A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies

Wang, Chunyan; Haperen, Rien van; Gutiérrez-Álvarez, Javier; Li, Wentao; Okba, Nisreen M.A.; Albulescu, Irina C.; Widjaja, Ivy; Dieren, Brenda van; Fernández‐Delgado, Raúl; Sola, Isabel; Hurdiss, Daniel L.; Daramola, Olalekan; Grosveld, Frank; Kuppeveld, Frank J. M. van; Haagmans, Bart L.; Enjuanes, Luis; Drabek, Dubravka; Bosch, Berend-Jan

doi:10.1038/s41467-021-21968-w

Cited by 154 publications

(179 citation statements)

References 84 publications

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“…SARS-CoV-2–uninfected children and adolescents are more likely than adults to contain these cross reactive and ‘protective’ antibodies ( 31 ). These findings support that immunogenic sites of the spike protein are conserved between other CoV and SARS-CoV-2 ( 32 ).…”

Section: Jaks and The Immunological Responsesupporting

confidence: 82%

The Many Faces of JAKs and STATs Within the COVID-19 Storm

et al. 2021

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The positive-sense single stranded RNA virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), resulted in a global pandemic with horrendous health and economic consequences not seen in a century. At a finer scale, immunologically, many of these devastating effects by SARS-CoV-2 can be traced to a “cytokine storm” resulting in the simultaneous activation of Janus Kinases (JAKs) and Signal Transducers and Activators of Transcription (STAT) proteins downstream of the many cytokine receptor families triggered by elevated cytokines found in Coronavirus Disease 2019 (COVID-19). In this report, cytokines found in the storm are discussed in relation to the JAK-STAT pathway in response to SARS-CoV-2 and the lessons learned from RNA viruses and previous Coronaviruses (CoVs). Therapeutic strategies to counteract the SARS-CoV-2 mediated storm are discussed with an emphasis on cell signaling and JAK inhibition.

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Section: Jaks and The Immunological Responsesupporting

confidence: 82%

The Many Faces of JAKs and STATs Within the COVID-19 Storm

et al. 2021

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“…The development of universal vaccination strategies against Sarbecoviruses will be improved by the identification and characterization of broadly protective and conserved epitopes across SARS-like virus strains. Recent studies described broadly reactive antibodies that target the subunit 2 (S2) portion of the spike protein [28][29][30][31] . While the broad recognition of these S2specific antibodies is encouraging, these antibodies weakly neutralized diverse CoVs.…”

Section: Discussionmentioning

confidence: 99%

A broadly neutralizing antibody protects against SARS-CoV, pre-emergent bat CoVs, and SARS-CoV-2 variants in mice

Martinez

Schaefer

Gobeil

et al. 2021

Preprint

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SARS-CoV in 2003, SARS-CoV-2 in 2019, and SARS-CoV-2 variants of concern (VOC) can cause deadly infections, underlining the importance of developing broadly effective countermeasures against Group 2B Sarbecoviruses, which could be key in the rapid prevention and mitigation of future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV, bat CoVs WIV-1 and RsSHC014, and SARS-CoV-2 variants D614G, B.1.1.7, B.1.429, B1.351 by a receptor-binding domain (RBD)-specific antibody DH1047. Prophylactic and therapeutic treatment with DH1047 demonstrated protection against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B1.351infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among Sarbecoviruses. We conclude that DH1047 is a broadly neutralizing and protective antibody that can prevent infection and mitigate outbreaks caused by SARS-like strains and SARS-CoV-2 variants. Our results argue that the RBD conserved epitope bound by DH1047 is a rational target for pan Group 2B coronavirus vaccines.

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“…The SARS-CoV-2 spike (S) protein, which includes the receptor binding domain (RBD), is key to cell entry for the virus and thus, was the primary target of all currently approved vaccines in Europe [16] . In addition to the spike protein, coronaviruses, including SARS-CoV-2, encode three other structural proteins, namely the envelope (E), membrane (M) and nucleocapsid (N) proteins, all of which evoke robust and detectable immune responses [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

B and T cell response to SARS-CoV-2 vaccination in health care professionals with and without previous COVID-19

et al. 2021

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Background In recent months numerous health care professional acquired COVID-19 at the workplace resulting in significant shortages in medical and nursing staff. We investigated how prior COVID-19 affects SARS-CoV-2 vaccination and how such knowledge could facilitate frugal vaccination strategies. Methods In a cohort of 41 healthcare professionals with (n=14) and without (n=27) previous SARS-CoV-2 infection, we assessed the immune status before, during and after vaccination with BNT162b2. The humoral immune response was assessed by receptor binding domain ELISA and different SARS-CoV-2 neutralisation assays using wildtype and pseudo-typed viruses. T cell immunity against SARS-CoV-2 surface and nucleocapsid peptides were studied using interferon-γ release assays and intracellular flow cytometry. Vaccine-related side effects were captured. Findings Prior COVID-19 resulted in improved vaccine responses both in the B and T cell compartment. In vaccine recipients with prior COVID-19, the first vaccine dose induced high antibody concentrations comparable to seronegative vaccine recipients after two injections. This translated into more efficient neutralisation of virus particles, even more pronounced than expected from the RBD ELISA results. Furthermore, T cell responses were stronger in convalescents and particularly strong against the SARS-CoV-2 nucleocapsid protein. Interpretation Herein, we corroborate recent findings suggesting that in convalescents a single vaccine dose is sufficient to boost adequate in vitro neutralisation of SARS-CoV-2 and therefore may be sufficient to induce adequate protection against severe COVID-19. New spike mutated virus variants render the highly conserved nucleocapsid protein – eliciting strong SARS-CoV-2 specific T cell immunity – an interesting additional vaccine target. Funding Christian Doppler Research Association, Johannes Kepler University Linz

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A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies

Cited by 154 publications

References 84 publications

The Many Faces of JAKs and STATs Within the COVID-19 Storm

The Many Faces of JAKs and STATs Within the COVID-19 Storm

A broadly neutralizing antibody protects against SARS-CoV, pre-emergent bat CoVs, and SARS-CoV-2 variants in mice

B and T cell response to SARS-CoV-2 vaccination in health care professionals with and without previous COVID-19

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