Cross-reactive serum and memory B-cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection

Song, Ge; He, Wanting; Callaghan, Sean; Anzanello, Fabio; Huang, Deli; Ricketts, James; Torres, Jonathan L.; Beutler, Nathan; Peng, Linghang; Vargas, Sirena; Cassell, Jon; Parren, Mara; Yang, Linlin; Ignacio, Caroline; Smith, Davey M; Voss, James E.; Nemazee, David; Ward, Andrew B.; Rogers, Thomas F.; Burton, Dennis R.; Andrabi, Raiees

doi:10.1038/s41467-021-23074-3

Cited by 237 publications

(258 citation statements)

References 58 publications

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“…37 Our results demonstrate that FcgR-binding antibodies against betacoronaviruses OC43 and HKU1 are much higher in COVID-19 convalescent individuals compared to uninfected controls. This could either be due to the back boosting of preexisting HCoV antibodies that are cross-reactive with SARS-CoV-2 28,29 or the de novo generation of SARS-CoV-2 antibodies that are cross-reactive with conserved HCoV epitopes. Cross-reactive S antibodies were largely directed against the more conserved S2 subunit, in line with other reports, 28,29 which also likely explains the longer half-life of S2 antibodies that we observed relative to S1 antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…This could either be due to the back boosting of preexisting HCoV antibodies that are cross-reactive with SARS-CoV-2 28,29 or the de novo generation of SARS-CoV-2 antibodies that are cross-reactive with conserved HCoV epitopes. Cross-reactive S antibodies were largely directed against the more conserved S2 subunit, in line with other reports, 28,29 which also likely explains the longer half-life of S2 antibodies that we observed relative to S1 antibodies. A recent study found cross-reactive binding and neutralizing antibodies against SARS-CoV-2 S2 in uninfected children and adolescents, 28 suggesting prior infections with OC43 or HKU1 can elicit cross-reactive antibodies against the S2 subunit of SARS-CoV-2 S. These findings raise the interesting question of whether cross-reactive antibodies are recalled rapidly during early SARS-CoV-2 infection and can contribute to Fc effector functions against conserved epitopes within the S2 subunit.…”

Section: Discussionmentioning

confidence: 99%

“…Cross-reactive antibodies between endemic human coronaviruses (HCoVs) and SARS-CoV-2 have been widely reported, 28,29 suggesting past exposure to HCoVs may prime ADCC and ADP immunity against SARS-CoV-2. In addition, several studies have shown back boosting of antibodies against endemic HCoVs following infection with SARS-CoV-2, 30,31 likely due to the recall of pre-existing B cell responses against conserved regions of S. We thus determined whether IgG antibody levels against S from four HCoV strains (OC43, HKU1, 229E, and NL63; Table S2) were higher in COVID-19 convalescent subjects compared to uninfected healthy controls.…”

Section: Cross-reactivity With Hcov S-specific Antibodiesmentioning

confidence: 99%

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Decay of Fc-dependent antibody functions after mild to moderate COVID-19

Lee

Selva

Davis

et al. 2021

Cell Reports Medicine

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The capacity of antibodies to engage with immune cells via the Fc region is important in preventing and controlling many infectious diseases. The evolution of such antibodies during convalescence from COVID-19 is largely unknown. We develop assays to measure Fc-dependent antibody functions against SARS-CoV-2 spike (S)-expressing cells in serial samples from subjects primarily with mild-moderate COVID-19, up to 149 days post-infection. We find that S-specific antibodies capable of engaging Fcγ receptors decay over time, with S-specific antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP) activity within plasma declining accordingly. Although there is significant decay in ADCC and ADP activity, they remain readily detectable in almost all subjects at the last timepoint studied (94%) in contrast with neutralisation activity (70%). While it remains unclear the degree to which Fc effector functions contribute to protection against SARS-CoV-2 re-infection, our results indicate that antibodies with Fc effector functions persist longer than neutralising antibodies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cross-reactivity With Hcov S-specific Antibodiesmentioning

confidence: 99%

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Decay of Fc-dependent antibody functions after mild to moderate COVID-19

Lee

Selva

Davis

et al. 2021

Cell Reports Medicine

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“…It has been suggested S2 can be a target of the neutralizing antibody for SARS-CoV, MERS-CoV and SARS-CoV-2 [ 34 , 35 ]. Indeed, neutralizing antibodies targeting the S2 region have been found [36] . D796H mutation in the S2 region has been proposed to reduce neutralization susceptibility by convalescent plasma and is found in the B.1.1.318 [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum

Lu¹,

Chu²,

Zhang³

et al. 2021

eBioMedicine

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Background Several SARS-CoV-2 lineages with spike receptor binding domain (RBD) N501Y mutation have spread globally. We evaluated the impact of N501Y on neutralizing activity of COVID-19 convalescent sera and on anti-RBD IgG assays. Methods The susceptibility to neutralization by COVID-19 patients’ convalescent sera from Hong Kong were compared between two SARS-CoV-2 isolates (B117-1/B117-2) from the α variant with N501Y and 4 non-N501Y isolates. The effect of N501Y on antibody binding was assessed. The performance of commercially-available IgG assays was determined for patients infected with N501Y variants. Findings The microneutralization antibody (MN) titers of convalescent sera from 9 recovered COVID-19 patients against B117-1 (geometric mean titer[GMT],80; 95% CI, 47–136) were similar to those against the non-N501Y viruses. However, MN titer of these serum against B117-2 (GMT, 20; 95% CI, 11–36) was statistically significantly reduced when compared with non-N501Y viruses (P < 0.01; one-way ANOVA). The difference between B117-1 and B117-2 was confirmed by testing 60 additional convalescent sera. B117-1 and B117-2 differ by only 3 amino acids (nsp2-S512Y, nsp13-K460R, spike-A1056V). Enzyme immunoassay using 272 convalescent sera showed reduced binding of anti-RBD IgG to N501Y or N501Y-E484K-K417N when compared with that of wild-type RBD (mean difference: 0.1116 and 0.5613, respectively; one-way ANOVA). Of 7 anti-N-IgG positive sera from patients infected with N501Y variants (collected 9-14 days post symptom onset), 6 (85.7%) tested negative for a commercially-available anti-S1-IgG assay. Interpretation We highlighted the importance of using a panel of viruses within the same lineage to determine the impact of virus variants on neutralization. Furthermore, clinicians should be aware of the potential reduced sensitivity of anti-RBD IgG assays.

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“…Another important aspect to mention is that our study did not evaluate cross-reactivity with other coronaviruses, which could generate false positive results in the serological determinations. Serological studies showed cross-reactivity of SARS-CoV-2 S protein with SARS-CoV (the agent responsible for the 2003 epidemic), MERS (Middle East Respiratory Syndrome coronavirus), and sCOVs (seasonal coronaviruses) [25][26][27][28][29][30].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Properties of Three SARS-CoV-2 Antibody Tests

et al. 2021

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Serological assays emerged as complementary tools to RT-PCR in the diagnosis of SARS-CoV-2 as well as being needed for epidemiological studies. This study aimed to assess the performance of a rapid test (RT) compared to that of serological tests using finger prick blood samples. A total of 183 samples were evaluated, 88 of which were collected from individuals with negative RT-PCR and 95 from positive RT-PCR individuals. The diagnostic performance of RT (WONDFO®) and LUMIT (PROMEGA®) were compared to that of ELISA (EUROIMMUN®) for detecting antibodies against SARS-CoV-2 according to time from symptoms onset. The IgG antibody tests were detected in 77.4% (LUMIT), 77.9% (RT), and 80.0% (ELISA) of individuals. The detection of antibodies against SARS-CoV-2 increases in accordance with increasing time from symptoms onset. Considering only time from symptoms onset >21 days, the positivity rate ranged from 81.8 to 97.0% between the three tests. The RT and LUMIT showed high agreement with ELISA (agreement = 91.5%, k = 0.83, and agreement = 96.3%, k = 0.9, respectively) in individuals who had symptoms 15 to 21 days before sample collection. Compared to that of the ELISA assay, our results show sensitivity ranged from 95% to 100% for IgG antibody detection in individuals with symptoms onset between 15 and 21 days before sample collection. The specificity was 100% in individuals with symptoms onset >15 days before serological tests. This study shows good performance and high level of agreement of three immunoassays for the detection of SARS-CoV-2 antibodies.

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Cross-reactive serum and memory B-cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection

Cited by 237 publications

References 58 publications

Decay of Fc-dependent antibody functions after mild to moderate COVID-19

Decay of Fc-dependent antibody functions after mild to moderate COVID-19

The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum

Diagnostic Properties of Three SARS-CoV-2 Antibody Tests

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