# Collective Responses to Malaria Vaccination

> **NIH NIH U01** · SEATTLE CHILDREN'S HOSPITAL · 2022 · $700,000

## Abstract

SUMMARY
The overall project goal is to identify key characteristics of immune responses to vaccination with attenuated
Plasmodium falciparum sporozoites (aPfSPZs) which results in sterilizing immunity. We hypothesize that this
immunity is due to cellular and humoral responses to specific to Pf antigens (Ags) that are presented during
the liver stage (LS) of infection. We propose a detailed longitudinal analysis of innate and adaptive immune
responses using cutting-edge immunological analyses, associated informatics, and systems immunology. We
will identify aSPZ vaccine-induced cellular and humoral responses that correlate with protection in malaria
naïve and malaria experienced subjects. Complementary orthogonal analytical tools and approaches will
identify relevant immune cell subsets, Ag receptor (AR) repertoires, lineages, and specificities to protective
Ags. The functional characteristics of the immune cells and products, including antibodies, that correlate with
protection will be identified and validated. This will be accomplished by: Aim 1: Identifying aSPZ vaccine
induced cellular and humoral responses that are associated with protection. Unbiased and Ag specific cellular
profiling will characterize the kinetics of protection associated responses to vaccination and CHMI. Follow-on
analyses will profile identified Ag-specific adaptive and innate cellular responses by mass cytometry (CyTOF),
multiplexed pMHC/Ag multimer staining, and multi-omic single cell sequencing to determine protection-
associated gene and protein expression signatures and functional antibody responses, which will be extended
in later aims. Aim 2: Identify protection associated T and B cell Ag receptor (AR) repertoires at key times after
vaccinations and CHMI. Natively paired and single ARs chains from T and B cells will be sequenced to
determine repertoire attributes and identify vaccine induced Pf Ag specific ARs. Cellular transcriptomic profiles
and Ag specificities will be linked by joint single cell and TCR/BCR sequence analyses. Novel AR-Ag and
antibody specificities will be identified by yeast display methods. This aim will identify T and B cell ARs and
antibody Ag specificities that are correlated with protection. Aim 3: Identifying functional characteristics of
cellular and antibody responses that confer protection. Sorted reactive T cells will be assayed by Ag-specific
CyTOF-based intracellular cytokine staining (ICS), activation-induce marker (AIM), and single-cell sequence
based multi-omics analyses. The biophysical and functional analyses of monoclonal antibodies will be used to
assess B cell roles in protection. The comprehensive project data will undergo integrated multi-factorial
bioinformatic analysis, curation and sharing using established platforms. Overall, this project will identify key
characteristics of the intricate immune responses to the complex antigenic composition of aSPZ Pf vaccination
and the effector processes that correlate with protect...

## Key facts

- **NIH application ID:** 10343347
- **Project number:** 1U01AI165455-01
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** KENNETH D STUART
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $700,000
- **Award type:** 1
- **Project period:** 2022-02-09 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10343347

## Citation

> US National Institutes of Health, RePORTER application 10343347, Collective Responses to Malaria Vaccination (1U01AI165455-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10343347. Licensed CC0.

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