Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/12653
Title: Vaccination using live attenuated Leishmania donovani centrin deleted parasites induces protection in dogs against Leishmania infantum
Authors: Fiuza, Jacqueline Araújo
Gannavaram, Sreenivas
Santiago, Helton da Costa
Selvapandiyan, Angamuthu
Souza, Daniel Menezes
Passos, Lívia Silva Araújo
Mendonça, Ludmila Zanandreis de
Giunchetti, Denise da Silveira Lemos
Ricci, Natasha Delaqua
Bartholomeu, Daniella Castanheira
Giunchetti, Rodolfo Cordeiro
Bueno, Lilian Lacerda
Oliveira, Rodrigo Correa de
Nakhasi, Hira L.
Fujiwara, Ricardo Toshio
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil/Food and Drug Administration, Bethesda. USA
Food and Drug Administration, Bethesda. USA
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Institute of Molecular Medicine. Center for Biologics Evaluation and Research. Office of Blood Research and Review. Division of Emerging and Transfusion Transmitted Diseases. New Delhi, India
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil
Food and Drug Administration, Bethesda. USA
Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil
Abstract: Live attenuated Leishmania donovani parasites such as LdCen−/− have been shown elicit protective immunity against leishmanial infection in mice and hamster models. Previously, we have reported on the induction of strong immunogenicity in dogs upon vaccination with LdCen−/− including an increase in immunoglobulin isotypes, higher lymphoproliferative response, higher frequencies of activated CD4+ and CD8+ T cells, IFN-γ production by CD8+ T cells, increased secretion of TNF-α and IL-12/IL-23p40 and, finally, decreased secretion of IL-4. To further explore the potential of LdCen−/− parasites as vaccine candidates, we performed a 24-month follow up of LdCen−/− immunized dogs after challenge with virulent Leishmania infantum, aiming determination of parasite burden by qPCR, antibody production (ELISA) and cellular responses (T cell activation and cytokine production) by flow cytometry and sandwich ELISA. Our data demonstrated that vaccination with a single dose of LdCen−/− (without any adjuvant) resulted in the reduction of up to 87.3% of parasite burden after 18 months of virulent challenge. These results are comparable to those obtained with commercially available vaccine in Brazil (Leishmune®). The protection was associated with antibody production and CD4+ and CD8+ proliferative responses, as well as T cell activation and significantly higher production of IFN-γ, IL-12/IL-23p40 and TNF-α, which was comparable to responses induced by immunization with Leishmune®, with significant differences when compared to control animals (Placebo). Moreover, only animals immunized with LdCen−/− expressed lower levels of IL-4 when compared to animals vaccinated either with Leishmune® or PBS. Our results support further studies aiming to demonstrate the potential of genetically modified live attenuated L. donovani vaccine to control L. infantum transmission in endemic areas for CVL.
Keywords: Vaccine
Leishmaniasis
Visceral leishmaniasis
Canine visceral leishmaniasis
Live attenuated
Vaccines
Leishmania
Issue Date: 2015
Publisher: Elsevier Science
Citation: FIUZA, Jacqueline Araújo et al. Vaccination using live attenuated Leishmania donovani centrin deleted parasites induces protection in dogs against Leishmania infantum. Vaccine. 2015 Jan 3;33(2):280-8.
DOI: 10.1016/j.vaccine.2014.11.039.
ISSN: 0264-410X
Copyright: restricted access
Appears in Collections:MG - IRR - Artigos de Periódicos




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