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<a href="http://doi.org/10.1038/s41467-020-17154-z" target="_blank" rel="noreferrer noopener">http://doi.org/10.1038/s41467-020-17154-z</a>
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1
Volume
11
ISSN
2041-1723
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Update Year & Number
August 2020 List
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NEOMED College of Medicine
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Title
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A second generation leishmanization vaccine with a markerless attenuated leishmania major strain using CRISPR gene editing
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Nature Communications
Date
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2020
2020-07-10
Subject
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expression; cells; growth; immunity; immunization; protection; immunogenicity; balb/c mice; centrin deleted parasites; cutaneous leishmaniasis
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Zhang W; Karmakar S; Gannavaram S; Dey R; Lypaczewski P; Ismail N; Siddiqui A; Simonyan V; Oliveira F; Coutinho-Abreu I; DeSouza-Vieira T; Meneses C; Oristian J; Serafim TD; Musa Abu; Nakamura R; Saljoughian N; Volpedo G; Satoskar M; Satoskar S; Dagur PK; McCoy JP; Kamhawi S; Valenzuela JG; Hamano S; Satoskar AR; Matlashewski G; Nakhasi HL
Description
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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. Here, the authors engineer an attenuated knock-out Leishmania (LmCen(-/-)) vaccine that is safe in immunocompromised mice and induces an immune response and protection similar to leishmanization with wild-type Leishmania. Since LmCen(-/-) is antibiotic resistant marker free, it is a candidate for clinical development.
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<a href="http://doi.org/10.1038/s41467-020-17154-z" target="_blank" rel="noreferrer noopener">10.1038/s41467-020-17154-z</a>
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journalArticle
2020
August 2020 List
balb/c mice
Cells
centrin deleted parasites
Coutinho-Abreu I
cutaneous leishmaniasis
Dagur PK
DeSouza-Vieira T
Dey R
expression
Gannavaram S
growth
Hamano S
Immunity
Immunization
immunogenicity
Ismail N
journalArticle
Kamhawi S
Karmakar S
Lypaczewski P
Matlashewski G
McCoy JP
Meneses C
Musa Abu
Nakamura R
Nakhasi HL
Nature communications
NEOMED College of Medicine Student
NEOMED Student Publications
Oliveira F
Oristian J
protection
Saljoughian N
Satoskar AR
Satoskar M
Satoskar S
Serafim TD
Siddiqui A
Simonyan V
Valenzuela JG
Volpedo G
Zhang W