"FROM GENOMES TO VACCINES: A REVERSE VACCINOLOGY APPROACH AGAINST LEISHMANIA SPP."
Disertante: Lic. Rocío Cenizo - becaria doctoral CONICET
Director: Dr. Augusto Ernesto Bivona
Co-director: Dr. Emilio Luis Malchiodi
Resumen:
Leishmaniasis are parasitic diseases caused by Leishmania spp., transmitted to humans through sandfly bites. Depending on the Leishmania species involved and the host's immune status, the clinical manifestations vary, from mild, self-healing skin ulcers (cutaneous leishmaniasis, CL) to the potentially fatal visceral leishmaniasis. Current treatments are expensive, highly toxic, and involve complex regimens. Considering these limitations, vaccination has emerged as a promising, cost-effective solution, however, no vaccines have been approved for humans yet, and the experimental vaccines evaluated to date have shown limited and variable efficacy. Here, we propose a reverse vaccinology approach to identify new immunogens that could protect against different forms of leishmaniasis.
Five vaccine targets were identified from annotated Leishmania proteomes, considering protein conservation, transcriptomic data, epitope predictions, and subcellular localization. These genes were cloned into the pVAX1 vector, and their expression in vitro was confirmed by immunofluorescence. All candidates (L1-L5) were subsequently evaluated as prophylactic vaccines in a CL model. Groups of BALB/c mice received three intramuscular doses, administered every 28 days of 100 µg pVAX1 encoding one candidate or empty pVAX1 vector as control. Twenty-two days after the final dose, mice were challenged on the left hind footpad with fluorescent-tagged Leishmania amazonensis. Footpad thickness was measured weekly to monitor infection, and the parasite loads were analyzed using in vivo fluorescence imaging.
The in vitro expression of all identified candidates was successfully demonstrated. The five candidates tested as prophylactic vaccine significantly reduced lesion size compared to the control (p<0.005), with Ag3 and Ag5 showing the best performance, 5 and 3-fold reduction, respectively. These results correlated with the parasitic load measured by in vivo fluorescence imaging.
These results demonstrate the potential of reverse vaccinology in the discovery of immunogens capable of conferring protection against leishmaniasis in a preclinical model of the disease.
Los esperamos el próximo lunes 11 de mayo a las 12.30 hs en el aula del piso 13 de nuestra facultad.
