# Resident Memory T cells in Leishmaniasis

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $402,500

## Abstract

The development of effective vaccines for intracellular microbial pathogens, such as mycobacteria,
toxoplasma, plasmodium, and leishmania, remains an elusive goal. Despite substantial efforts to define the
mechanisms required for resistance, develop new adjuvants, and identify protective antigens, the long-lived
cellular immunity that can be generated in response to infection is not always recapitulated by vaccination.
For example, in spite of the strong immunity that develops following an infection with leishmania, efforts to
develop a vaccine for human leishmaniasis have been unsuccessful. Lack of success is due in part to the
limited understanding of the T cells that mediate protection. While we have identified circulating T cell
subsets that contribute to immunity in leishmaniasis (1), these circulating T cells fail to provide the level of
immunity observed in mice that have resolved a primary infection with L. major. Using a combination of skin
grafting and adoptive transfers, however, we found that leishmania-responsive IFN-γ producing CD4+ T
cells resident in the skin are the missing link required for optimal protective immunity (2). We propose to
identify how they are generated and maintained in the skin, determine how they promote immunity, and
target them in a leishmanial vaccine. These studies are important for leishmaniasis, and have broad
implications for vaccine development against other pathogens. In Aim 1 we will define the factors that
regulate the accumulation of CD4+ resident memory T cells in the skin following resolution of a primary
infection. These studies have direct relevance to vaccine development, as they will define what will be
required for generating resident memory T cells. In Aim 2, we focus on the mechanisms by which resident
memory T cells mediate protection. Here we will identify the effector T cells that synergize with resident
memory T cells to mediate protection, and determine if resident memory T cells help to amplify the
generation of T effector cells. Finally, in Aim 3 we will translate this information into an experimental
vaccine. We will create a recombinant vaccinia virus expressing a leishmanial antigen, and assess the
protection induced by this vaccine and qualitatively and quantitatively define the T cells that contribute to
that protection.

## Key facts

- **NIH application ID:** 9916704
- **Project number:** 5R01AI125265-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** PHILLIP SCOTT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,500
- **Award type:** 5
- **Project period:** 2016-05-16 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9916704

## Citation

> US National Institutes of Health, RePORTER application 9916704, Resident Memory T cells in Leishmaniasis (5R01AI125265-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9916704. Licensed CC0.

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