Circulating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients

Ogata, Alana F.; Cheng, Chi‐An; Desjardins, Michaël; Senussi, Yasmeen; Sherman, Amy C; Powell, Megan; Novack, Lewis A.; Von, Salena S.; Li, Xiaofang; Baden, Lindsey R.; Walt, David R.

doi:10.1093/cid/ciab465

Cited by 180 publications

(212 citation statements)

References 10 publications

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“…According to the calibration curve in Figure 3, this corresponds to a maximum concentration of 14.6 μg/mL. Recently published work by Ogata et al used a Quanterix assay measured spike protein in the blood at concentrations less than 50 pg/mL on a similar timescale [10]. The large discrepancy between our photonic assay and the Ogata work was intriguing and may reflect the early stage of knowledge in this area.…”

Section: Resultsmentioning

confidence: 75%

“…While this was conducted at a relatively high concentration, it is important to know then what sort of concentrations of spike protein exist in the blood of vaccinated subjects and for how long. A recent study determined that SARS-CoV-2 spike protein exists in the blood after vaccination [10]. While this represents a useful first step, additional verification of these data is required, along with the development of a platform that can determine this on a broader scale.…”

Section: Introductionmentioning

confidence: 99%

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Monitoring Serum Spike Protein with Disposable Photonic Biosensors Following SARS-CoV-2 Vaccination

Cognetti

Miller

2021

Sensors

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While mRNA vaccines have been well-studied in vitro and in animals prior to their use in the human population during the Covid-19 pandemic, their exact mechanisms of inducing immunity are still being elucidated. The large-scale collection of data necessary to fully understand these mechanisms, and their variability across heterogeneous populations, requires rapid diagnostic tests that accurately measure the various biomarkers involved in the immune response following vaccination. Recently, our lab developed a novel “Disposable Photonics” platform for rapid, label-free, scalable diagnostics that utilizes photonic ring resonator sensor chips combined with plastic micropillar cards able to provide passive microfluidic flow. Here, we demonstrate the utility of this system in confirming the presence of SARS-CoV-2 spike protein in the serum of recently vaccinated subjects, as well as tracking a post-vaccination rise in anti-SARS-CoV-2 antibodies. A maximum concentration in SARS-CoV-2 spike protein was detected one day after vaccination and was reduced below detectable levels within 10 days. This highlights the applicability of our rapid photonic sensor platform for acquiring the data necessary to understand vaccine mechanisms on a large scale, as well as individual patient responses to SARS-CoV-2 mRNA vaccines.

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Section: Resultsmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Monitoring Serum Spike Protein with Disposable Photonic Biosensors Following SARS-CoV-2 Vaccination

Cognetti

Miller

2021

Sensors

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“…23 The fact that COVID-19 vaccination may induce measurable amount of circulating spike protein, thus playing a possible role in the pathogenesis of VITT, is supported by data published by Ogata and colleagues. 24 Another possible interpretation has been provided by Huynh and colleagues. 25 Briefly, it was first found that the binding of anti-PF4 antibodies in the sera of VITT patients involved eight surface amino acids of PF4, all located within the heparin binding site of the protein, but was different from the antigenic moiety recognized by the anti-PF4 antibodies developing in patients with HITT.…”

Section: Pathogenesis Of Vittmentioning

confidence: 87%

Cerebral Venous Thrombosis Developing after COVID-19 Vaccination: VITT, VATT, TTS, and More

Lippi

Favaloro

2021

Semin Thromb Hemost

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Despite the huge efforts globally underway for preventing or limiting the spread of severe acute respiratory coronavirus disease 2 (SARS-CoV-2), the coronavirus disease 2019 (COVID-19) pandemic outbreak appears still virtually unstoppable. As for many other infectious diseases, COVID-19 vaccination has now become crucial for limiting viral spread, especially for averting hospitalizations, need for intensive care, and fatal outcome. Nonetheless, as for other vaccines, COVID-19 vaccination is not completely free from side effects. Among the adverse events that have been reported after receiving COVID-19 vaccination, special emphasis has been given to an unexpected number of thrombocytopenic episodes with or without thrombotic complications, especially in recipients of adenovirus-based COVID-19 vaccines. Along with a specific clinical presentation, encompassing “atypical” thrombosis (especially cerebral venous [sinus] thrombosis, CVT) more prevalent in young female subjects, this new syndrome called vaccine-induced thrombocytopenia and thrombosis (VITT) is characterized by, and thereby diagnosed for, the presence of three paradigmatic laboratory abnormalities, i.e., low platelet count (<150 × 109/L), elevated plasma D-dimer levels (>0.5 mg/L), accompanied by a positive test for anti-PF4 (platelet factor 4) antibodies assayed with ELISA (enzyme-linked immunosorbent assay) techniques. Timely identification of these important abnormalities by both clinicians and laboratory professional is essential for early diagnosis and management of VITT, since the outcome of this condition may be fatal in half or even more of effected patients with severe disease. Therefore, this narrative review aims to review here the epidemiology, pathogenesis, clinical, and laboratory characteristics of VITT and other COVID-19 vaccine-associated thrombocytopenias.

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“…These studies highlight CoV-2-S as a potent culprit that could possibly induce systemic inflammation; however, the underlying molecular mechanism is not fully understood. CoV-2-S has two subunits, with its S1 subunit (CoV-2-S1) being able to be shed into blood stream (Ogata et al, 2021), Importantly, in COVID-19 cases, the serum levels of CoV-2-S1 shows higher positive correlation with clinical severity than CoV-2 nucleocapsid protein (Ogata et al, 2020). Here, our data show that CoV-2-S1 interacts with the extracellular LRR domain of TLR4 and activates NF-kB, suggesting that soluble CoV-2-S1 shed by CoV-2 or infected host cells is a TLR4-recognizable alarmin.…”

Section: Discussionmentioning

confidence: 99%

Selectively expressing SARS-CoV-2 Spike protein S1 subunit in cardiomyocytes induces cardiac hypertrophy in mice

et al. 2021

Preprint

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Cardiac injury is common in hospitalized COVID-19 patients and portends poorer prognosis and higher mortality. To better understand how SARS-CoV-2 (CoV-2) damages the heart, it is critical to elucidate the biology of CoV-2 encoded proteins, each of which may play multiple pathological roles. For example, CoV-2 Spike glycoprotein (CoV-2-S) not only engages ACE2 to mediate virus infection, but also directly impairs endothelial function and can trigger innate immune responses in cultured murine macrophages. Here we tested the hypothesis that CoV-2-S damages the heart by activating cardiomyocyte (CM) innate immune responses. HCoV-NL63 is another human coronavirus with a Spike protein (NL63-S) that also engages ACE2 for virus entry but is known to only cause moderate respiratory symptoms. We found that CoV-2-S and not NL63-S interacted with Toll-like receptor 4 (TLR4), a crucial pattern recognition receptor that responsible for detecting pathogen and initiating innate immune responses. Our data show that the S1 subunit of CoV-2-S (CoV-2-S1) interacts with the extracellular leucine rich repeats-containing domain of TLR4 and activates NF-kB. To investigate the possible pathological role of CoV-2-S1 in the heart, we generated a construct that expresses membrane-localized CoV-2-S1 (S1-TM). AAV9-mediated, selective expression of the S1-TM in CMs caused heart dysfunction, induced hypertrophic remodeling, and elicited cardiac inflammation. Since CoV-2-S does not interact with murine ACE2, our study presents a novel ACE2-independent pathological role of CoV-2-S, and suggests that the circulating CoV-2-S1 is a TLR4-recognizable alarmin that may harm the CMs by triggering their innate immune responses.

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Circulating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients

Cited by 180 publications

References 10 publications

Monitoring Serum Spike Protein with Disposable Photonic Biosensors Following SARS-CoV-2 Vaccination

Monitoring Serum Spike Protein with Disposable Photonic Biosensors Following SARS-CoV-2 Vaccination

Cerebral Venous Thrombosis Developing after COVID-19 Vaccination: VITT, VATT, TTS, and More

Selectively expressing SARS-CoV-2 Spike protein S1 subunit in cardiomyocytes induces cardiac hypertrophy in mice

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