Enhanced Protective Efficacy of Nonpathogenic Recombinant Leishmania tarentolae Expressing Cysteine Proteinases Combined with a Sand Fly Salivary Antigen

Abstract

BackgroundNovel vaccination approaches are needed to prevent leishmaniasis. Live attenuated vaccines are the gold standard for protection against intracellular pathogens such as Leishmania and there have been new developments in this field. The nonpathogenic to humans lizard protozoan parasite, Leishmania (L) tarentolae, has been used effectively as a vaccine platform against visceral leishmaniasis in experimental animal models. Correspondingly, pre-exposure to sand fly saliva or immunization with a salivary protein has been shown to protect mice against cutaneous leishmaniasis.Methodology/Principal FindingsHere, we tested the efficacy of a novel combination of established protective parasite antigens expressed by L. tarentolae together with a sand fly salivary antigen as a vaccine strategy against L. major infection. The immunogenicity and protective efficacy of different DNA/Live and Live/Live prime-boost vaccination modalities with live recombinant L. tarentolae stably expressing cysteine proteinases (type I and II, CPA/CPB) and PpSP15, an immunogenic salivary protein from Phlebotomus papatasi, a natural vector of L. major, were tested both in susceptible BALB/c and resistant C57BL/6 mice. Both humoral and cellular immune responses were assessed before challenge and at 3 and 10 weeks after Leishmania infection. In both strains of mice, the strongest protective effect was observed when priming with PpSP15 DNA and boosting with PpSP15 DNA and live recombinant L. tarentolae stably expressing cysteine proteinase genes.Conclusion/SignificanceThe present study is the first to use a combination of recombinant L. tarentolae with a sand fly salivary antigen (PpSP15) and represents a novel promising vaccination approach against leishmaniasis.

Assessment of Protection Induced by DNA and Live Vaccine Encoding Leishmania MHC Class I Restricted Epitopes against L. major Challenge in Balb/c Mice Model

“…Previously L. tarentolae has proven promising by long lasting protection while expressing multiple candidate antigens (all among potential vaccine candidates as A2) [24,48] especially along with sandfly salivary immune-stimulatory proteins [49]. This is a confirmatory proof that peptides included must be among high avidity ones previously evaluated in in vivo infectious challenge.…”

A sand fly salivary protein vaccine shows efficacy against vector-transmitted cutaneous leishmaniasis in nonhuman primates

“…In combination with parasite antigen/s, targeting vector-derived molecules as a component of Leishmania vaccines presents an opportunity to improve their effectiveness. In a recent study, using various vaccine modalities of PpSP15 DNA, a T H 1-DTH-inducing salivary protein from P. papatasi that protected mice from L. major infection as a DNA vaccine (3,6), and live recombinant Leishmania tarentolae stably expressing cysteine proteinase genes (17), the strongest protective effect was observed when priming with PpSP15 DNA and boosting with PpSP15 DNA plus the recombinant parasite (18), suggesting that priming with a sand fly salivary protein and boosting with the salivary protein in the presence of a Leishmania antigen may improve protective immunity.…”

Vaxvec: The first web-based recombinant vaccine vector database and its data analysis

“…The nonpathogenic lizard protozoan parasite L. tarentolae has been used as a vector for three vaccines against L. infantum infection [39], L. major infection [40], and HIV-1 infection [41]. The safe and stable S. cerevisiae yeast vaccine vector has been used to develop two oral vaccines against porcine pleuropneumonia [42, 43].…”