# Immune Responses Associated with Malaria Infection and Immune Protection - Project 1

> **NIH NIH U19** · SEATTLE CHILDREN'S HOSPITAL · 2020 · $629,668

## Abstract

Scientific Project 1: Immune Responses to Preerythocytic Malaria
This project will comprehensively define human immune responses during the pre-erythrocytic stage of
Plasmodium falciparum infection and vaccination with attenuated sporozoites which prevents infection and
thus target this stage. It will identify immune signatures during the pre-erythrocytic, immunization and post
vaccination periods in complementary vaccine trials that assess protection by controlled human malaria
infection (CHMI). The primary endpoint is a correlation of vaccine-induced protection from infection, secondary
endpoints are the effects of prior malaria exposure and differences in immunization protocols, vaccines and
CHMI methods. The exploratory endpoints include the identification of signals that implicate immune processes
that contribute to protection. The approach combines formal statistical methods, well-defined endpoints and
system biology analyses. It systematically integrates high-dimensional with diverse immunological analyses to
generate an expansive immunological view to identify and assess signals that are associated with protection. It
aims to: 1. Identify immune responses during the pre-erythrocytic stages of infection. Virtually nothing is
known about this stage the infection in the liver during which there is extensive parasite replication and
synthesis of new antigens. We will identify signals of infection and of immunization with attenuated SPZs
during this stage and compare variations among trials. 2. Determine immune response kinetics over the
immunization period. We will identify the kinetics of innate and adaptive immunological signals during
immunization with attenuated SPZs and identify the development of those that correlate with protection and
how these differ among the trials. We will deduce molecular and cellular features from the signals that correlate
with each variable to provide insight into immune processes that are associated with each endpoint. 3.
Compare responses at and following of malaria challenge infection. We will identify signatures in samples
from vaccinees prior to and following assessment by CHMI of protection from infection. We will compare
immune signatures that are associated with each endpoint. The results from all of the aims will be used to
guide the selection and testing of specific hypotheses about the mechanisms that underlay each of the
endpoints. Overall, the comprehensive and integrated immunological and systems biology analyses will identify
immune signatures during the critical stage of infection by and immune protection against a complex protozoan
pathogen. It will generate and analyze pooled data from multiple complementary vaccine trials in order to
identify correlates of protection from infection, how these are affected by variables among the trials. It will
provide insight into multiple aspects of immune processes that are operative during infection and affected by
vaccination.

## Key facts

- **NIH application ID:** 9954009
- **Project number:** 5U19AI128914-05
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** KENNETH D STUART
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $629,668
- **Award type:** 5
- **Project period:** 2017-07-19 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954009

## Citation

> US National Institutes of Health, RePORTER application 9954009, Immune Responses Associated with Malaria Infection and Immune Protection - Project 1 (5U19AI128914-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9954009. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*