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

Title

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

Creator

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

Publisher

Nature Communications

Date

2020
2020-07-10

Description

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.

Subject

expression; cells; growth; immunity; immunization; protection; immunogenicity; balb/c mice; centrin deleted parasites; cutaneous leishmaniasis

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Format

journalArticle

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Issue

1

Volume

11

ISSN

2041-1723

NEOMED College

NEOMED College of Medicine

NEOMED Department

NEOMED Student Publications

Update Year & Number

August 2020 List

Citation

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, “A second generation leishmanization vaccine with a markerless attenuated leishmania major strain using CRISPR gene editing,” NEOMED Bibliography Database, accessed May 17, 2021, https://neomed.omeka.net/items/show/11209.

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