Immunization with <i>centrin</i>-Deficient <i>Leishmania braziliensis</i> Does Not Protect against Homologous Challenge
Immunization with various <i>Leishmania</i> species lacking <i>centrin</i> induces robust immunity against a homologous and heterologous virulent challenge, making <i>centrin</i> mutants a putative candidate for a leishmaniasis vaccine. Centrin is a calcium-bindin...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-03-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/12/3/310 |
| _version_ | 1797239120231137280 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Francys Avendaño-Rangel |
| collection | DOAJ |
| description | Immunization with various <i>Leishmania</i> species lacking <i>centrin</i> induces robust immunity against a homologous and heterologous virulent challenge, making <i>centrin</i> mutants a putative candidate for a leishmaniasis vaccine. Centrin is a calcium-binding cytoskeletal protein involved in centrosome duplication in higher eukaryotes and <i>Leishmania</i> spp. lacking centrin are unable to replicate <i>in vivo</i> and are non-pathogenic. We developed a <i>centrin</i>-deficient <i>Leishmania braziliensis</i> (<i>LbCen<sup>−/−</sup></i>) cell line and confirmed its impaired survival following phagocytosis by macrophages. Upon experimental inoculation into BALB/c mice, <i>LbCen<sup>−/−</sup></i> failed to induce lesions and parasites were rapidly eliminated. The immune response following inoculation with <i>LbCen<sup>−/−</sup></i> was characterized by a mixed IFN-γ, IL-4, and IL-10 response and did not confer protection against <i>L. braziliensis</i> infection, distinct from <i>L. major</i>, <i>L. donovani</i>, and <i>L mexicana</i> centrin-deficient mutants. A prime-boost strategy also did not lead to a protective immune response against homologous challenge. On the contrary, immunization with <i>centrin</i>-deficient <i>L. donovani</i> (<i>LdonCen<sup>−/−</sup></i>) cross-protected against <i>L. braziliensis</i> challenge, illustrating the ability of <i>LdonCen<sup>−/−</sup></i> to induce the Th1-dominant protective immunity needed for leishmaniasis control. In conclusion, while <i>centrin</i> deficiency in <i>L. braziliensis</i> causes attenuation of virulence, and disrupts the ability to cause disease, it fails to stimulate a protective immune response. |
| first_indexed | 2024-04-24T17:46:29Z |
| format | Article |
| id | doaj.art-b4adae6e682d4013afe28c0f38a39e1e |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-24T17:46:29Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-b4adae6e682d4013afe28c0f38a39e1e2024-03-27T14:07:06ZengMDPI AGVaccines2076-393X2024-03-0112331010.3390/vaccines12030310Immunization with <i>centrin</i>-Deficient <i>Leishmania braziliensis</i> Does Not Protect against Homologous ChallengeFrancys Avendaño-Rangel0Gabriela Agra-Duarte1Pedro B. Borba2Valdomiro Moitinho3Leslye T. Avila4Larissa O. da Silva5Sayonara M. Viana6Rohit Sharma7Sreenivas Gannavaram8Hira L. Nakhasi9Camila I. de Oliveira10Instituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, BrazilInstituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, BrazilInstituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, BrazilInstituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, BrazilInstituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, BrazilInstituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, BrazilInstituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, BrazilInstituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, BrazilDivision of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD 20993, USADivision of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD 20993, USAInstituto Gonçalo Moniz, FIOCRUZ, Salvador 40296-710, BA, BrazilImmunization with various <i>Leishmania</i> species lacking <i>centrin</i> induces robust immunity against a homologous and heterologous virulent challenge, making <i>centrin</i> mutants a putative candidate for a leishmaniasis vaccine. Centrin is a calcium-binding cytoskeletal protein involved in centrosome duplication in higher eukaryotes and <i>Leishmania</i> spp. lacking centrin are unable to replicate <i>in vivo</i> and are non-pathogenic. We developed a <i>centrin</i>-deficient <i>Leishmania braziliensis</i> (<i>LbCen<sup>−/−</sup></i>) cell line and confirmed its impaired survival following phagocytosis by macrophages. Upon experimental inoculation into BALB/c mice, <i>LbCen<sup>−/−</sup></i> failed to induce lesions and parasites were rapidly eliminated. The immune response following inoculation with <i>LbCen<sup>−/−</sup></i> was characterized by a mixed IFN-γ, IL-4, and IL-10 response and did not confer protection against <i>L. braziliensis</i> infection, distinct from <i>L. major</i>, <i>L. donovani</i>, and <i>L mexicana</i> centrin-deficient mutants. A prime-boost strategy also did not lead to a protective immune response against homologous challenge. On the contrary, immunization with <i>centrin</i>-deficient <i>L. donovani</i> (<i>LdonCen<sup>−/−</sup></i>) cross-protected against <i>L. braziliensis</i> challenge, illustrating the ability of <i>LdonCen<sup>−/−</sup></i> to induce the Th1-dominant protective immunity needed for leishmaniasis control. In conclusion, while <i>centrin</i> deficiency in <i>L. braziliensis</i> causes attenuation of virulence, and disrupts the ability to cause disease, it fails to stimulate a protective immune response.https://www.mdpi.com/2076-393X/12/3/310live attenuated vaccineimmunizationvaccinationcutaneous leishmaniasis |
| spellingShingle | 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 <i>centrin</i>-Deficient <i>Leishmania braziliensis</i> Does Not Protect against Homologous Challenge Vaccines live attenuated vaccine immunization vaccination cutaneous leishmaniasis |
| title | Immunization with <i>centrin</i>-Deficient <i>Leishmania braziliensis</i> Does Not Protect against Homologous Challenge |
| title_full | Immunization with <i>centrin</i>-Deficient <i>Leishmania braziliensis</i> Does Not Protect against Homologous Challenge |
| title_fullStr | Immunization with <i>centrin</i>-Deficient <i>Leishmania braziliensis</i> Does Not Protect against Homologous Challenge |
| title_full_unstemmed | Immunization with <i>centrin</i>-Deficient <i>Leishmania braziliensis</i> Does Not Protect against Homologous Challenge |
| title_short | Immunization with <i>centrin</i>-Deficient <i>Leishmania braziliensis</i> Does Not Protect against Homologous Challenge |
| title_sort | immunization with i centrin i deficient i leishmania braziliensis i does not protect against homologous challenge |
| topic | live attenuated vaccine immunization vaccination cutaneous leishmaniasis |
| url | https://www.mdpi.com/2076-393X/12/3/310 |
| work_keys_str_mv | AT francysavendanorangel immunizationwithicentrinideficientileishmaniabraziliensisidoesnotprotectagainsthomologouschallenge AT gabrielaagraduarte immunizationwithicentrinideficientileishmaniabraziliensisidoesnotprotectagainsthomologouschallenge AT pedrobborba immunizationwithicentrinideficientileishmaniabraziliensisidoesnotprotectagainsthomologouschallenge AT valdomiromoitinho immunizationwithicentrinideficientileishmaniabraziliensisidoesnotprotectagainsthomologouschallenge AT leslyetavila immunizationwithicentrinideficientileishmaniabraziliensisidoesnotprotectagainsthomologouschallenge AT larissaodasilva immunizationwithicentrinideficientileishmaniabraziliensisidoesnotprotectagainsthomologouschallenge AT sayonaramviana immunizationwithicentrinideficientileishmaniabraziliensisidoesnotprotectagainsthomologouschallenge AT rohitsharma immunizationwithicentrinideficientileishmaniabraziliensisidoesnotprotectagainsthomologouschallenge AT sreenivasgannavaram immunizationwithicentrinideficientileishmaniabraziliensisidoesnotprotectagainsthomologouschallenge AT hiralnakhasi immunizationwithicentrinideficientileishmaniabraziliensisidoesnotprotectagainsthomologouschallenge AT camilaideoliveira immunizationwithicentrinideficientileishmaniabraziliensisidoesnotprotectagainsthomologouschallenge |