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Centrin-deficient Leishmania mexicana confers protection against Old World visceral leishmaniasis.
Karmakar, Subir; Volpedo, Greta; Zhang, Wen-Wei; Lypaczewski, Patrick; Ismail, Nevien; Oliveira, Fabiano; Oristian, James; Meneses, Claudio; Gannavaram, Sreenivas; Kamhawi, Shaden; Hamano, Shinjiro; Valenzuela, Jesus G; Matlashewski, Greg; Satoskar, Abhay R; Dey, Ranadhir; Nakhasi, Hira L.
Affiliation
  • Karmakar S; Divsion of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, USA.
  • Volpedo G; Department of Pathology and Microbiology, Ohio State University, Columbus, OH, USA.
  • Zhang WW; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
  • Lypaczewski P; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
  • Ismail N; Divsion of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, USA.
  • Oliveira F; Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, 20852, USA.
  • Oristian J; Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, 20852, USA.
  • Meneses C; Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, 20852, USA.
  • Gannavaram S; Divsion of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, USA.
  • Kamhawi S; Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, 20852, USA. skamhawi@niaid.nih.gov.
  • Hamano S; Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
  • Valenzuela JG; The Joint Usage/Research Center on Tropical Disease, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
  • Matlashewski G; Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, 20852, USA. jvalenzuela@niaid.nih.gov.
  • Satoskar AR; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada. Greg.matlashewski@mcgill.ca.
  • Dey R; Department of Pathology and Microbiology, Ohio State University, Columbus, OH, USA. Abhay.Satoskar@osumc.edu.
  • Nakhasi HL; Divsion of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, USA. Ranadhir.Dey@fda.hhs.gov.
NPJ Vaccines ; 7(1): 157, 2022 Dec 03.
Article in En | MEDLINE | ID: mdl-36463228
ABSTRACT
Leishmaniasis is one of the top neglected tropical diseases with significant morbidity and mortality in low and middle-income countries (LMIC). However, this disease is also spreading in the developed world. Currently, there is a lack of effective strategies to control this disease. Vaccination can be an effective measure to control leishmaniasis and has the potential to achieve disease elimination. Recently, we have generated centrin gene-deleted new world L. mexicana (LmexCen-/-) parasites using CRISPR/Cas9 and showed that they protect mice against a homologous L. mexicana infection that causes cutaneous disease. In this study, we tested whether LmexCen-/- parasites can also protect against visceral leishmaniasis caused by L. donovani in a hamster model. We showed that immunization with LmexCen-/- parasites is safe and does not cause lesions. Furthermore, such immunization conferred protection against visceral leishmaniasis caused by a needle-initiated L. donovani challenge, as indicated by a significant reduction in the parasite burdens in the spleen and liver as well as reduced mortality. Similar control of parasite burden was also observed against a sand fly mediated L. donovani challenge. Importantly, immunization with LmexCen-/- down-regulated the disease promoting cytokines IL-10 and IL-4 and increased pro-inflammatory cytokine IFN-γ resulting in higher IFN-γ/IL-10 and IFN-γ/IL4 ratios compared to non-immunized animals. LmexCen-/- immunization also resulted in long-lasting protection against L. donovani infection. Taken together, our study demonstrates that immunization with LmexCen-/- parasites is safe and efficacious against the Old World visceral leishmaniasis.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Country/Region as subject: Mexico Language: En Journal: NPJ Vaccines Year: 2022 Document type: Article Affiliation country: United States
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Country/Region as subject: Mexico Language: En Journal: NPJ Vaccines Year: 2022 Document type: Article Affiliation country: United States