Existing methods to measure influenza vaccine immunogenicity prohibit detailed analysis of epitope determinants recognized by immunoglobulins. We developed influenza hemagglutinin (HA) whole-protein and peptide microarrays and validated that the arrays allow detection of specific antibody reactivity across a broad dynamic range using commercially available antibodies targeted to linear and conformational HA epitopes. In a cohort of 76 young and elderly subjects administered with the 2007/2008 trivalent influenza vaccine, we observed reactivity to influenza whole-protein and peptide array features that correlated significantly with age and post-vaccine titer as assessed through a standard microneutralization assay. One reactive peptide correlated positively with age and negatively with seasonal H1N1 neutralization titer, implicating reactivity to this epitope in age-related defects in response to H1N1 influenza. We also generated models based on age and pre-vaccine peptide reactivity that predicted vaccine-induced neutralization of seasonal H1N1 and H3N2 influenza strains with a high level of accuracy. Our methods provide powerful tools for rapid and accurate measurement of broad antibody-based immune responses to influenza, and may be useful in measuring response to other vaccines and infectious agents.
- Copyright © 2013 by The American Association of Immunologists, Inc.