| Author | Rangel, Francys Avendaño | |
| Author | Duarte, Gabriela Agra | |
| Author | Borba, Pedro B. | |
| Author | Moitinho, Valdomiro | |
| Author | Avila, Leslye T. | |
| Author | Silva, Larissa O. da | |
| Author | Viana, Sayonara M. | |
| Author | Sharma, Rohit | |
| Author | Gannavaram, Sreenivas | |
| Author | Nakhasi, Hira L. | |
| Author | Oliveira, Camila I. de | |
| Access date | 2024-05-20T18:24:54Z | |
| Available date | 2024-05-20T18:24:54Z | |
| Document date | 2024 | |
| Citation | RANGEL, Francys Avendaño et al. Immunization with centrin-deficient leishmania braziliensis does not protect against homologous challenge. Vaccines, v. 12, n.3, p. 1-15, 2024. | en_US |
| ISSN | 2076-393X | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/64140 | |
| Sponsorship | Ministério da Ciência, Tecnologia e Inovação - Brasil.
Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT-DT).
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB).
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). | en_US |
| Language | eng | en_US |
| Publisher | MDPI | en_US |
| Rights | open access | en_US |
| Subject in Portuguese | Vacina viva atenuada | en_US |
| Subject in Portuguese | Imunização | en_US |
| Subject in Portuguese | Vacinação | en_US |
| Subject in Portuguese | Leishmaniose cutânea | en_US |
| Title | Immunization with centrin-deficient leishmania braziliensis does not protect against homologous challenge | en_US |
| Type | Article | en_US |
| DOI | 10.3390/ vaccines12030310 | |
| Abstract | Immunization with various Leishmania species lacking centrin induces robust immunity against a homologous and heterologous virulent challenge, making centrin mutants a putative candidate for a leishmaniasis vaccine. Centrin is a calcium-binding cytoskeletal protein involved in centrosome duplication in higher eukaryotes and Leishmania spp. lacking centrin are unable to replicate in vivo and are non-pathogenic. We developed a centrin-deficient Leishmania braziliensis (LbCen−/−) cell line and confirmed its impaired survival following phagocytosis by macrophages. Upon experimental inoculation into BALB/c mice, LbCen−/− failed to induce lesions and parasites were rapidly eliminated. The immune response following inoculation with LbCen−/− was characterized by a mixed IFN-γ, IL-4, and IL-10 response and did not confer protection against L. braziliensis infection, distinct from L. major, L. donovani, and L mexicana centrin-deficient mutants. A prime-boost strategy also did not lead to a protective immune response against homologous challenge. On the contrary, immunization with centrin-deficient L. donovani (LdonCen−/−) cross-protected against L. braziliensis challenge, illustrating the ability of LdonCen−/− to induce the Th1-dominant protective immunity needed for leishmaniasis control. In conclusion, while centrin deficiency in L. braziliensis causes attenuation of virulence, and disrupts the ability to cause disease, it fails to stimulate a protective immune response. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | en_US |
| Affilliation | Division of Emerging and Transfusion Transmitted Diseases. CBER, FDA. Silver Spring, MD, USA. | en_US |
| Affilliation | Division of Emerging and Transfusion Transmitted Diseases. CBER, FDA. Silver Spring, MD, USA. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT). Salvador, BA, Brasil. | en_US |
| Subject | Live attenuated vaccine | en_US |
| Subject | Immunization | en_US |
| Subject | Vaccination | en_US |
| Subject | Cutaneous leishmaniasis | en_US |
| DeCS | Vacinas | en_US |
| DeCS | Vacinação | en_US |
| DeCS | Leishmaniose cutânea | en_US |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
