1. Immunization with centrin-Deficient Leishmania braziliensis Does Not Protect against Homologous Challenge
- Author
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Francys Avendaño-Rangel, Gabriela Agra-Duarte, Pedro B. Borba, Valdomiro Moitinho, Leslye T. Avila, Larissa O. da Silva, Sayonara M. Viana, Rohit Sharma, Sreenivas Gannavaram, Hira L. Nakhasi, and Camila I. de Oliveira
- Subjects
live attenuated vaccine ,immunization ,vaccination ,cutaneous leishmaniasis ,Medicine - 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.
- Published
- 2024
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