Characterization of a new Leishmania major strain for use in a controlled human infection model

Helen Ashwin; Jovana Sadlova; Barbora  Vojtkova; Tomas  Becvar; Patrick  Lypaczewski; Eli  Schwartz; Elizabeth  Greensted; Katrien Van Bocxlaer; Marion  Pasin; Kai S.  Lipinski; Vivak Parkash; Greg  Matlashewski; Alison M.  Layton; Charles John Nash Lacey; Charles L.  Jaffe; Petr Volf; Paul Kaye

doi:10.1038/s41467-020-20569-3

Characterization of a new Leishmania major strain for use in a controlled human infection model

Helen Ashwin, Jovana Sadlova, Barbora Vojtkova, Tomas Becvar, Patrick Lypaczewski, Eli Schwartz, Elizabeth Greensted, Katrien Van Bocxlaer, Marion Pasin, Kai S. Lipinski, Vivak Parkash, Greg Matlashewski, Alison M. Layton, Charles John Nash Lacey, Charles L. Jaffe, Petr Volf, Paul Kaye

Research output: Contribution to journal › Article › peer-review

Abstract

Leishmaniasis is widely regarded as a vaccine-preventable disease, but the costs required to reach pivotal Phase 3 studies and uncertainty about which candidate vaccines should be progressed into human studies significantly limits progress in vaccine development for this neglected tropical disease. Controlled human infection models (CHIMs) provide a pathway for accelerating vaccine development and to more fully understand disease pathogenesis and correlates of protection. Here, we describe the isolation, characterization and GMP manufacture of a new clinical strain of Leishmania major. Two fresh strains of L. major from Israel were initially compared by genome sequencing, in vivo infectivity and drug sensitivity in mice, and development and transmission competence in sand flies, allowing one to be selected for GMP production. This study addresses a major roadblock in the development of vaccines for leishmaniasis, providing a key resource for CHIM studies of sand fly transmitted cutaneous leishmaniasis.

Original language	English
Article number	215
Pages (from-to)	215
Number of pages	11
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20569-3
Publication status	Published - 11 Jan 2021

Bibliographical note

Keywords

Animals
Disease Models, Animal
Humans
Insect Vectors/parasitology
Israel
Leishmania major/genetics
Leishmaniasis, Cutaneous/parasitology
Mice, Inbred BALB C
Parasites/genetics
Phylogeny
Psychodidae/parasitology
Whole Genome Sequencing
Mice

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10.1038/s41467-020-20569-3

Characterization of a new Leishmania major strain for use in a controlled human infection model
© The Author(s) 2021
Final published version, 3.31 MBLicence: CC BY

Paul Kaye, PhD FRCPath FMedSci
- paul.kayeyork.acuk
- The Hull York Medical School - Professor
Person: Academic

Cite this

Ashwin, H., Sadlova, J., Vojtkova, B., Becvar, T., Lypaczewski, P., Schwartz, E., Greensted, E., Van Bocxlaer, K., Pasin, M., Lipinski, K. S., Parkash, V., Matlashewski, G., Layton, A. M., Lacey, C. J. N., Jaffe, C. L., Volf, P., & Kaye, P. (2021). Characterization of a new Leishmania major strain for use in a controlled human infection model. Nature Communications, 12(1), 215. Article 215. https://doi.org/10.1038/s41467-020-20569-3

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abstract = "Leishmaniasis is widely regarded as a vaccine-preventable disease, but the costs required to reach pivotal Phase 3 studies and uncertainty about which candidate vaccines should be progressed into human studies significantly limits progress in vaccine development for this neglected tropical disease. Controlled human infection models (CHIMs) provide a pathway for accelerating vaccine development and to more fully understand disease pathogenesis and correlates of protection. Here, we describe the isolation, characterization and GMP manufacture of a new clinical strain of Leishmania major. Two fresh strains of L. major from Israel were initially compared by genome sequencing, in vivo infectivity and drug sensitivity in mice, and development and transmission competence in sand flies, allowing one to be selected for GMP production. This study addresses a major roadblock in the development of vaccines for leishmaniasis, providing a key resource for CHIM studies of sand fly transmitted cutaneous leishmaniasis.",

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author = "Helen Ashwin and Jovana Sadlova and Barbora Vojtkova and Tomas Becvar and Patrick Lypaczewski and Eli Schwartz and Elizabeth Greensted and {Van Bocxlaer}, Katrien and Marion Pasin and Lipinski, {Kai S.} and Vivak Parkash and Greg Matlashewski and Layton, {Alison M.} and Lacey, {Charles John Nash} and Jaffe, {Charles L.} and Petr Volf and Paul Kaye",

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Ashwin, H, Sadlova, J, Vojtkova, B, Becvar, T, Lypaczewski, P, Schwartz, E, Greensted, E, Van Bocxlaer, K, Pasin, M, Lipinski, KS, Parkash, V, Matlashewski, G, Layton, AM, Lacey, CJN, Jaffe, CL, Volf, P & Kaye, P 2021, 'Characterization of a new Leishmania major strain for use in a controlled human infection model', Nature Communications, vol. 12, no. 1, 215, pp. 215. https://doi.org/10.1038/s41467-020-20569-3

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AU - Greensted, Elizabeth

AU - Van Bocxlaer, Katrien

AU - Pasin, Marion

AU - Lipinski, Kai S.

AU - Parkash, Vivak

AU - Matlashewski, Greg

AU - Layton, Alison M.

AU - Lacey, Charles John Nash

AU - Jaffe, Charles L.

AU - Volf, Petr

AU - Kaye, Paul

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N2 - Leishmaniasis is widely regarded as a vaccine-preventable disease, but the costs required to reach pivotal Phase 3 studies and uncertainty about which candidate vaccines should be progressed into human studies significantly limits progress in vaccine development for this neglected tropical disease. Controlled human infection models (CHIMs) provide a pathway for accelerating vaccine development and to more fully understand disease pathogenesis and correlates of protection. Here, we describe the isolation, characterization and GMP manufacture of a new clinical strain of Leishmania major. Two fresh strains of L. major from Israel were initially compared by genome sequencing, in vivo infectivity and drug sensitivity in mice, and development and transmission competence in sand flies, allowing one to be selected for GMP production. This study addresses a major roadblock in the development of vaccines for leishmaniasis, providing a key resource for CHIM studies of sand fly transmitted cutaneous leishmaniasis.

AB - Leishmaniasis is widely regarded as a vaccine-preventable disease, but the costs required to reach pivotal Phase 3 studies and uncertainty about which candidate vaccines should be progressed into human studies significantly limits progress in vaccine development for this neglected tropical disease. Controlled human infection models (CHIMs) provide a pathway for accelerating vaccine development and to more fully understand disease pathogenesis and correlates of protection. Here, we describe the isolation, characterization and GMP manufacture of a new clinical strain of Leishmania major. Two fresh strains of L. major from Israel were initially compared by genome sequencing, in vivo infectivity and drug sensitivity in mice, and development and transmission competence in sand flies, allowing one to be selected for GMP production. This study addresses a major roadblock in the development of vaccines for leishmaniasis, providing a key resource for CHIM studies of sand fly transmitted cutaneous leishmaniasis.

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KW - Disease Models, Animal

KW - Humans

KW - Insect Vectors/parasitology

KW - Israel

KW - Leishmania major/genetics

KW - Leishmaniasis, Cutaneous/parasitology

KW - Mice, Inbred BALB C

KW - Parasites/genetics

KW - Phylogeny

KW - Psychodidae/parasitology

KW - Whole Genome Sequencing

KW - Mice

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DO - 10.1038/s41467-020-20569-3

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SN - 2041-1723

VL - 12

SP - 215

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 215

ER -

Characterization of a new Leishmania major strain for use in a controlled human infection model

Abstract

Bibliographical note

Keywords

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Profiles

Paul Kaye, PhD FRCPath FMedSci

Cite this