Journal of Vaccines & Vaccination

Ex vivo studies for pre-clinical evaluation of genetically modified live attenuated Leishmania parasites as potential vaccine candidate against visceral leishmaniasis in human blood PBMCs

12^th Asia Pacific Global Summit and Expo on Vaccines & Vaccination

November 24-25, 2016 Melbourne, Australia

Poonam Salotra, Kumar Avishek, Himanshu Kaushal, Sreenivas Gannavaram, Ranadhir Dey, Angamuthu Selvapandiyan, V Ramesh, Narender Singh Negi and Hira L Nakhasi

National Institute of Pathology, India
Center for Biologics Evaluation and Research, USA
Jamia Hamdard, India
Vardhman Mahavir Medical College and Safdarjung Hospital, India

Posters & Accepted Abstracts: J Vaccines Vaccin

Abstract:

Visceral leishmaniasis (VL) is one of the world�??s most neglected and deadliest parasitic diseases, second only to malaria, endemic in 88 countries worldwide. Currently no effective vaccine is available for the potentially fatal disease, visceral leishmaniasis (VL) caused by protozoan parasites of Leishmania donovani complex. We have developed two genetically defined live attenuated Leishmania donovani parasites, one lacking centrin1, a growth regulating gene (Ldcen1-/-) and another lacking p27 gene (Ldp27-/-), an essential component of cytochrome c oxidase complex, involved in oxidative phosphorylation. Both vaccine candidates have been demonstrated as safe, immunogenic and protective in animal models. Here, we studied the immune responses generated by these mutant parasites in human PBMCs obtained from healed VL (HVL, n=15), post kalaazar dermal leishmaniasis (PKDL, n=15), VL (n=7) and healthy individuals (n=15). The infectivity of mutant parasites to human macrophages was similar to the wild type parasite. Further, Ldcen1-/- and Ldp27-/- strongly stimulated production of pro-inflammatory cytokines including, IL-12, IFN-γ, TNF-α, IL-2, IL-6 and IL-17 in the PBMCs obtained from individuals with a prior exposure to Leishmania (HVL and PKDL); however, no significant stimulation was found in anti-inflammatory cytokines (IL-4 and IL-10). This Th1 biased response was further supported by a remarkable increase in IFN-γ secreting CD4+ and CD8+ T cells and IL-17 secreting CD4+ cells while there was no increase in IL-10 secreting CD4+ and CD8+ T cells in PBMCs from HVL blood. These results suggest that Ldcen1-/- and Ldp27-/- are both promising vaccine candidates against VL since they elicit strong protective immune response in human PBMCs from HVL, similar to the wild type parasite infection, mimicking a naturally acquired protection following cure.

Biography :

Email: salotra@vsnl.com