Production of leishmanin skin test antigen from Leishmania donovani for future reintroduction in the field

Ranadhir Dey; Jalal Alshaweesh; Kamaleshwar P Singh; Patrick Lypaczewski; Subir Karmakar; Laura Klenow; Kayla Paulini; Swarnendu Kaviraj; Shaden Kamhawi; Jesus G Valenzuela; Sanjay Singh; Shinjiro Hamano; Abhay R Satoskar; Sreenivas Gannavaram; Hira L Nakhasi; Greg Matlashewski

doi:10.1038/s41467-023-42732-2

Production of leishmanin skin test antigen from Leishmania donovani for future reintroduction in the field

Nat Commun. 2023 Nov 2;14(1):7028. doi: 10.1038/s41467-023-42732-2.

Authors

Ranadhir Dey^#¹, Jalal Alshaweesh^#^{2

3}, Kamaleshwar P Singh^#⁴, Patrick Lypaczewski⁵, Subir Karmakar⁴, Laura Klenow¹, Kayla Paulini⁵, Swarnendu Kaviraj⁴, Shaden Kamhawi⁶, Jesus G Valenzuela⁶, Sanjay Singh⁷, Shinjiro Hamano^{8

9}, Abhay R Satoskar¹⁰, Sreenivas Gannavaram¹¹, Hira L Nakhasi¹², Greg Matlashewski¹³

Affiliations

¹ Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, USA.
² Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
³ The Joint Usage/Research Center on Tropical Disease, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
⁴ Gennova Biopharmaceuticals, Hinjawadi Phase II, Pune, Maharashtra, India.
⁵ Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
⁶ Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland, 20852, USA.
⁷ Gennova Biopharmaceuticals, Hinjawadi Phase II, Pune, Maharashtra, India. Sanjay.Singh@gennova.co.in.
⁸ Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan. shinjiro@nagasaki-u.ac.jp.
⁹ The Joint Usage/Research Center on Tropical Disease, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan. shinjiro@nagasaki-u.ac.jp.
¹⁰ Department of Pathology and Microbiology, Ohio State University, Columbus, OH, USA. Abhay.Satoskar@osumc.edu.
¹¹ Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, USA. Sreenivas.Gannavaram@fda.hhs.gov.
¹² Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, USA. hira.nakhasi@fda.hhs.gov.
¹³ Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada. greg.matlashewski@mcgill.ca.

^# Contributed equally.

Abstract

The leishmanin skin test was used for almost a century to detect exposure and immunity to Leishmania, the causative agent of leishmaniasis, a major neglected tropical disease. Due to a lack of antigen used for the intradermal injection, the leishmanin skin test is no longer available. As leishmaniasis control programs are advancing and new vaccines are entering clinical trials, it is essential to re-introduce the leishmanin skin test. Here we establish a Leishmania donovani strain and describe the production, under Good Laboratory Practice conditions, of leishmanin soluble antigen used to induce the leishmanin skin test in animal models of infection and vaccination. Using a mouse model of cutaneous leishmaniasis and a hamster model of visceral leishmaniasis, soluble antigen induces a leishmanin skin test response following infection and vaccination with live attenuated Leishmania major (LmCen^-/-). Both the CD4⁺ and CD8⁺ T-cells are necessary for the leishmanin skin test response. This study demonstrates the feasibility of large-scale production of leishmanin antigen addressing a major bottleneck for performing the leishmanin skin test in future surveillance and vaccine clinical trials.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Protozoan
CD8-Positive T-Lymphocytes
Leishmania donovani*
Leishmaniasis, Cutaneous* / prevention & control
Skin Tests

Substances

leishmanin
Antigens, Protozoan