Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Enhancing T and B cell responses to Plasmodium infection and vaccination via IL-15

Award Number: R01AI185750
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/20/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2025
AWARD TERMINATION DATE: 05/19/2025

Group Awards By:

View Award Description

Enhancing T and B cell responses to Plasmodium infection and vaccination via IL-15 - PROJECT SUMMARY/ABSTRACT Malaria, which results from infection with Plasmodium parasites, is a significant global health problem with nearly 250 million clinical cases and over 600,000 deaths annually worldwide. With growing anti-malarial drug and insecticide resistance, new therapeutic strategies and highly effective vaccines are urgently needed. Protection against symptomatic disease develops after years of repeated exposures to Plasmodium parasites. However, there is no definitive evidence of long-lived, sterilizing immunity in humans following repeated exposure to Plasmodium parasites, and clinical immunity to malaria rapidly wanes in the absence of re- infection. Similarly, the limited protection offered by the most advanced malaria vaccines lose efficacy quickly in malaria endemic areas. Dysregulated inflammation is thought to contribute to the short-lived response to Plasmodium. The cellular processes impairing the acquisition and maintenance of cellular and humoral immunity to Plasmodium are not known. Therapies that boost the robustness and durability of the immune response could be transformative in vaccine development. This project centers on investigating an IL-15 cytokine-based therapy that enhances the immune response to Plasmodium infection and vaccination. The proposed studies will utilize novel peptide:MHC class II and B cell tetramers in experimental Plasmodium infection and vaccination mouse models. We found that in the context of Plasmodium infection in mice, IL-15 therapy promotes the differentiation of T follicular helper (Tfh) cells, which are critical for promoting long-lived and high-quality antibody responses. In the context of whole sporozoite Plasmodium vaccination, IL- 15 therapy increases the number of liver-resident CD8 T memory (Trm) cells and antibody levels, suggesting that IL-15 could be harnessed as an adjuvant to enhance Plasmodium vaccine immunogenicity. In this proposal, we will define the mechanism by which IL-15 therapy promotes Tfh differentiation as well as germinal center formation and antibody generation in the context of Plasmodium infection using novel conditional knockout mouse models and our novel tetramer reagents (Aim 1). We will also define the impact of IL-15 therapy as a vaccine adjuvant to enhance CD8 T cell responses as well as CD4 T cell and B cell/antibody responses to a whole sporozoite Plasmodium vaccine (Aim 2). These studies will define the mechanistic pathways induced by IL-15 treatment that enhance Plasmodium control to both understand the disease more completely and develop therapies that exploit these pathways. Overall, these studies will deliver foundational knowledge of the naturally-acquired and vaccine-elicited immune response to Plasmodium. This information will be leveraged for the rational design of vaccination strategies to improve anti-Plasmodium immunity.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$105,522 )
2026	2024	HENNEPIN HEALTHCARE RESEARCH INSTITUTE	701 PARK AVE	MINNEAPOLIS	MN	55415	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	1	3/31/2026	TERMINATION	-$105,522
														Subtotal = -$105,522

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	HENNEPIN HEALTHCARE RESEARCH INSTITUTE	701 PARK AVE	MINNEAPOLIS	MN	55415	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	1	5/15/2025	TERMINATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $606,767 )
2024	2024	HENNEPIN HEALTHCARE RESEARCH INSTITUTE	701 PARK AVE	MINNEAPOLIS	MN	55415	HENNEPIN	USA	Allergy and Infectious Diseases Research	001	1	9/3/2024	NEW	$49,935
2024	2024	HENNEPIN HEALTHCARE RESEARCH INSTITUTE	701 PARK AVE	MINNEAPOLIS	MN	55415	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	1	6/20/2024	NEW	$556,832
														Subtotal = $606,767

Grand Total All Awards = $501,245

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Enhancing T and B cell responses to Plasmodium infection and vaccination via IL-15

Award Number: R01AI185750

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/20/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2025

AWARD TERMINATION DATE: 05/19/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer