# Development of a live attenuated vaccine for visceral leishmaniasis

> **NIH NIH R03** · OHIO STATE UNIVERSITY · 2020 · $78,000

## Abstract

Abstract
Infections caused by the protozoan parasite Leishmania include cutaneous (CL), mucosal (ML), and visceral
leishmaniasis (VL). The WHO classifies leishmaniasis as a neglected tropical disease with over 12 million
current infections globally, and approximately 2 million new cases annually. Patients who recover from
leishmaniasis develop protective immunity against reinfection, which altogether indicates that a vaccine is
feasible. In the past, leishmanization, a process in which deliberate infections with a low dose of Leishmania
major, etiologic agent of zoonotic cutaneous leishmaniasis (ZCL) causes a controlled skin lesion and provides
> 90% protection against reinfection, was a common practice in ZCL-endemic regions. Under the current
regulatory environment such practice is not acceptable due to possibility of complications including non-healing
lesions. However, these studies suggest that live-attenuated parasites which don not cause a disease could be
an effective vaccine for leishmaniasis. Genetically attenuated L. infantum and L. donovani including LdCen-/-
have shown promise as a vaccine in animal models. However, using live-attenuated L. donovani as a vaccine
in humans could raise safety concerns due to visceralizing potential of this Leishmania species. Attenuated
dermatotrophic Leishmania that cross-protects against VL could be a safer vaccine against Leishmania
because adverse events (e.g. development of a lesion as vaccination site) will be easy to monitor and can be
treated using approved non-pharmacological interventions such as topical thermotherapy. Several clinical and
preclinical animal studies have shown that an infection with dermatotrophic Leishmania such as L. major and
L. tropica confers cross-protection against VL caused by L. donovani or L. infantum. Using CRISPR-Cas
technology, we have generated antibiotic selection marker free centrin gene deficient L. major (LmCen-/-).
Whole genome sequencing of LmCen-/- passed through mice multiple times has confirmed stable deletion of
centrin gene without other mutations in the parasite genome. Our preliminary findings show that LmCen-/- are
highly attenuated and fail to cause disease in immunocompromised animals. We have also found that
immunization with LmCen-/- parasites induces disease protective Th1 response in hamsters and protects them
against sand fly transmitted VL caused by L. donovani. Similarly, LmCen-/- immunization also protects against
CL caused by L. major. These findings indicate that LmCen-/- is a promising vaccine for leishmaniasis. Our
industry partner Gennova Biopharma has already established LmCen-/- production under cGMP conditions at
their US-FDA approved facility. In this project, we propose to (Aim 1) perform phenotypic, genetic and
biochemical characterization of GMP-LmCen-/-parasites and (Aim 2) determine whether GMP-LmCen-/- induce
biomarkers of protection in peripheral blood mononuclear cells (PBMCs) from the patients with active VL,
asymptomati...

## Key facts

- **NIH application ID:** 9725441
- **Project number:** 1R03AI144253-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Abhay R Satoskar
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $78,000
- **Award type:** 1
- **Project period:** 2020-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9725441

## Citation

> US National Institutes of Health, RePORTER application 9725441, Development of a live attenuated vaccine for visceral leishmaniasis (1R03AI144253-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9725441. Licensed CC0.

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