Systems biological assessment of vaccination-induced protective immunity in african children

Active Cooperative Agreement Awarded Last action

Award ID
U01AI165527
Recipient
Awarding agency
Obligated
$6,903,990

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 95% complete
Place of performance
Palo Alto, CA 94304, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
The most advanced malaria vaccine candidate, RTS, S, provides only partial efficacy against clinical malaria episodes when given to young children. Furthermore, efficacy wanes within 12-18 months post vaccination, with many children having low magnitude and/or rapidly waning immune responses, and booster doses are only partially efficacious. The immunologic mechanisms underlying sub-optimal and waning immune responses and vaccine efficacy remain unclear. We propose to utilize a multi-omics, systems biology approach to define baseline, and vaccine-induced signatures that predict immunogenicity and protection, following RTS, S vaccination of young children in malawi. This project will take advantage of an extraordinary opportunity to comprehensively study baseline and vaccine-induced immune responses to RTS, S in young children through a collaboration with the malawi international centers of excellence in malaria research (ICEMR). The malawi ICEMR is studying the effectiveness of RTS, S to prevent malaria infection and transmission in a longitudinal cohort of children as part of a world health organization-sponsored implementation study. By leveraging our well-characterized cohort, detailed immunological characterization of host responses, and state-of-the-art computational models of immunity, we will in aim 1 perform a systems analysis of baseline signatures that predict immunogenicity and protection from primary vaccination against PF. We will use a multi-omics approach, using bulk RNA-SEQ, metabolomics of serum, cytometry by time of flight with epigenetic profiling (EPITOF), and single cell epigenetic profiling to profile baseline signatures prior to primary RTS, S vaccination in 300 malawian children. Our goal will be to perform an integrated analysis of these orthogonal datasets to define a baseline signature that can be used to predict the immunogenicity and efficacy of RTS, S vaccination. In aim 2, we will perform a systems analysis of vaccine-induced signatures that predict immunogenicity and protection from primary and booster vaccination against PF. We will use a multi-omics approach, using bulk RNA-SEQ, metabolomics of serum, multiplex analysis of serum cytokines and CSP-specific T cell assays, to comprehensively profile vaccine- induced signatures following RTS, S vaccination in malawian children. We will perform an integrated analysis of these datasets to define vaccine-induced signatures that can be used to predict the immunogenicity and efficacy of RTS, S vaccination. The successful completion of these aims will provide deep insight into the molecular mechanisms underlying suboptimal immunity to RTS, S vaccination, and yield biomarkers of vaccine- induced immunity and protection.

Transactions

Action Obligated Date
Amendment $20,983
Amendment $913,011
Amendment $905,972
Amendment $532,012
Amendment $532,012
Amendment $0
Amendment $0
Amendment $0
Amendment $800,000
Amendment $800,000
Amendment $800,000
Amendment $800,000
Original award $800,000
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Subawards

Subrecipient Amount Awarded
Trustees Of Boston University Dr. Valim is one of the multi-Principal Investigators (MPIs) of the proposed work. In the first two years of the funding period, Dr. Valim will be responsible… $253,098
Trustees Of Boston University $212,971
Kamuzu University Of Health Sciences "Two cohorts will be enrolled in the Nyambi Health Center. The first cohort will be comprised of 365 children age-eligible children (5-7 months) to receive… $122,515
Trustees Of Boston University Dr. Valim is one of the multi-Principal Investigators (MPIs) of the proposed work. In the first two years of the funding period, Dr. Valim will be responsible… $147,730
The Macfarlane Burnet Institute For Medical Research And Public Health LTD Dr. Beeson will coordinate and supervise the conduct of all antibody assays in his laboratory. He will supervise the Research Associate who will conduct these… $77,322
Kamuzu University Of Health Sciences "Two cohorts will be enrolled in the Nyambi Health Center. The first cohort will be comprised of 365 children age-eligible children (5-7 months) to receive… $163,231

Quick answers

Who received award U01AI165527?

U01AI165527 was awarded to The Leland Stanford Junior University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on February 1, 2022.

How much is award U01AI165527 worth?

$6,903,990 has been obligated on U01AI165527.

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