Annual immunization against in?uenza infection is one of the largest coordinated international public health ef- forts. Current in?uenza vaccination strategies elicit protection primarily through the generation of long lasting, type-speci?c, neutralizing anti-HA IgG antibodies. A major reason for the success of the seasonal in?uenza vac- cination is that it induces antibodies that bind to molecularly similar in?uenza subtypes. However, we currently lack both high throughput assays and multidimensional analytic methods to rapidly characterize comprehensive individual and population level IgG mediated immunity to a broad range of in?uenza strains, or to predict popula- tion immunity against new strains. The primary goal of this proposal is to develop an innovative multidimensional assay and quantitative modeling framework to characterize population level immunity to a large number of in- ?uenza strains, and predict responses to new in?uenza vaccines.
In Aim 1, we will use a novel multiplex assay to measure pre-and post- vaccine anti-HA IgG reactivity against 50 in?uenza strains in 150 subjects. We then will test and validate a predictive model for vaccine induced changes in anti-HA IgG levels.
In Aim 2 we will use the data from Aim 1 to estimate changes in population immunity pre- and post-standard seasonal in?uenza vacci- nation. Multidimensional scaling will be used to develop functional immune repertoire cartography, quantitatively modeling both the similarity of subject immune states and a model of vaccine-induced changes in the anti-HA IgG repertoire vector. Successful completion of these Aims will establish a new hybrid experimental-modeling method for predicting in?uenza vaccine responses and estimating population resistance to emerging in?uenza strains.

Public Health Relevance

Immunization against in?uenza results in protective antibodies that bind to the viral surface and prevent infec- tion, including cross-reactive antibodies that bind to other in?uenza strains. We have developed a method for measuring antibody levels against 50 in?uenza strains with a tiny blood drop from a ?nger stick. The goal of this proposal is to use this method, with mathematical modeling to predict in?uenza vaccine responses in individuals and populations. If successful, this work will create a new paradigm for evaluating in?uenza vaccine success in individuals and populations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI138500-02
Application #
9625080
Study Section
Modeling and Analysis of Biological Systems Study Section (MABS)
Program Officer
Lane, Mary Chelsea
Project Start
2018-01-12
Project End
2019-12-31
Budget Start
2019-01-01
Budget End
2019-12-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Rochester
Department
Internal Medicine/Medicine
Type
School of Medicine & Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627