Towards a predictive understanding of influenza immunity through experimental data integration, iterative model development, and rigorous assessment of model quality

Active Cooperative Agreement Awarded Last action

Award ID
U01AI187062
Recipient
Awarding agency
Obligated
$2,493,234

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 38% complete
Place of performance
La Jolla, CA 92037, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Our central hypothesis is that computational models can accurately predict influenza vaccine breadth and durability based on underlying immunological factors, including an assessment of innate responses triggered by the vaccine, antigen-specific b cells and t cells, the immune exposure history of the host, and genetic factors intrinsic to the host. We propose to capture these variables and their relationship to vaccine outcomes from public datasets and newly generated experimental data. We will build computational models with complementary approaches that use these data to predict vaccine outcomes, and we will host an annual prediction contest that is open to the public to evaluate the predictive performance of these models on unseen data. Our aims are to: 1) capture existing influenza vaccine data and generate new experimental data that connect immunological variables with vaccine breadth and durability. We will: 1.1) collect and standardize data from existing studies that profile the breadth and/or durability of influenza vaccine responses using any of the key immune variables we will assess (genetic factors or innate, b cell, or t cell immunity). This will result in a comprehensive training set for our computational models. 1.2) generate new experimental datasets that measure all of these variables, along with vaccine breadth and durability, to create an independent testing set for our annual competition. 2) generate computational models predicting the breadth and durability of vaccine responses and the cascade of immune events leading up to IT. We will: 2.1) adapt and refine computational models developed by our center investigators to predict vaccine breadth, durability, and key immune events connected to these vaccine outcomes. 2.2) implement models published in the literature to serve as a comparison. 2.3) combine the best- performing models to develop an integrated understanding of influenza vaccine responses. 3) rigorously evaluate model prediction performance on unseen data in an open competition. We will 3.1) perform an annual competition using data from aim 1.2) that was held back from the public to evaluate model performance. 3.2) engage the broader scientific community to participate in the predictive modeling competition and thereby maximize the diversity of independently assessed computational modeling approaches. Overall, this open, transparent, and quantitative process to build and evaluate computational models of influenza vaccination-induced immunity will test our central hypothesis and quantify how well computational models predict vaccine breadth and durability.

Transactions

Action Obligated Date
Amendment $1,246,617
Original award $1,246,617

Subawards

Subrecipient Amount Awarded
University Of Louisville Dr. Watson is a leader in the field of immunogenomics. In collaboration with Co-I Smith, Dr. Watson’s lab has been a driving force in the development of… $37,457
Cleveland Clinic Lerner College Of Medicine Of Case Western Reserve University This proposal is in response to RFA-AI-23-056, which calls for the development of computational models of influenza immunity. Our goal is to answer two key… $152,757
University Of California, San Diego Dr. Grant’s major role in this project is the active engagement and mentoring of up to 45 UC San Diego graduate students per year in the proposed modeling… $37,816
Yale Univ The proposed work at Yale includes the following components: 1. Carry out the analysis of BCR sequencing data. 2. Develop models for predicting influenza… $119,174
University Of Louisville Dr. Watson is a leader in the field of immunogenomics. In collaboration with Co-I Smith, Dr. Watson’s lab has been a driving force in the development… $35,212
University Of California, San Diego Barry Grant has a long history of doing bioinformatics and computational biology research, including molecular modeling and mathematical analysis tightly linked… $35,550
Yale Univ The proposed work at Yale includes the following components: 1. Carry out the analysis of BCR sequencing data. 2. Develop models for predicting influenza… $112,033
Cleveland Clinic Lerner College Of Medicine Of Case Western Reserve University This proposal is in response to RFA-AI-23-056, which calls for the development of computational models of influenza immunity. Our goal is to answer two key… $294,582

Quick answers

Who received award U01AI187062?

U01AI187062 was awarded to La Jolla Institute For Immunology by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on December 19, 2024.

How much is award U01AI187062 worth?

$2,493,234 has been obligated on U01AI187062.

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