A second generation leishmanization vaccine with a markerless attenuated Leishmania major strain using CRISPR gene editing.

Jul 13, 2020

Contributor: Wen-Wei Zhang,Subir Karmakar,Sreenivas Gannavaram,Ranadhir Dey,Patrick Lypaczewski,Nevien Ismail,Abid Siddiqui,Vahan Simonyan,Fabiano Oliveira,Iliano V Coutinho-Abreu,Thiago DeSouza-Vieira,Claudio Meneses,James Oristian,Tiago D Serafim,Abu Musa,Risa Nakamura,Noushin Saljoughian,Greta Volpedo,Monika Satoskar,Sanika Satoskar,Pradeep K Dagur,J Philip McCoy,Shaden Kamhawi,Jesus G Valenzuela,Shinjiro Hamano,Abhay R Satoskar,Greg Matlashewski,Hira L Nakhasi

A second generation leishmanization vaccine with a markerless attenuated Leishmania major strain using CRISPR gene editing.

Leishmaniasis is a neglected tropical disease caused by Leishmania protozoa transmitted by infected sand flies. Vaccination through leishmanization with live Leishmania major has been used successfully but is no longer practiced because it resulted in occasional skin lesions. A second generation leishmanization is described here using a CRISPR genome edited L. major strain (LmCen). Notably, LmCen is a genetically engineered centrin gene knock-out mutant strain that is antibiotic resistant marker free and does not have detectable off-target mutations. Mice immunized with LmCen have no visible lesions following challenge with L. major-infected sand flies, while non-immunized animals develop large and progressive lesions with a 2-log fold higher parasite burden. LmCen immunization results in protection and an immune response comparable to leishmanization. LmCen is safe since it is unable to cause disease in immunocompromised mice, induces robust host protection against vector sand fly challenge and because it is marker free, can be advanced to human vaccine trials.

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About The Expert

Wen-Wei Zhang

Department of Microbiology and Immunology, McGill University, Montreal, QC, H3A 2B4, Canada.

Subir Karmakar

Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, 20993, USA.

Sreenivas Gannavaram

Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, 20993, USA.

Ranadhir Dey

Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, 20993, USA.

Patrick Lypaczewski

Department of Microbiology and Immunology, McGill University, Montreal, QC, H3A 2B4, Canada.

Nevien Ismail

Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, 20993, USA.

Abid Siddiqui

Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, 20993, USA.

Vahan Simonyan

Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, 20993, USA.

Fabiano Oliveira

Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.

Iliano V Coutinho-Abreu

Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.

Thiago DeSouza-Vieira

Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.

Claudio Meneses

Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.

James Oristian

Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.

Tiago D Serafim

Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.

Abu Musa

Department of Parasitology, Institute of Tropical Medicine (NEKKEN), The Joint Usage/Research Center on Tropical Disease, Nagasaki University, Nagasaki, Japan and Nagasaki University Graduate School of Biomedical Sciences Doctoral Leadership Program, Nagasaki, Japan.

Risa Nakamura

Department of Parasitology, Institute of Tropical Medicine (NEKKEN), The Joint Usage/Research Center on Tropical Disease, Nagasaki University, Nagasaki, Japan and Nagasaki University Graduate School of Biomedical Sciences Doctoral Leadership Program, Nagasaki, Japan.

Noushin Saljoughian

Department of Pathology and Microbiology, Ohio State University, Columbus, OH, 43210, USA.

Greta Volpedo

Department of Pathology and Microbiology, Ohio State University, Columbus, OH, 43210, USA.

Monika Satoskar

Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, 20993, USA.

Northeast Ohio Medical University, Rootstown, Ohio, 44272, USA.

Sanika Satoskar

Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, 20993, USA.

Northeast Ohio Medical University, Rootstown, Ohio, 44272, USA.

Pradeep K Dagur

National Institute of Heart, Lung and Blood Institute, NIH, Bethesda, MD, 20852, USA.

J Philip McCoy

National Institute of Heart, Lung and Blood Institute, NIH, Bethesda, MD, 20852, USA.

Shaden Kamhawi

Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.

Jesus G Valenzuela

Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.

Shinjiro Hamano

Department of Parasitology, Institute of Tropical Medicine (NEKKEN), The Joint Usage/Research Center on Tropical Disease, Nagasaki University, Nagasaki, Japan and Nagasaki University Graduate School of Biomedical Sciences Doctoral Leadership Program, Nagasaki, Japan.

Abhay R Satoskar

Department of Pathology and Microbiology, Ohio State University, Columbus, OH, 43210, USA. Abhay.Satoskar@osumc.edu.

Greg Matlashewski

Department of Microbiology and Immunology, McGill University, Montreal, QC, H3A 2B4, Canada. greg.matlashewski@mcgill.ca.

Hira L Nakhasi

Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, 20993, USA. Hira.Nakhasi@fda.hhs.gov.

References

PubMed