# Inducing durable, protective immune memory against malaria

> **NIH NIH U01** · SEATTLE CHILDREN'S HOSPITAL · 2021 · $802,689

## Abstract

Project Summary
 The goal of generating a licensed vaccine that can provide long-lived immunity against infection with
Plasmodium falciparum, the protozoan parasite that causes the most lethal form of malaria, is yet unrealized.
Currently, the malaria vaccine candidate that has undergone the most extensive clinical testing is RTS,S, a
subunit vaccine based on the circumsporozoite protein (CSP), expressed on the surface of the infectious
sporozoite stage of the parasite. Yet, as seen with many other vaccine strategies, protection induced by
vaccination with RTS,S is not only suboptimal, it also wanes rapidly and there is negligible prevention of clinical
disease measured four years after immunization. A critical bottleneck for the generation of a protective malaria
vaccine is therefore understanding how to generate long-lived, Plasmodium-specific immune memory, especially
in people in malaria endemic countries. One promising approach is to gain greater insight into the immune
response to whole attenuated sporozoite vaccines, which can lead to the development of high levels
(>60%) of sterile immunity in malaria naïve subjects when tested by challenge using controlled human
malaria infection (CHMI) and has shown for the first time protection against infection in malaria-exposed
subjects in Africa. In this application, we will focus on three major questions that are critical to enhancing our
understanding of how immunity can be maintained after whole sporozoite vaccination: 1) how does the innate
immune response after sporozoite vaccination influence the development of long-lived adaptive memory, 2) how
does previous malaria infection alter the generation of sporozoite vaccine-induced memory and 3) how can we
harness recently characterized memory cell signatures in the blood to understand the maintenance of long-lived
immune cells in the tissues after sporozoite vaccination.
 Our team consists of experts in immunology, vaccinology, parasitology and collaborators that conduct
sporozoite vaccine trials, and will pursue a fully integrated approach to address these questions. To answer
these questions, we will use both relevant human samples obtained from malaria-naïve and malaria pre-exposed
subjects who received different modes of whole sporozoite vaccination, as well as murine malaria models, which
allow immune system perturbations and access to target organs. We will combine our unique expertise with
novel tools and techniques to provide key insights into how immunological memory can be maintained after
immunization, which will broadly inform vaccination strategies for malaria, as well as other infectious diseases
for which vaccines are not currently available.

## Key facts

- **NIH application ID:** 10084807
- **Project number:** 5U01AI142001-03
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Stefan HI Kappe
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $802,689
- **Award type:** 5
- **Project period:** 2019-01-16 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084807

## Citation

> US National Institutes of Health, RePORTER application 10084807, Inducing durable, protective immune memory against malaria (5U01AI142001-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10084807. Licensed CC0.

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