A novel highly quantitative and reproducible assay for the detection of anti-SARS-CoV-2 IgG and IgM antibodies

Noda, Kenta; Matsuda, Kouki; Yagishita, Shigehiro; Maeda, Kenji; Akiyama, Yutaro; Terada-Hirashima, Junko; Matsushita, Hiromichi; Iwata, Satoshi; Yamashita, Kazuto; Atarashi, Yusuke; Watanabe, S.; Ide, Nobuyuki; Yoshida, Tomokazu; Ohmagari, Norio; Mitsuya, Hiroaki; Hamada, Akinobu

doi:10.1038/s41598-021-84387-3

Cited by 65 publications

(63 citation statements)

References 40 publications

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“…However, the assumption of the half-lifes in the present work was based on the chronologically linear nature of the reduction observed during the present study period (Figure 3D). Also, the sensitivity and quantitativeness of S1-binding-IgG and -IgM levels determined with using the chemiluminescence enzyme immunoassay (CLEIA) platform (HISCL) 24 were much greater (the dynamic range is 0.1 to 2,000 SU/ml) than that of neutralizing activity, whose dynamic range is 20 to 4,000 . Thus, the time length of S1-binding-IgG becoming under detection levels was calculated to be longer than that of neutralizing activity, although it should be noted that the protective effect of BNT162b2 judged by neutralizing activity is most likely associated with clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

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Correlates of Neutralizing/SARS-CoV-2-S1-binding Antibody Response with Adverse Effects and Immune Kinetics in BNT162b2-Vaccinated Individuals

Maeda

Amano

Uemura³

et al. 2021

Preprint

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Background: While mRNA vaccines against SARS-CoV-2 have been exceedingly effective in preventing symptomatic viral infection, the features of immune response remain to be clarified. Methods: In the present prospective observational study, 225 healthy individuals in Kumamoto General Hospital, Japan, who received two BNT162b2 doses in February 2021, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT50; assessed using infectious virions and live target cells) with SARS-CoV-2-S1-binding-IgG and -IgM levels, adverse effects (AEs), ages, and genders were examined. The average half-life of neutralizing activity and the average time length for the loss of detectable neutralizing activity were determined and the potency of serums against variants of concerns was also determined. Findings: Significant rise in NT50s was seen in serums on day 28 post-1st dose. A moderate inverse correlation was seen between NT50s and ages, but no correlation was seen between NT50s and AEs. NT50s and IgG levels on day 28 post-1st dose and pain scores following the 2nd shot were greater in women than in men. The average half-life of neutralizing activity in the vaccinees was approximately 67.8 days and the average time length for their serums to lose the detectable neutralizing activity was 198.3 days. While serums from elite-responders (NT50s>1,500-fold: the top 4% among all participants' NT50s) potently to moderately blocked the infectivity of variants of concerns, some serums with moderate NT50s failed to block the infectivity of a beta strain. Interpretation: BNT162b2-elicited immune response has no significant association with AEs. BNT162b2-efficacy is likely diminished to under detection limit by 6-7 months post-1st shot. High-level neutralizing antibody-containing serums potently to moderately block the infection of SARS-CoV-2 variants; however, a few moderate-level neutralizing antibody-containing serums failed to do so. If BNT162b2-elicited immunity memory is short, an additional vaccine or other protective measures would be needed.

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Section: Discussionmentioning

confidence: 99%

“…Measurement of 3 anti-SARS-CoV-2 antibody levels (anti-S1-IgG, anti-S1-IgM, and anti-N-IgG) in each participant was performed using the chemiluminescence enzyme immunoassay (CLEIA) platform (HISCL) manufactured by Sysmex Co. (Kobe, Japan) as previously reported 24 .…”

Section: Measurement Of Anti-sars-cov-2 Antibody Titersmentioning

confidence: 99%

Correlates of Neutralizing/SARS-CoV-2-S1-binding Antibody Response with Adverse Effects and Immune Kinetics in BNT162b2-Vaccinated Individuals

Maeda

Amano

Uemura³

et al. 2021

Preprint

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“…Routine tests for the measurement of cellular immunity against SARS-CoV-2 are being developed. [4, 5, 6]…”

Section: Introductionmentioning

confidence: 99%

Monitoring of anti-SARS-CoV-2 IgG antibody immune response in infected and immunised healthcare workers in Hungary: a real-world longitudinal cohort study

Gervain

Szabo

Baki

et al. 2021

Preprint

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Introduction SARS-CoV-2 infections have very different clinical manifestations and anti-SARS-CoV-2 immunisation may also trigger very different levels and length of protection. While (re)infection after previous COVID-19 illness or following vaccination are known, their impact and the optimal timing of any booster vaccination is currently debated. International evidence about potential underlying immune response differences remains limited and is currently not available in Hungary. Methods We prospectively investigated the magnitude of immune responses to infection or immunisation, their over-time changes and the occurrence of new infections through anti-SARS-CoV-2 IgG levels and the association with selected individual and clinical parameters in two voluntary cohorts of healthcare workers at a public teaching hospital in a real-world longitudinal cohort study in Hungary. In the first cohort, the anti-nucleocapsid IgG levels of 42 health care workers (female: 100%) with SARS-CoV-2 infection were followed-up over 8 months between June 2020 and February 2021. Beyond the change in immune response, associations with age, selected existing chronic conditions, blood type and severity of symptoms were investigated. In the immunised cohort, anti-spike-RBD protein IgG levels of 49 health care workers (female: 73%) with no prior COVID-19 infection were monitored up to 4 months following initial immunisation with BNT162b2 vaccine between December 2020 and April 2021. Statistical analyses included median analysis, linear regression, ANCOVA, Kruskal-Wallis test and Skillings-Mack test for block designs as relevant. Results Within the infected cohort, the median time of anti-SARS-CoV-2 IgG level reduction below the positive test cut-off was 6 months. First month IgG levels were on average the highest among those in illness severity category 4, but the difference to less severe categories was not statistically significant. Higher age was associated with higher IgG levels. Within the immunised cohort, the anti-SARS-CoV-2 spike-RBD protein IgG levels increased 25-fold between the first and second immunisations, significantly decreased to 33% of the peak level after 90 days, and had an overall negative tendency with older age and male sex. IgG monitoring revealed 17% (7/42) and 14% (7/49) new infections in the infected and the immunised cohorts, respectively, all symptomless. Discussion Our study is the first to investigate the level, change and associations of anti-SARS-CoV-2 IgG immune response in infected or immunised healthcare workers in Hungary. It provides further evidence about the significantly declining IgG protection through initial infection beyond 6 months. While immunisation with mRNA vaccination shows a similar pattern of reduction in protection, IgG levels remained within the positive range at 4 months. The observed rate of 15% new, asymptomatic infections and their potential broader impacts call for further investigations. Overall, our findings are confirmative of the effectiveness of vaccination to prevent illness, recent considerations for booster vaccination beyond 6 months, and indicate the potential benefit of anti-SARS-CoV-2 IgG monitoring for optimisation.

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“…Partly, these tests have generated unreliable data and some of the available enzyme-linked immunosorbent assays (ELISA) for the measurement of binding antibodies have exhibited limited precision ( 112 , 113 ). A new optimized quantitative test for SARS-CoV-2 spike- and nucleocapsid-binding IgG and IgM antibodies has recently been developed based on chemiluminescence enzyme immunoassay (CLEIA) technology with the goal of being able to determine a threshold for the definition of protective immunity soon ( 114 ).…”

Section: Measuring Humoral and Cellular Responses To Vaccinationmentioning

confidence: 99%

Approach to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis

et al. 2021

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For more than a year now, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been causing the coronavirus disease (COVID-19) pandemic with high mortality and detrimental effects on society, economy, and individual lives. Great hopes are being placed on vaccination as one of the most potent escape strategies from the pandemic and multiple vaccines are already in clinical use. However, there is still a lot of insecurity about the safety and efficacy of vaccines in patients with autoimmune diseases like multiple sclerosis (MS), especially under treatment with immunomodulatory or immunosuppressive drugs. We propose strategic approaches to SARS-CoV-2 vaccination management in MS patients and encourage fellow physicians to measure the immune response in their patients. Notably, both humoral and cellular responses should be considered since the immunological equivalent for protection from SARS-CoV-2 after infection or vaccination still remains undefined and will most likely involve antiviral cellular immunity. It is important to gain insights into the vaccine response of immunocompromised patients in order to be able to deduce sensible strategies for vaccination in the future.

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A novel highly quantitative and reproducible assay for the detection of anti-SARS-CoV-2 IgG and IgM antibodies

Cited by 65 publications

References 40 publications

Correlates of Neutralizing/SARS-CoV-2-S1-binding Antibody Response with Adverse Effects and Immune Kinetics in BNT162b2-Vaccinated Individuals

Correlates of Neutralizing/SARS-CoV-2-S1-binding Antibody Response with Adverse Effects and Immune Kinetics in BNT162b2-Vaccinated Individuals

Monitoring of anti-SARS-CoV-2 IgG antibody immune response in infected and immunised healthcare workers in Hungary: a real-world longitudinal cohort study

Approach to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis

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