The Nucleoside hydrolase DNA vaccine VR1012NH36 in prophylactic vaccination against mice tegumentar leishmaniasis

The VR1012NH36 DNA vaccine was immunoprophylactic and immunotherapeutic against mice visceral leishmaniasis by L.(L.) chagasi and cutaneous leishmaniasis by L. (L.) mexicana. We here evaluated the protection induced by three sc doses of FML (150 μg) + saponin (100 μg), or two doses of VR1012 empty plasmid (100 μg) or VR1012NH36 (100 μg) vaccine against the footpad L. (L.) amazonensis infection with 1 million promastigotes. After infection, the anti-FML IgG, IgG1 and IgG2a antibodies were significantly increased over the saline controls only in the FML saponin vaccinated animals. The DTH response against L.(L.) amazonesis lysate was increased by both vaccines over the saline controls before infection. Regarding the reduction of parasite lesions, at week 26 after infection, significant differences were found in the footpad swelling (ANOVA; p=0.004). Protection was measured as the reduction in footpad swelling. Considering the mean values of each group as well as the individual results, the highest protection was determined by the DNA vaccine followed by the FML saponin vaccine. The DNA vaccine induced 80.4%, the empty plasmid 26.5% and the FML vaccine, 49% of reduction (p<0.05) indicating antigen-specific protection. Indeed, the increase in footpad sizes was detected in 5 of 7 mice treated with saline, 3 treated with empty plasmid, in 1 treated with the FML and in only 2 treated with the NH36 DNA vaccine. Noteworthy, the increase in the NH36 DNA treated mice started on week 26 while in other groups, between weeks 12-14. At the end of the assay, on week 33, survival was 90% for the DNA vaccine group and 70% for the empty plasmid, FMLSAP and saline treated animals. Of note, while deaths begun at week 12 in other groups, the only obit in the DNA vaccinated animals occurred at week 33. Our results point out that the NH36 gene of L. (L.) donovani, as a DNA vaccine, followed by the FMLSAP vaccine, induce significant cross-protective response against tegumentar leishmaniasis induced by L.(L.) amazonensis, indicating its potential use as a bivalent vaccine against visceral and tegumentar leishmaniasis.