# A Cytomegalovirus-based Vaccine Targeting the Pre-erythrocytic Stage of Malaria

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $747,848

## Abstract

SUMMARY
The development of a sterilizing vaccine against malaria remains one of the highest priorities for global health
research. While experimental vaccines targeting the malaria parasite prior to entering the blood stage have
shown great promise, it has so far not been possible to elicit the longterm immunity required to maintain
protection over time. We propose to apply a fundamentally new vaccine tool to malaria vaccine research:
persistent effector memory T cell-eliciting vaccines based on cytomegalovirus (CMV). By taking advantage of
the natural ability of CMV to elicit and maintain high frequency, non-exhausted, life-long cellular immunity we
demonstrated that CMV-based vaccines protect against highly virulent pathogens such as simian immune-
deficiency virus and mycobacterium tuberculosis. Our work has renewed hope for AIDS eradication and we are
now in clinical development of CMV/HIV vaccines. In preliminary work we now also show that CMV-based
malaria vaccines containing a limited set of malaria antigens reduce the parasite burden prior to blood stage
development. The central goal of this proposal is to further improve this protection in order to generate
sterilizing immunity. We will apply the unique immunological characteristics of CMV-based vaccines by
designing CMV-vaccines that recruit different types of cytotoxic T cells to eliminate the parasite liver stage.
Specifically, we will address the role of conventional, MHC-I restricted CD8+ T cells versus unconventional
MHC-II and MHC-E-restricted CD8+ T cells in protection. We will additionally broaden the spectrum of parasite
antigens by including a new set of vaccine targets for the pre-erythrocytic stage of malaria. These new vaccine
targets were selected based on systematic evaluation of T cell immunity in humans and validation in murine
malaria models. Finally we will extend the immune responses and protective effects elicited by heterologous
prime/boost immunization by boosting with CMV-vectors eliciting MHC-I restricted CD8+ T cells recognizing
both immunodominant and subdominant epitopes. We anticipate that this project will validate CMV as new
method to vaccinate against malaria.

## Key facts

- **NIH application ID:** 9982274
- **Project number:** 5R01AI123182-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Klaus J Fruh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $747,848
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982274

## Citation

> US National Institutes of Health, RePORTER application 9982274, A Cytomegalovirus-based Vaccine Targeting the Pre-erythrocytic Stage of Malaria (5R01AI123182-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982274. Licensed CC0.

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