# A universal malaria T cell vaccine based on HLA-E presentation

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $752,069

## Abstract

ABSTRACT
Malaria-specific CD8+ T cells have long been known to control the liver stages of malaria. We recently showed
that they can also kill reticulocytes infected with Plasmodium vivax. However, the T cell targeted antigens
presented by major histocompatibility complex (MHC) class I molecules on parasite-infected cells at any stage
are largely unknown; a lack of knowledge that has hampered the development of rationally designed, T cell-
based vaccines for malaria. In preliminary experiments we determined the MHC-I peptidome presented on P.
vivax-infected reticulocytes. This analysis revealed that many MHC-I-bound peptides are derived from
abundant house-keeping proteins such as histones and ribosomal proteins that are highly conserved among
Plasmodium species—targets not represented in current vaccine strategies. This discovery thus creates the
unique opportunity to develop pan-Plasmodium vaccines eliciting T cells to validated targets. Unexpectedly,
several peptides were identified in multiple donors regardless of their MHC-haplotype and our preliminary data
show this is in part due to peptide presentation on MHC-E, a non-polymorphic MHC-Ib molecule. We therefore
hypothesize that MHC-E-restricted CD8+ T cells contribute to T cell-mediated protection against malaria and
that this can be exploited for vaccine design using cytomegalovirus (CMV)-based vectors, the only platform
that can be programmed to elicit MHC-E-restricted CD8+ T cell responses to inserted antigens. This hypothesis
will be tested in three specific aims using the P. cynomolgi non-human primate model of P. vivax with
validation in human P. vivax-infected samples: In Aim 1 we will determine the relative contribution of MHC-E to
presentation of P.vivax peptides to CD8+ T cells and investigate a possible role of MHC-E-targeting in CD8+ T
cell killing of infected reticulocytes (iRetics). In Aim 2 we will characterize the role of individual P. vivax
antigens in MHC-E-restricted CD8+ T cell targeting of iRetics. This will be accomplished by identifying MHC-
E/peptide-specific T cell receptors and examining the ability of TCR-transfected T cells to target iRetics . In
addition, we will similarly characterize MHC-E-restricted CD8+ T cells elicited to selected antigens in rhesus
macaques immunized with genetically modified rhesus cytomegalovirus vectors (RhCMV) that elicit exclusively
MHC-E-restricted CD8+ T cells. In Aim 3, we will compare RhCMV-based P. vivax vaccines eliciting MHC-E or
MHC-Ia-restricted responses to selected, conserved antigens with respect to their ability to protect against P.
cynomolgi challenge in rhesus macaques. Specifically, we will monitor protection against the liver stage,
primary blood stage and relapsing blood stage resulting from dormant liver stages. This collaborative program
brings together diverse expertise and, if successful, will provide a highly innovative approach to malaria
vaccine development that is expected to have a lasting impact on vaccine...

## Key facts

- **NIH application ID:** 10419367
- **Project number:** 1R01AI168092-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Caroline Junqueira
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $752,069
- **Award type:** 1
- **Project period:** 2022-05-20 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10419367

## Citation

> US National Institutes of Health, RePORTER application 10419367, A universal malaria T cell vaccine based on HLA-E presentation (1R01AI168092-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10419367. Licensed CC0.

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