SARS-CoV-2 Antibody Responses Are Correlated to Disease Severity in COVID-19 Convalescent Individuals

Hansen, Cecilie Bo; Jarlhelt, Ida; Pérez‐Alós, Laura; Landsy, Lone Hummelshøj; Loftager, Mette; Rosbjerg, Anne; Helgstrand, Charlotte; Bjelke, Jais Rose; Egebjerg, Thomas; Jardine, Joseph G.; Jørgensen, Charlotte Sværke; Iversen, Kasper; Bayarri‐Olmos, Rafael; Garred, Peter; Skjoedt, Mikkel‐Ole

doi:10.4049/jimmunol.2000898

Cited by 112 publications

(129 citation statements)

References 31 publications

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“…Unless otherwise stated, all incubation steps were performed for 1 h at RT in a shaking platform, and the plates were washed between steps with PBS-T. Plates were developed with TMB One for 7 min for IgG, and 10 min for IgM and IgA, and the reaction was stopped with 0.3 M H2SO4, and the OD measured as described previously. Antibody titers against RBD have previously been reported by our group 19 .…”

Section: Production and Purification Of Recombinant Ace-2 Ectodomain mentioning

confidence: 53%

“…The nucleotide sequence was synthesized by GeneArt (Thermo Fisher Scientific) and subcloned into a pcDNA3.4 expression vector. The production and purification of SARS-CoV-2 protein N, RBD, and trimeric prefusion-stabilized spike protein ectodomain used for immunization 19 . Purified RBD was biotinylated with a biotin ligase kit (Avidity, Colorado, USA) according to the manufacturer's instructions.…”

Section: Production and Purification Of Recombinant Ace-2 Ectodomain mentioning

confidence: 99%

“…Antibodies were captured directly from supernatants. Briefly, 1 four-parameter non-linear curve fitting and reported as AU/ml as described elsewhere 19 . P values < 0.05…”

Section: Interferometry (Bli)mentioning

confidence: 99%

“…In parallel, we measured the titers of IgG, IgM, and IgA against RBD, spike, and protein N using a direct ELISA approach (Figure 4), which was published recently 19 . The neutralization potency, and spike titers, respectively, than any of the convalescent patient groups.…”

Section: Measurement Of Neutralization Potency and Antibody Titers Inmentioning

confidence: 99%

“…We benchmarked our assay with the PRNT and two commercially available tests. Using a previously described cohort of PCR-confirmed COVID-19 convalescent patients 19 , we measured the neutralization potency and the relative titers of IgG, IgM, and…”

Section: Introductionmentioning

confidence: 99%

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Vaccine monitoring shows that focused immunization with SARS-CoV-2 receptor-binding domain provides a better neutralizing antibody response than full-length spike protein

Bayarri‐Olmos

Idorn

Rosbjerg

et al. 2021

Preprint

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Effective tools to monitor SARS-CoV-2 transmission and humoral immune responses are highly needed. Protective humoral immunity involves neutralizing antibodies and will be a hallmark for the evaluation of a vaccine response efficacy. Here we present a sensitive, fast and simple neutralization ELISA method to determine the levels of antibody-mediated virus neutralization. We can show that it is strongly correlated with the more elaborate plaque reduction neutralization test (PRNT) (ρ = 0.9231, p < 0.0001). Furthermore, we present pre-clinical vaccine models using recombinant receptor binding domain (RBD) and full-length spike antigen as immunogens showing a profound antibody neutralization capacity that exceeds the highest neutralization titers from convalescent individuals. Using a panel of novel high-affinity murine monoclonal antibodies (mAbs) we also show that majority of the RBD-raised mAbs have inhibitory properties while only a few of the spike-raised mAbs do. In conclusion, the ELISA-based viral neutralization test offers a time- and cost-effective alternative to the PRNT. The immunization results indicate that vaccine strategies focused only on the RBD region may have major advantages over those based on the full spike sequence.

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Section: Production and Purification Of Recombinant Ace-2 Ectodomain mentioning

confidence: 53%

Section: Production and Purification Of Recombinant Ace-2 Ectodomain mentioning

confidence: 99%

“…Antibodies were captured directly from supernatants. Briefly, 1 four-parameter non-linear curve fitting and reported as AU/ml as described elsewhere 19 . P values < 0.05…”

Section: Interferometry (Bli)mentioning

confidence: 99%

Section: Measurement Of Neutralization Potency and Antibody Titers Inmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Vaccine monitoring shows that focused immunization with SARS-CoV-2 receptor-binding domain provides a better neutralizing antibody response than full-length spike protein

Bayarri‐Olmos

Idorn

Rosbjerg

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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Humoral immunity against SARS‐CoV‐2 variants including omicron in solid organ transplant recipients after three doses of a COVID‐19 mRNA vaccine

et al. 2022

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Objectives Solid organ transplant recipients (SOTR) receiving post‐transplant immunosuppression show increased COVID‐19‐related mortality. It is unclear whether an additional dose of COVID‐19 vaccines can overcome the reduced immune responsiveness against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants. Methods We analysed humoral immune responses against SARS‐CoV‐2 and its variants in 53 SOTR receiving SARS‐CoV‐2 vaccination. Results Following the initial vaccination series, 60.3% of SOTR showed no measurable neutralisation and only 18.9% demonstrated neutralising activity of > 90%. More intensive immunosuppression, antimetabolites in particular, negatively impacted antiviral immunity. While absolute IgG levels were lower in SOTR than controls, antibody titres against microbial recall antigens were higher. By contrast, SOTR showed reduced vaccine‐induced IgG/IgA antibody titres against SARS‐CoV‐2 and its delta variants and fewer linear B‐cell epitopes, indicating reduced B‐cell diversity. Importantly, a third vaccine dose led to an increase in anti‐SARS‐CoV‐2 antibody titres and neutralising activity across alpha, beta and delta variants and to the induction of anti‐SARS‐CoV‐2 CD4 + T cells in a subgroup of patients analysed. By contrast, we observed significantly lower antibody titres after the third dose with the omicron variant compared to the ancestral SARS‐CoV‐2 and the improvement in neutralising activity was much less pronounced than for all the other variants. Conclusion Only a small subgroup of solid organ transplant recipients is able to generate functional antibodies after an initial vaccine series; however, an additional vaccine dose resulted in dramatically improved antibody responses against all SARS‐CoV‐2 variants except omicron where antibody responses and neutralising activity remained suboptimal.

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Immunologic features of asymptomatic postvaccination infections with the Delta variant of SARS‐CoV‐2 in adults

Duan

Mao

Ding

et al. 2022

Immunity Inflam & Disease

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Background Asymptomatic infections may play an important role in severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) Delta variant transmissions. However, the immunologic features of asymptomatic postvaccination infections with the Delta variant of SARS‐CoV‐2 in adults remain to be defined. Methods A retrospective study involving 36 vaccinated adults infected with the SARS‐CoV‐2 Delta variant was performed. Their demographic and laboratory data were collected and analyzed in The First People's Hospital of Jingmen from August 4 to 20, 2021. Results Of the 36 adults, 6 persons had an asymptomatic infection. The severity of the SARS‐CoV‐2 infections was highly correlated with the doses of vaccinations (p = 0.019). The symptomatic and asymptomatic infected SARS‐CoV‐2 adults showed normal levels of leukocytes and lymphocytes. The C‐reactive protein (CRP) and interleukin‐6 (IL‐6) levels were elevated in the symptomatic groups. The period between the last vaccination to the time of infection in the asymptomatic group was longer than that in the mild and moderate groups (73 vs. 61 vs. 50 days; p = 0.047). The percentage of suppressor T‐cells in the asymptomatic group was the highest (32.2 ± 4.0% vs. 22.0 ± 7.2% vs. 29.3 ± 8.0%; p = 0.004). The signal‐to‐cutoff ratio value of total antibody against SARS‐CoV‐2 in the asymptomatic group was lower than that in the other two groups (383 vs. 703 vs. 1792; p < 0.001) and much lower than that in the moderate group. The multivariate ordinal logistic analysis after adjusting for gender, vaccination date, and vaccination dose indicated that CRP at Days 4−7 and 8−14, IL‐6 on Days 4−7, and total antibody were risk factors for coronavirus disease 2019 severity. Conclusions Asymptomatic postvaccination infections with the Delta variant of SARS‐CoV‐2 in adults tend to infect persons vaccinated twice. The immunophenotype profile for asymptomatic postvaccination infections is less inflammatory and accompanied by relatively lower antibody titers.

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SARS-CoV-2 Antibody Responses Are Correlated to Disease Severity in COVID-19 Convalescent Individuals

Cited by 112 publications

References 31 publications

Vaccine monitoring shows that focused immunization with SARS-CoV-2 receptor-binding domain provides a better neutralizing antibody response than full-length spike protein

Vaccine monitoring shows that focused immunization with SARS-CoV-2 receptor-binding domain provides a better neutralizing antibody response than full-length spike protein

Humoral immunity against SARS‐CoV‐2 variants including omicron in solid organ transplant recipients after three doses of a COVID‐19 mRNA vaccine

Immunologic features of asymptomatic postvaccination infections with the Delta variant of SARS‐CoV‐2 in adults

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