Immunization with centrin-Deficient Leishmania braziliensis Does Not Protect against Homologous Challenge.

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.

Citation

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, Camila I de Oliveira. Immunization with centrin-Deficient Leishmania braziliensis Does Not Protect against Homologous Challenge. Vaccines. 2024 Mar 15;12(3)

PMID: 38543944

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