Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses

Feldman, Jared; Bals, Julia; Altomare, Clara G.; Denis, Kerri J St; Lam, Evan C.; Hauser, Blake M.; Ronsard, Larance; Sangesland, Maya; Moreno, Thalia Bracamonte; Okonkwo, Vintus; Hartojo, Nathania; Balazs, Alejandro B.; Bajic, Goran; Lingwood, Daniel; Schmidt, Aaron

doi:10.1101/2021.02.02.429458

Cited by 11 publications

(13 citation statements)

References 137 publications

(182 reference statements)

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“…1C). The reactivity to the RBD antigen observed in most of the acute outpatients with COVID-19 indicate activation of the humoral response and is suggestive of the development of neutralizing antibodies with the capacity to block SARS-COV-2 spike protein interaction with its cognate receptor ACE-2 as previously reported [17, 20]. The presence of viral RNA without serological response suggests false-positive PCR or atypical antibody responses, which have been reported in some patients [17, 21].…”

Section: Discusionsupporting

confidence: 65%

Antibody response to SARS-CoV-2 infection over six months among Nicaraguan outpatients

González

Zepeda

Toval-Ruíz

et al. 2021

Preprint

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New information is emerging about SARS-CoV-2 epidemiology and immunity, but little of this information comes from low- and middle-income countries or from patients receiving care in the outpatient setting. The current study investigated the SARS-CoV-2 infection status and antibody responses in 157 patients seeking care for a respiratory disease suggestive of COVID-19 in private healthcare clinics during the first wave (June-October 2020) of infections in Nicaragua. We examined nasal swabs for the presence of viral RNA via RT-PCR and longitudinally collected sera for the changes in SARS-CoV-2 Spike antibody levels over six months. Among patients with confirmed SARS-CoV-2 infections, we evaluated if clinical symptoms were associated with age, hematological parameters and co-morbidities. The combination of PCR and paired serology identified 60 (38%) of the 157 outpatients as acute COVID-19. While both PCR and serology identified the majority (n = 38, 64%) of the acute infections, a notable number of outpatients were identified by RT-qPCR (n = 13, 22%) or by serology (n = 9, 14%) only. During the longitudinal study, we identified 6 new infections by serology among the 97 non-COVID-19 subjects. In conclusion, this study report that more than one third of the outpatients seeking care for acute respiratory disease during the first epidemic wave of SARS-CoV-2 in Nicaragua had an acute mild COVID-19 infection that correlate with prolonged humoral response. This immune response to the RBD antigen, more likely IgG dependent, significantly increased between the acute to convalescent and decay in the late convalescent but still remained seropositive.

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Section: Discusionsupporting

confidence: 65%

Antibody response to SARS-CoV-2 infection over six months among Nicaraguan outpatients

González

Zepeda

Toval-Ruíz

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Recently, through the analysis of human naïve B cells, some naïve antibodies have been shown to bind to the receptor-binding domain of SARS-CoV-2 and can neutralize SARS-CoV-2 pseudoviruses even in the absence of somatic mutations (11,12). Furthermore, although the clinical settings are different from our study, kidney transplant recipients and dialysis patients have diminished humoral responses to BNT162b2 with reduced B cells (13).…”

Section: Main Textmentioning

confidence: 53%

Immunological features that determine the strength of antibody responses to BNT162b2 mRNA vaccine against SARS-CoV-2

Kageyama

Tanaka

Etori

et al. 2021

Preprint

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We analyzed peripheral blood mononuclear cells (PBMCs) of each 20 individuals with a high anti-SARS-CoV-2 antibody titer and a low antibody titer out of 1,774 healthcare workers who received BNT162b2 mRNA vaccine. A higher antibody titer was associated with the frequencies of naive and transitional B cells before vaccination. In addition, fold changes in the frequency of activated CD8+ T cells upon vaccination were correlated with the antibody titers.

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“…CoV-2 ACE2 receptor binding domain (RBD), albeit weakly, and may be engaged upon vaccine exposure to generate germinal centers and then follow affinity maturation process [48,49]. Indeed, Rincon-Arevalo et al observed a significant difference in the frequency of SARS-CoV-2 RBD-specific naïve B cells between BNT162b2-responders and nonresponders [50].…”

Section: Discussionmentioning

confidence: 99%

BNT162b2 vaccine-induced humoral and cellular responses against SARS-CoV-2 variants in Systemic Lupus Erythematosus

Moyon

Sterlin

Miyara

et al. 2021

Preprint

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ObjectivesOur aims were to evaluate Systemic Lupus Erythematosus (SLE) disease activity and SARS-CoV-2 specific immune responses after BNT162b2 vaccination.MethodsIn this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine, until day 15 after the second dose in 126 SLE patients. SARS-CoV-2 antibody responses were measured against wild-type spike antigen while serum-neutralizing activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T-cell responses were quantified by Interferon (IFN)-γ release assay after the second dose.ResultsBNT162b2 was well tolerated and no statistically significant variations of BILAG and SLEDAI scores were observed throughout the study in SLE patients with active and inactive disease at baseline. Mycophenolate Mofetil (MMF) and Methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody-response (β=-78; p=0.007, β=-122; p<0.001, respectively). Anti-spike antibody response was positively associated with baseline total IgG serum levels, naïve B cell frequencies (β=2; p=0.018, β=2.5; p=0.003) and SARS-CoV-2-specific T cell response (r=0.462; p=0.003). In responders, serum neutralization activity decreased against VOCs bearing the E484K mutation but remained detectable in a majority of patients.ConclusionMMF, MTX and poor baseline humoral immune status, particularly: low naïve B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating SLE patients who might need adapted vaccine regimens and follow-up.KEY MESSAGESWhat is already known about this subject?BNT162b2 efficacy and safety has been described in studies mixing different RMDsWhat does this study add?No serious adverse effects, nor SLE flares have been documented after BNT162b2 in SLE patients.Not only MMF and MTX, but also a poor humoral immune status at baseline impair vaccine antibody responseAlbeit decreased, serum neutralizing activity against VOCs is conferred to vaccine-responders.How might this impact on clinical practice or future developments?These parameters could be helpful for physicians to delineate which patients should have antibody measurement after full BNT162b2 vaccination and should be proposed a third injection of BNT162b2 vaccine.

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Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses

Cited by 11 publications

References 137 publications

Antibody response to SARS-CoV-2 infection over six months among Nicaraguan outpatients

Antibody response to SARS-CoV-2 infection over six months among Nicaraguan outpatients

Immunological features that determine the strength of antibody responses to BNT162b2 mRNA vaccine against SARS-CoV-2

BNT162b2 vaccine-induced humoral and cellular responses against SARS-CoV-2 variants in Systemic Lupus Erythematosus

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