Establishment, optimisation and quantitation of a bioluminescent murine infection model of visceral leishmaniasis for systematic vaccine screening

Han Boon Ong; Simon Clare; Adam Jonathan Roberts; Mary Edythe Wilson; Gavin James Wright

doi:10.1038/s41598-020-61662-3

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Establishment, optimisation and quantitation of a bioluminescent murine infection model of visceral leishmaniasis for systematic vaccine screening

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Establishment, optimisation and quantitation of a bioluminescent murine infection model of visceral leishmaniasis for systematic vaccine screening

Han Boon Ong, Simon Clare, Adam Jonathan Roberts, Mary Edythe Wilson and Gavin James Wright

Scientific reports, Vol.10(1), pp.4689-4689

03/13/2020

DOI: 10.1038/s41598-020-61662-3

PMCID: PMC7070049

PMID: 32170135

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Abstract

Visceral leishmaniasis is an infectious parasitic disease caused by the protozoan parasites Leishmania donovani and Leishmania infantum. The drugs currently used to treat visceral leishmaniasis suffer from toxicity and the emergence of parasite resistance, and so a better solution would be the development of an effective subunit vaccine; however, no approved vaccine currently exists. The comparative testing of a large number of vaccine candidates requires a quantitative and reproducible experimental murine infection model, but the parameters that influence infection pathology have not been systematically determined. To address this, we have established an infection model using a transgenic luciferase-expressing L. donovani parasite and longitudinally quantified the infections using in vivo bioluminescent imaging within individual mice. We examined the effects of varying the infection route, the site of adjuvant formulation administration, and standardised the parasite preparation and dose. We observed that the increase in parasite load within the liver during the first few weeks of infection was directly proportional to the parasite number in the initial inoculum. Finally, we show that immunity can be induced in pre-exposed animals that have resolved an initial infection. This murine infection model provides a platform for systematic subunit vaccine testing against visceral leishmaniasis.

Leishmania donovani - immunology

Leishmaniasis Vaccines - immunology

Leishmaniasis, Visceral - prevention & control

Mice, Transgenic

Leishmaniasis Vaccines - administration & dosage

Leishmaniasis, Visceral - immunology

Leishmaniasis, Visceral - pathology

Disease Progression

Mice, Knockout

Animals

Luminescent Proteins - genetics

Leishmaniasis, Visceral - parasitology

Mice

Disease Models, Animal

Luminescent Proteins - metabolism

Details

Title: Subtitle: Establishment, optimisation and quantitation of a bioluminescent murine infection model of visceral leishmaniasis for systematic vaccine screening
Creators: Han Boon Ong - Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Cambridge, UK
Simon Clare - Pathogen Laboratory Support, Wellcome Sanger Institute, Cambridge, UK
Adam Jonathan Roberts - Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Cambridge, UK
Mary Edythe Wilson - Departments of Microbiology and Immunology and Internal Medicine, University of Iowa, and the Iowa City Veterans' Affairs Medical Center, Iowa City, USA
Gavin James Wright - Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Cambridge, UK. gw2@sanger.ac.uk
Resource Type: Journal article
Publication Details: Scientific reports, Vol.10(1), pp.4689-4689
DOI: 10.1038/s41598-020-61662-3
PMID: 32170135
PMCID: PMC7070049
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: R01 AI045540 / NIAID NIH HHS Wellcome Trust R01 AI076233 / NIAID NIH HHS I01 BX001983 / BLRD VA I01 BX000536 / BLRD VA
Language: English
Date published: 03/13/2020
Academic Unit: Microbiology and Immunology; Infectious Diseases; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9984066334002771

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