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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Modeling and Analysis of Biological Systems Study Section (MABS)
Program Officer
Lane, Mary Chelsea
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Rochester
Internal Medicine/Medicine
School of Medicine & Dentistry
United States
Zip Code
Nogales, Aitor; Piepenbrink, Michael S; Wang, Jiong et al. (2018) A Highly Potent and Broadly Neutralizing H1 Influenza-Specific Human Monoclonal Antibody. Sci Rep 8:4374
Wang, Jiong; Hilchey, Shannon P; DeDiego, Marta et al. (2018) Broad cross-reactive IgG responses elicited by adjuvanted vaccination with recombinant influenza hemagglutinin (rHA) in ferrets and mice. PLoS One 13:e0193680
Huang, Junqiong; Hilchey, Shannon P; Wang, Jiong et al. (2017) IL-15 enhances cross-reactive antibody recall responses to seasonal H3 influenza viruses in vitro. F1000Res 6:2015