Current Status and Future Challenges for the Development of Genetically Altered Live Attenuated Leishmania Vaccines

Dey, Ranadhir; Gannavaram, Sreenivas; Selvapandiyan, Angamuthu; Fiuza, Jacqueline Araújo; Duncan, Robert C.; Nakhasi, Hira L.

doi:10.1007/978-1-4614-9108-8_4

Cited by 1 publication

(1 citation statement)

References 140 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, growing the attenuated organisms in media containing serum of bovine origin constitutes a possible safety risk due to BSE-related hazard. Our recent studies have shown that the live attenuated L. donovani parasites can be grown in serum free media ( 63 ). The presence of antibiotic markers in the live attenuated organisms can be potential safety concern.…”

Section: Genetically Modified Live Attenuated L Donovani mentioning

confidence: 99%

Biomarkers of Safety and Immune Protection for Genetically Modified Live Attenuated Leishmania Vaccines Against Visceral Leishmaniasis â€“ Discovery and Implications

et al. 2014

Self Cite

View full text Add to dashboard Cite

Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen−/− in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal individuals. In addition, comparative analysis of biomarkers in PBMCs from asymptomatic or healed visceral leishmaniasis individuals in response to vaccine candidates including live attenuated parasites may provide clues about determinants of protective immunity and be helpful in shaping the final Leishmania vaccine formulation in the clinical trials.

show abstract

Section: Genetically Modified Live Attenuated L Donovani mentioning

confidence: 99%