# Group 1 CD1-restricted human T cells induced by a whole sporozoite-based malaria vaccine

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $283,500

## Abstract

PROJECT SUMMARY:
The group 1 CD1 molecules, CD1a, CD1b, CD1c, as well as CD1e molecules are present in humans but absent
in mice. These are important molecules that have been shown to present antigens containing lipid moieties and
stimulate human T cells in vitro. Therefore, we have created "humanized" mice that not only express human
group 1 CD1 molecules, but also possess functional human T lymphocytes that are developed and differentiated
from human hematopoietic stem cells (HSCs). This was done by first transfecting BRG (BALB/c-Rag2nullIL-
2Rγnull)-derived ES cells with large fragments of human genomic DNA that contain human group 1 CD1 genes
using Bacterial Artificial Chromosome (BAC) technology. After injecting engineered ES cells into C57BL/6
blastocysts, followed by transferring them to a foster C57BL/6 mouse, the human group 1 CD1-transgenic
(hCD1-TG) chimeric mouse was generated. Then, by backcrossing the chimeric mouse, as a founder, onto
NSG (NOD/SCID-Rag2nullIL-2Rγnull) mice for more than 7 generations, hCD1-TG NSG mice were established.
The neonates of the hCD1-TG NSG mice were then transduced with genes that encode human hematopoietic
cytokines, which are necessary to generate the human immune system (HIS) by the adeno-associated virus
(AAV) vector-mediated gene delivery approach. One to two weeks later, the transduced hCD1-TG NSG mice
were sub-lethally irradiated and engrafted with human HSCs. Fourteen weeks later, group 1 CD1-restricted
human T cells were successfully differentiated and developed from HSCs in hCD1-TG NSG mice. We named
such hCD1-TG NSG mice having functional human T cells and other human immune competent cells (B and
NK cells and DCs), hCD1-TG HIS mice. Such mice are an ideal model for the study of malaria, which is still a
cause of one of the most prevalent infectious diseases worldwide. Currently a whole sporozoite-based malaria
vaccine has emerged as one of the leading vaccine candidates. A malaria sporozoite consists of lipids, similar
to other pathogens like Mycobacterium tuberculosis. For example, a crystal structure study revealed that a
malaria sporozoite protein, called UIS3, forms a complex with lipid, phosphatidylethanolamine (PE), which binds
one of the group 1 CD1 molecules. Therefore, our hCD1-TG HIS mice will permit us to investigate the nature
and longevity of the group 1 CD1-resricted human T-cell response induced in hCD1-TG HIS mice by the whole
sporozoite-based malaria vaccine in Aim 1. Here we will employ a cutting-edge analytical framework which
integrates not only surface markers and cytokines/transcription factors, but also T-cell receptor repertoire at
single cell resolution in a heterogeneous population. In Aim 2, we will determine whether group 1 CD1-restricted
human T cells induced by the whole sporozoite-based vaccine contribute to protective anti-malaria immunity in
the hCD1-TG HIS mice. We hope that the proposed studies will address the role of group 1 CD1-restricted T
cells in prote...

## Key facts

- **NIH application ID:** 9958276
- **Project number:** 1R21AI151469-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** MORIYA TSUJI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $283,500
- **Award type:** 1
- **Project period:** 2020-03-10 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9958276

## Citation

> US National Institutes of Health, RePORTER application 9958276, Group 1 CD1-restricted human T cells induced by a whole sporozoite-based malaria vaccine (1R21AI151469-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9958276. Licensed CC0.

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