John E. Bowen
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View article: Back to the Future: Long-Term Leadership Lessons From the COVID-19 Pandemic
Back to the Future: Long-Term Leadership Lessons From the COVID-19 Pandemic Open
Senior leaders must balance clinical necessity with humanistic values and purpose. Situation awareness and attention to organizational culture may improve the quality, timeliness, and effectiveness of responses to the next pandemic threat.
View article: Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features
Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features Open
In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe–critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 v…
View article: SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines
SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines Open
Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit a…
View article: Imprinted antibody responses against SARS-CoV-2 Omicron sublineages
Imprinted antibody responses against SARS-CoV-2 Omicron sublineages Open
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boost…
View article: Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape
Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape Open
SUMMARY Memory B cells (MBCs) generate rapid antibody responses upon secondary encounter with a pathogen. Here, we investigated the kinetics, avidity and cross-reactivity of serum antibodies and MBCs in 155 SARS-CoV-2 infected and vaccinat…
View article: Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines
Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines Open
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern comprises several sublineages, with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1 and with BA.4 and BA.5 increasing in prevalence…
View article: ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies
ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies Open
The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus spike proteins from seve…
View article: Imprinted antibody responses against SARS-CoV-2 Omicron sublineages
Imprinted antibody responses against SARS-CoV-2 Omicron sublineages Open
SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in pot…
View article: Multivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice
Multivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice Open
New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression workflow to rapidly screen and optimize const…
View article: ACE2 engagement exposes the fusion peptide to pan-coronavirus neutralizing antibodies
ACE2 engagement exposes the fusion peptide to pan-coronavirus neutralizing antibodies Open
Coronaviruses use diverse Spike (S) glycoproteins to attach to host receptors and fuse with target cells. Using a broad screening approach, we isolated from SARS-CoV-2 immune donors seven monoclonal antibodies (mAbs) that bind to all human…
View article: Omicron BA.1 and BA.2 neutralizing activity elicited by a comprehensive panel of human vaccines
Omicron BA.1 and BA.2 neutralizing activity elicited by a comprehensive panel of human vaccines Open
The SARS-CoV-2 Omicron variant of concern comprises three sublineages designated BA.1, BA.2, and BA.3, with BA.2 steadily replacing the globally dominant BA.1. We show that the large number of BA.1 and BA.2 spike mutations severely dampen …
View article: Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement
Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement Open
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to accumulation of numerous spike mutations. T…
View article: A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy
A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy Open
Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by e…
View article: Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail
Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail Open
The SARS-CoV-2 receptor-binding domain (RBD) E406W mutation abrogates neutralization mediated by the REGEN-CoV therapeutic monoclonal antibody (mAb) COVID-19 cocktail and the cilgavimab (AZD1061) mAb. Here, we show that this residue substi…
View article: Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry
Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry Open
Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and future zoonotic sarbecoviruses. We describe the isola…
View article: Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement
Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement Open
The SARS-CoV-2 Omicron variant of concern evades antibody mediated immunity with an unprecedented magnitude due to accumulation of numerous spike mutations. To understand the Omicron antigenic shift, we determined cryo-electron microscopy …
View article: Molecular basis of immune evasion by the Delta and Kappa SARS-CoV-2 variants
Molecular basis of immune evasion by the Delta and Kappa SARS-CoV-2 variants Open
How the Delta variant evades defenses In the course of the COVID-19 epidemic, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, some of which evade immunity or increase transmission. In late 2020,…
View article: SARS-CoV-2 spike conformation determines plasma neutralizing activity
SARS-CoV-2 spike conformation determines plasma neutralizing activity Open
Numerous safe and effective COVID-19 vaccines have been developed that utilize various delivery technologies and engineering strategies. The influence of the SARS-CoV-2 spike (S) glycoprotein conformation on antibody responses induced by v…
View article: SARS-CoV-2 Omicron spike mediated immune escape and tropism shift
SARS-CoV-2 Omicron spike mediated immune escape and tropism shift Open
The SARS-CoV-2 Omicron BA.1 variant emerged in late 2021 and is characterised by multiple spike mutations across all spike domains. Here we show that Omicron BA.1 has higher affinity for ACE2 compared to Delta, and confers very significant…
View article: Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift
Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift Open
SUMMARY The recently emerged SARS-CoV-2 Omicron variant harbors 37 amino acid substitutions in the spike (S) protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vacci…
View article: Delta breakthrough infections elicit potent, broad and durable neutralizing antibody responses
Delta breakthrough infections elicit potent, broad and durable neutralizing antibody responses Open
The SARS-CoV-2 Delta variant is currently responsible for most infections worldwide, including among fully vaccinated individuals. Although these latter infections are associated with milder COVID-19 disease relative to unvaccinated subjec…
View article: Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry
Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry Open
Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures effective against SARS-CoV-2 variants and future spillovers of other sarbecoviruses. Here we describe the isolation and characterizatio…