Abstract
Introduction: Recently, volumetric absorptive microsampling (VAMS) has been used for accurate sampling of a fixed peripheral blood volume (10 µL) on a volumetric swab, and long-term sample storage. The mPlex-Flu assay is a novel, high-throughput assay that simultaneously measures the concentration of antibodies against the hemagglutinin (HA) proteins from multiple influenza virus strains with ≤5 µL of serum. Here we describe combining these two methods to measure multidimensional anti-influenza IgG activity in whole blood samples collected by a finger stick and VAMS, with correction for serum volume based on simultaneous hemoglobin measurement. Methods: We compared capillary blood samples obtained from a finger stick using a VAMS device with serum samples collected by traditional phlebotomy from 20 subjects, with the influenza antibody profiles measured by the mPlex-Flu assay. Results: We found that results with the two sampling methods were highly correlated within subjects and across all influenza strains (mean R 2 = 0.9470). Adjustment for serum volume, based on hemaglobin measurement, was used to estimate serum volume of samples and improved the accuracy. IgG measurements were stable over 3 weeks when VAMS samples were stored at room temperature or transported using a variety of shipping methods. Additionally, when volunteers performed finger-stick VAMS at-home by themselves, the comparison results of anti-HA antibody concentrations were highly consistent with sampling performed by study personnel on-site (R 2 = 0.9496). Conclusions: This novel approach can provide a simple, accurate, and low-cost means for monitoring the IgG anti-influenza HA antibody responses in large population studies and clinical trials.
Highlights
Volumetric absorptive microsampling (VAMS) has been used for accurate sampling of a fixed peripheral blood volume (10 μL) on a volumetric swab, and long-term sample storage
We show that the combination of volumetric absorptive microsampling (VAMS) with the mPlex-Flu assay could be a powerful tool for large sample size analysis of multidimensional influenza antibody-mediated immunity for use in influenza vaccine and population immunity studies
In order to compare the variability of mPlex-Flu results between capillary blood VAMS versus venous serum sampling, we measured anti-influenza IgG concentrations using the mPlex-Flu assay on simultaneous VAMS finger stick and serum from venipuncture samples (n = 20 subjects)
Summary
Volumetric absorptive microsampling (VAMS) has been used for accurate sampling of a fixed peripheral blood volume (10 μL) on a volumetric swab, and long-term sample storage. Conclusions: This novel approach can provide a simple, accurate, and low-cost means for monitoring the IgG anti-influenza HA antibody responses in large population studies and clinical trials. Both seasonal and emerging influenza virus infection are among the largest reoccurring global public health threats [1], and vaccination is the major method of prevention [2]. A major translational barrier is obtaining serum samples to measure antibody-mediated influenza immunity, which is resource-intensive, time-consuming, and expensive [5] This limits our ability to conduct large-scale influenza vaccine clinical trials, measure population immunity, and assess the mismatch between circulating influenza strains and the seasonal influenza vaccine in real time. Solving this translational barrier would greatly improve our ability to conduct high-quality clinical trials of influenza vaccines, perform large-scale assessments of population immunity to influenza, and greatly decrease the resource intensity of clinical and translational influenza research
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