Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(19)

Published: April 23, 2021

Significance Neutralizing antibodies are important for immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and as therapeutics the prevention treatment of COVID-19. We identified high-affinity nanobodies SARS-CoV-2 receptor-binding domain found that nanobody cocktails consisting two noncompeting were able to block ACE2 engagement with RBD variants present in human populations potently neutralize both wild-type N501Y D614G variant at low concentrations. Prophylactic administration reduced viral loads mice infected virus, showing useful prophylactic agents SARS-CoV-2.

Language: Английский

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ScanNet: an interpretable geometric deep learning model for structure-based protein binding site prediction

Nature Methods, Journal Year: 2022, Volume and Issue: 19(6), P. 730 - 739

Published: May 30, 2022

Language: Английский

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mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants

Immunity, Journal Year: 2021, Volume and Issue: 54(12), P. 2893 - 2907.e5

Published: Sept. 21, 2021

Language: Английский

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Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection

Science Immunology, Journal Year: 2022, Volume and Issue: 7(73)

Published: May 12, 2022

Understanding immune responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)–specific B cell Omicron/BA.1 in messenger RNA–vaccinated donors. The antibody response was characterized by high levels somatic hypermutation and a bias toward recognition ancestral SARS-CoV-2 strains, suggesting early activation vaccine-induced memory cells. BA.1 induced shift immunodominance hierarchy from S2 subunit, which is highly conserved across variants concern (VOCs), antigenically variable receptor binding domain (RBD). A large proportion RBD-directed neutralizing antibodies isolated donors displayed convergent sequence features broadly recognized VOCs. Together, these findings provide insights into role preexisting immunity shaping to heterologous variant exposure.

Language: Английский

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Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease

Immunity, Journal Year: 2023, Volume and Issue: 56(3), P. 669 - 686.e7

Published: Feb. 16, 2023

Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and more effectively respond SARS-CoV-2 variants. The emergence of Omicron subvariants illustrates limitations solely targeting receptor-binding domain (RBD) spike (S) protein. Here, we isolated a large panel (bnAbs) from recovered-vaccinated donors, which targets conserved S2 region in betacoronavirus fusion machinery. Select bnAbs showed broad vivo protection all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, MERS-CoV, have spilled over into humans past two decades. Structural studies these delineated molecular basis for their reactivity revealed common antibody features targetable by vaccination strategies. These provide new insights opportunities antibody-based interventions pan-betacoronavirus vaccines.

Language: Английский

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