Label-free, arrayed sensing of immune response to influenza antigens

Mace, Charles R.; Topham, David J.; Mosmann, Tim R.; Quataert, Sally A.; Treanor, John J.; Miller, Benjamin L.

doi:10.1016/j.talanta.2010.11.002

Cited by 22 publications

(20 citation statements)

References 32 publications

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“…Spatially separated probe spots of approximately 100 μm in diameter can be easily resolved, and the technique is therefore useful for multiplexed detection. 29,30 …”

Section: Introductionmentioning

confidence: 99%

Validation of Arrayed Imaging Reflectometry Biosensor Response for Protein–Antibody Interactions: Cross-Correlation of Theory, Experiment, and Complementary Techniques

et al. 2011

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One of the critical steps in the development of an analytical technique is to confirm that its experimental response correlates with predictions derived from the theoretical framework on which it is based. This validates the technique quantitatively, and, in the case of a biosensor, facilitates a correlation of the sensor’s output signal to the concentration of the analyte being tested. Herein we report studies demonstrating that the quantitative response of Arrayed Imaging Reflectometry (AIR), a highly sensitive label-free biosensing method, is a predictable function of probe and analyte properties. We first incorporated a standard one-site Langmuir binding model describing probe-analyte interactions at the surface into the theoretical model for thickness-dependent reflectance in AIR. This established a hypothetical correlation between analyte concentration and the AIR response. Spectroscopic ellipsometry, surface plasmon resonance (SPR) and AIR were then used to validate this model for two biomedically important proteins, fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF). While our studies demonstrated that the 1:1 one-site Langmuir model accurately described the observed response of macro spot AIR arrays, either a two-site Langmuir model or a Sips isotherm better described the behavior of AIR microarrays. These studies confirmed the quantitative performance of AIR across a range of probe-analyte affinities. Furthermore, the methodology developed here can be extended to other label-free biosensing platforms, thus facilitating a more accurate and quantitative interpretation of the sensor response.

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“…Spatially separated probe spots of approximately 100 μm in diameter can be easily resolved, and the technique is therefore useful for multiplexed detection. 29,30 …”

Section: Introductionmentioning

confidence: 99%

Validation of Arrayed Imaging Reflectometry Biosensor Response for Protein–Antibody Interactions: Cross-Correlation of Theory, Experiment, and Complementary Techniques

et al. 2011

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“…To this end, we have developed influenza whole-protein and peptide antigen microarray platforms for the determination of antibody reactivity to conformational and linear epitopes of influenza hemagglutinin (HA). Other groups have reported array-based systems to measure the reactivity of a variety of HA-binding antibodies, including arrays generated with random peptides that can be used to measure the antibody response to influenza vaccination [11], [12], [13]. These studies demonstrate the potential value of an array-based approach.…”

Section: Introductionmentioning

confidence: 89%

Characterization of Influenza Vaccine Immunogenicity Using Influenza Antigen Microarrays

et al. 2013

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BackgroundExisting methods to measure influenza vaccine immunogenicity prohibit detailed analysis of epitope determinants recognized by immunoglobulins. The development of highly multiplex proteomics platforms capable of capturing a high level of antibody binding information will enable researchers and clinicians to generate rapid and meaningful readouts of influenza-specific antibody reactivity.MethodsWe 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. We derived serum from blood draws taken from 76 young and elderly subjects immediately before and 28±7 days post-vaccination with the 2008/2009 trivalent influenza vaccine and determined the antibody reactivity of these sera to influenza array antigens.ResultsUsing linear regression and correcting for multiple hypothesis testing by the Benjamini and Hochberg method of permutations over 1000 resamplings, we identified antibody reactivity to influenza whole-protein and peptide array features that correlated significantly with age, H1N1, and B-strain post-vaccine titer as assessed through a standard microneutralization assay (p<0.05, q <0.2). Notably, we identified several peptide epitopes that were inversely correlated with regard to age and seasonal H1N1 and B-strain neutralization titer (p<0.05, q <0.2), implicating reactivity to these epitopes in age-related defects in response to H1N1 influenza. We also employed multivariate linear regression with cross-validation to build 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 (84.7% and 74.0%, respectively).ConclusionOur 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.

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“…6 The technique has also been validated via comparisons to reference methods including surface plasmon resonance (SPR) and spectroscopic ellipsometry. 7 With regard to influenza-targeted applications, we have demonstrated that multiplex hemagglutinin arrays have utility for rapidly assessing human serum samples for the presence of anti-influenza antibodies in a vaccine trial, 8 and provide a simple method for multiplex serology on avian surveillance samples. 9 Here, we provide a preliminary description of an AIR array intended to simplify the task of classifying newly observed strains of influenza, by enabling patterns of reactivity with the chip to be compared with those generated by known strains of the virus.…”

Section: Bound Probementioning

confidence: 99%

A label-free optical biosensor for serotyping "unknown" influenza viruses

et al. 2016

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The ability to accurately classify influenza viruses is critical to understanding patterns of infection, vaccine efficacy, and to the process of developing new vaccines. Unfortunately, this task is hampered both by the virus' ability to undergo antigenic drift and shift (rendering it a "previously unknown" strain), and by technological limitations. In an effort to overcome these challenges, we have developed a label-free human monoclonal antibody array for flu serology, using a pattern recognition approach to assign virus serotype. The array is built on the Arrayed Imaging Reflectometry (AIR) platform. AIR relies on the creation of a near-perfect antireflective condition on the surface of a silicon chip. When this antireflective condition is perturbed because of binding to an antibody spot (or other immobilized probe molecule), binding may be sensitively and quantitatively detected as an increase in reflected light. We describe fabrication and characterization of the array, and preliminary testing with isolated influenza hemagglutinin. We anticipate that this approach may be extended to other viruses by expansion of the array.

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Label-free, arrayed sensing of immune response to influenza antigens

Cited by 22 publications

References 32 publications

Validation of Arrayed Imaging Reflectometry Biosensor Response for Protein–Antibody Interactions: Cross-Correlation of Theory, Experiment, and Complementary Techniques

Validation of Arrayed Imaging Reflectometry Biosensor Response for Protein–Antibody Interactions: Cross-Correlation of Theory, Experiment, and Complementary Techniques

Characterization of Influenza Vaccine Immunogenicity Using Influenza Antigen Microarrays

A label-free optical biosensor for serotyping "unknown" influenza viruses

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