. (L.) amazonensis (8, 31; reviewed in references 9 and 21). Among the leading candidates to the development of a vaccine against CL, there are homologues of the receptor for activated C kinase protein (LACK or p36), Leishmania elongation and initiation factor (LeIF), L. (L.) major stress inducible protein 1 (LmSTI1), and thiol-specific antioxidant (TSA) from L. (L.) major (5, 6, 10, 14, 15, 28, and 30).Based on these promising prospects, the present study was designed to test whether four recombinant antigens previously used for vaccination against experimental infection with L. (L.) major (LACK, LmSTI1, LeIF, and TSA) could also generate protective immunity against an intradermal (i.d.) challenge with L. (V.) braziliensis. We considered this question very important because, as mentioned above, this species is responsible for most cases of CL and ML in Brazil and in the New World.

Immunogenicity and efficacy of recombinant 78 kDa antigen of Leishmania donovani formulated in various adjuvants against murine visceral leishmaniasis

“…In contrast to our study where immunization with liposome-encapsulated r78 was slightly more effective in reducing the parasite burden as compared to r78 given along with MPL-A, vaccination with liposomal rGP63 along with MPL-TDM showed almost 2-logfold, and 7-10-log-fold reduction in parasite burden compared to mice boosted with liposomal rGP63 and unvaccinated mice, respectively [21] . However, immunization with recombinant isolates of LeIF, LmSTI1 and TSA from Leishmania braziliensis (L. braziliensis) individually or in combination did not protect mice against challenge infection with L. braziliensis despite the induction of antibody and cell mediated responses [22].…”

Vaccine candidates for leishmaniasis: A review

“…However, immunization with recombinant isolates of LeIF, LmSTI1 and TSA from L. braziliensis individually or in combination did not protect mice against challenge infection with L. braziliensis despite the induction of antibody and cell mediated responses [252]. The mixture of recombinant components of Leish-111f was highly immunogenic in dogs [253] but failed to protect them against L. infantum infection and did not prevent disease development in a phase III trial in dogs [114,254].…”

Protective Immunity and Vaccination Against Cutaneous Leishmaniasis

“…Recently a polyprotein vaccine made up of LACK, TSA, LbSTI, or LeIF was shown to protect mice against CL caused by L. major but failed to protect disease caused by L. braziliensis (Salay et al, 2007). This result is rather puzzling given that the vaccine consisted of components derived from antigens that are conserved across all Leishmania and hence should cross protect against different Leishmania species.…”