The world is adopting new vaccination strategies to SARS-CoV-2. The ability of a vaccine to provide immunity can be impacted negatively by mutations in the circulating virus or by non-neutralizing cross-reactive from previous coronavirus infections. It is important to monitor immune response and identify cross-reactivity for antigen mutations and common cold coronavirus strains. To study antibody-antigen interactions in a high throughput and label-free manner we use Arrayed Imaging Reflectometry (AIR). AIR provides information about protein binding for an array with a single CCD image by measuring the change in reflectivity of a silicon/silicon dioxide/protein surface (AIR chip). In this talk we discuss our study in which we use a 37-plex AIR array including Influenza and Coronavirus antigens to study changes in the human immune response to vaccination against SARS-CoV-2. Structural changes to viral surface antigens in Coronaviruses and Influenza viruses can change the immune response to those viruses. This talk will discuss the effect of amino acid mutations in SARS-CoV-2 (SARS2) and related coronaviruses, and structural differences in Influenza virus antigens in terms of their presentation: either recombinantly expressed protein or whole virus particles. We hypothesized that the previously mentioned structural differences would lead to changes in amount of antibody binding and cross-reactivity. We have found that in response to SARS2 vaccination, human subjects have significant increases in antibodies against common cold coronavirus 229E, and that those antibodies strongly correlate with increases in antibodies against SARS2 surface antigen proteins. We also found that increase in 229E antibody binding was more strongly correlated with the S2 subunit of the spike protein of SARS2 than with the S1 subunit. We have also found that there is significantly more antibody binding to the S1 D614G mutant protein than to the wild-type protein, though the antibody binding against the two proteins is strongly correlated. In the future, this technology can help understand antibody response as well as antigen cross-reactivity in response to vaccination and infection.
Beyond the optical and analytical performance of the sensor itself, the development of an optical detection tool in response to a pressing research or diagnostic need requires consideration of a host of additional factors. This talk will provide an overview of two photonic sensor systems developed for profiling the human immune response to COVID-19 infection and/or vaccination. One, focused on the design goal of high multiplexing (many targets per sensor), was built on the Arrayed Imaging Reflectometry (AIR) platform. AIR is a free-space optics technique that relies on the creation and target molecule binding-induced disruption of an antireflective coating on the surface of a silicon chip. The second method, focused on low cost and high speed, uses a small (1 x 4 mm) ring resonator photonic chip embedded in a plastic card able to provide passive transport of human samples. This “disposable photonics” platform is able to detect and quantify anti-COVID antibodies in a human sample in a minute, making it attractive for high-throughput testing applications.
Detection of antibodies to upper respiratory pathogens is critical to surveillance, assessment of the immune status of individuals, vaccine development, and basic biology. The urgent need for antibody detection tools has proven particularly acute in the COVID-19 era. Array-based tools are desirable as methods for assessing broader patterns of antigen-specific responses, as well as providing information on SARS-CoV-2 immunity in the context of pre-existing immunity to other viruses. Also, methods that rapidly and quantitatively detect antibody responses to SARS-CoV-2 antigens using small (fingerstick) quantities of blood are essential for monitoring immunity at a global scale. This talk will describe the development of two optical sensor platforms (Arrayed Imaging Reflectometry, and an integrated photonics platform fabricated at AIM Photonics) for quantifying antibodies to SARS-CoV-2 and other upper respiratory pathogens, and oriented towards the needs of multiplex detection and speed.
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