SARS-CoV-2 antibody responses in patients with acute leukaemia

O’Nions, Jenny; Muir, Luke; Zheng, Jiexin; Rees-Spear, Chloe; Rosa, Annachiara; Roustan, Chloë; Earl, Christopher; Cherepanov, Peter; Gupta, Rajeev; Khwaja, Asim; Jolly, Clare; McCoy, Laura E

doi:10.1038/s41375-020-01103-2

Cited by 27 publications

(38 citation statements)

References 10 publications

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“…The differences in resilience to Spike mutations seen in the neutralizing sera from these two infection scenarios is plausibly due to greater polyclonality arising from greater antigenic stimulation during severe illness. To assess the serological profiles of these two cohorts, we compared the 50% inhibitory dilution (ID50) values across 192 samples and measured the binding titers by semi-quantitative ELISA for 199 samples as previously described (Ng et al, 2020;O'Nions et al, 2020). There is a significantly higher median IgG binding titer of 46.5 μg/ml following severe illness versus 3.9 μg/ml following mild/asymptomatic disease (Fig3A,FigS3).…”

Section: Greater Levels Of Spike-reactive Antibodies In Sera After Sementioning

confidence: 95%

“…As described previously (O'Nions et al, 2020) nine columns of a half-well 96-well MaxiSorp plate were coated with purified SARS-CoV-2 Spike S1 protein in PBS (3 µg/ml per well in 25 µL) and the remaining three columns were coated with 25 µL goat anti-human F(ab)'2 diluted 1:1000 in PBS to generate the internal standard curve. After incubation at 4°C overnight, the ELISA plate was blocked for 1 hour in assay buffer (PBS, 5% milk, 0 .…”

Section: Semi-quantitative Elisamentioning

confidence: 99%

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The impact of Spike mutations on SARS-CoV-2 neutralization

Rees-Spear

Muir

Griffith

et al. 2021

Preprint

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Multiple SARS-CoV-2 vaccines have shown protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, Spike. Antibodies from SARS-CoV-2 infection neutralize the virus by focused targeting of Spike and there is limited serum cross-neutralization of the closely-related SARS-CoV. As new SARS-CoV-2 variants are rapidly emerging, exemplified by the B.1.1.7, 501Y.V2 and P.1 lineages, it is critical to understand if antibody responses induced by infection with the original SARS-CoV-2 virus or the current vaccines will remain effective against virus variants. In this study we evaluate neutralization of a series of mutated Spike pseudotypes including a B.1.1.7 Spike pseudotype. The analyses of a panel of Spike-specific monoclonal antibodies revealed that the neutralizing activity of some antibodies was dramatically reduced by Spike mutations. In contrast, polyclonal antibodies in the serum of patients infected in early 2020 remained active against most mutated Spike pseudotypes. The majority of serum samples were equally able to neutralize the B.1.1.7 Spike pseudotype, however potency was reduced in a small number of samples (3 of 36) by 5–10-fold. This work highlights that changes in the SARS-CoV-2 Spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their impact on vaccine efficacy.

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Section: Greater Levels Of Spike-reactive Antibodies In Sera After Sementioning

confidence: 95%

Section: Semi-quantitative Elisamentioning

confidence: 99%

The impact of Spike mutations on SARS-CoV-2 neutralization

Rees-Spear

Muir

Griffith

et al. 2021

Preprint

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“…In acute leukaemia, antibodies against the external spike glycoprotein and internal nucleocapsid were detected in seven (88%) of eight patients. 5 Besides a lower rate of antibody production, the humoral response in patients with haematological conditions is also slower than in the general population. SARS-CoV-2-specific cellular immunity in this group still needs to be characterised.…”

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confidence: 99%

COVID-19 vaccines for patients with haematological conditions

Sun

Pleyer

Wiestner

2021

The Lancet Haematology

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“…As validated and described previously, 22 , 24 , 30 9 columns of a half-well 96-well MaxiSorp plate were coated with purified SARS-CoV-2 spike S1 or N protein in phosphate-buffered saline (PBS) (3 μg/ml per well in 25 μl) and the remaining 3 columns were coated with 25 μl goat antihuman F(ab)’2 diluted 1:1000 in PBS to generate the internal standard curve. After incubation at 4 °C overnight, the ELISA plate was blocked for 1 hour in assay buffer (PBS, 5% milk, 0.05% Tween 20).…”

Section: Methodsmentioning

confidence: 99%

“…HIV-1 particles pseudotyped with SARS-CoV-2 spike (Wuhan-Hu-1) were produced in a T75 flask seeded the day before with 3 million HEK293T cells in 10 ml complete Dulbecco's modified Eagle's medium (Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 100 IU/ml penicillin, and 100 μg/ml streptomycin). Cells were transfected using 60 μg of PEI-Max (Polysciences, Inc., Warrington, PA) with a mixture of the following 3 plasmids: 9.1 μg HIV-1 luciferase reporter vector, 30 9.1 μg HIV p8.91 packaging construct, and 1.4 μg WT SARS-CoV-2 spike expression vector. 30 Supernatants containing pseudotyped virions were harvested 48 hours after transfection, filtered through a 0.45-μm filter, and stored at −80 °C.…”

Section: Methodsmentioning

confidence: 99%

Neutralizing Antibody Responses After SARS-CoV-2 Infection in End-Stage Kidney Disease and Protection Against Reinfection

Muir

Jaffer

Rees-Spear

et al. 2021

Kidney International Reports

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Patients with end-stage kidney disease (ESKD) represent a vulnerable group with multiple risk factors that are associated with poor outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite established susceptibility to infectious complications and the importance of humoral immunity in protection against SARS-CoV-2, few studies have investigated the humoral immune response to SARS-CoV-2 within this population. Here, we evaluate the seroprevalence of SARS-CoV-2 in patients awaiting renal transplantation and determine whether seroconverted patients with ESKD have durable and functional neutralizing activity against SARS-CoV-2. Serum samples were obtained from 164 patients with ESKD by August 2020. Humoral immune responses were evaluated by SARS-CoV-2 spike S1 subunit and nucleoprotein semiquantitative enzyme-linked immunosorbent assay (ELISA) and SARS-CoV-2 spike pseudotype neutralization assay. All patients with ESKD with reverse-transcriptase polymerase chain reaction (RT-PCR)–confirmed infection (n = 17) except for 1 individual seroconverted against SARS-CoV-2. Overall seroprevalence (anti-S1 and/or anti-N IgG) was 36% and was higher in patients on hemodialysis (44.2%). A total of 35.6% of individuals who seroconverted were asymptomatic. Seroconversion in the absence of a neutralizing antibody (nAb) titer was observed in 12 patients, all of whom were asymptomatic. Repeat measurements at a median of 93 days from baseline sampling revealed that most individuals retained detectable responses although a significant drop in S1, N and nAb titers was observed. Patients with ESKD, including those who develop asymptomatic disease, routinely seroconvert and produce detectable nAb titers against SARS-CoV-2. Although IgG levels wane over time, the neutralizing antibodies remain detectable in most patients, suggesting some level of protection is likely maintained, particularly in those who originally develop stronger responses.

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SARS-CoV-2 antibody responses in patients with acute leukaemia

Cited by 27 publications

References 10 publications

The impact of Spike mutations on SARS-CoV-2 neutralization

The impact of Spike mutations on SARS-CoV-2 neutralization

COVID-19 vaccines for patients with haematological conditions

Neutralizing Antibody Responses After SARS-CoV-2 Infection in End-Stage Kidney Disease and Protection Against Reinfection

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