Potent universal beta-coronavirus therapeutic activity mediated by direct respiratory administration of a Spike S2 domain-specific human neutralizing monoclonal antibody DOI Creative Commons
Michael S. Piepenbrink, Jun‐Gyu Park,

Ashlesha Deshpande

et al.

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(7), P. e1010691 - e1010691

Published: July 21, 2022

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) marks the third novel β-coronavirus to cause significant human mortality in last two decades. Although vaccines are available, too few have been administered worldwide keep virus check and prevent mutations leading immune escape. To determine if antibodies could be identified with universal coronavirus activity, plasma from convalescent subjects was screened for IgG against a stabilized pre-fusion SARS-CoV-2 spike S2 domain, which is highly conserved between β-coronavirus. From these subjects, several S2-specific monoclonal (hmAbs) were developed that neutralized recognition of all variants concern (VoC) tested (Beta, Gamma, Delta, Epsilon, Omicron). The hmAb 1249A8 emerged as most potent broad hmAb, able recognize neutralize SARS-CoV MERS-CoV. demonstrated prophylactic activity K18 hACE2 mice infected lineage A B Beta, Omicron VoC. delivered single 4 mg/kg intranasal (i.n.) dose hamsters 12 hours following infection Delta protected them weight loss, therapeutic further enhanced when combined 1213H7, an S1-specific neutralizing hmAb. As little 2 i.n. Urbani strain, loss significantly reduced upper lower respiratory viral burden. These results indicate vivo cooperativity S1 specific hmAbs mAbs potential can induced humans guide vaccine development.

Language: Английский

A human antibody reveals a conserved site on beta-coronavirus spike proteins and confers protection against SARS-CoV-2 infection DOI Creative Commons
Pan-Pan Zhou, Meng Yuan, Ge Song

et al.

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(637)

Published: Feb. 8, 2022

Broadly neutralizing antibodies (bnAbs) to coronaviruses (CoVs) are valuable in their own right as prophylactic and therapeutic reagents treat diverse CoVs templates for rational pan-CoV vaccine design. We recently described a bnAb, CC40.8, from CoV disease 2019 (COVID-19) convalescent donor that exhibits broad reactivity with human β-CoVs. Here, we showed CC40.8 targets the conserved S2 stem helix region of spike fusion machinery. determined crystal structure Fab SARS-CoV-2 peptide at 1.6-Å resolution found adopted mainly helical structure. Conserved residues β-CoVs interacted antibody, thereby providing molecular basis its reactivity. exhibited vivo protective efficacy against challenge two animal models. In both models, CC40.8-treated animals less weight loss reduced lung viral titers compared controls. Furthermore, noted CC40.8-like bnAbs relatively rare COVID-19 infection, therefore, elicitation may require structure-based design strategies. Overall, our study describes target on β-CoV proteins facilitate development pan–β-CoV vaccines.

Language: Английский

Citations

166
Viral persistence, reactivation, and mechanisms of long COVID DOI Creative Commons
Benjamin K. Chen,

Boris Jülg,

Sindhu Mohandas

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 4, 2023

The COVID-19 global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has infected hundreds of millions individuals. Following infection, a subset can develop wide range chronic symptoms affecting diverse organ systems referred to as post-acute sequelae SARS-CoV-2 (PASC), also known long COVID. A National Institutes Health-sponsored initiative, RECOVER: Researching COVID Enhance Recovery, sought understand basis in large cohort. Given that occur COVID, mechanisms may underlie these be diverse. In this review, we focus on emerging literature supporting role(s) viral persistence or reactivation viruses play PASC. Persistence RNA antigens is reported some organs, yet mechanism which they do so and how associated with pathogenic immune responses unclear. Understanding RNA, antigen other reactivated relate specific inflammatory drive PASC provide rationale for treatment.

Language: Английский

Citations

144
mRNA-1273 and BNT162b2 COVID-19 vaccines elicit antibodies with differences in Fc-mediated effector functions DOI Creative Commons
Paulina Kapłonek, Deniz Cizmeci, Stephanie Fischinger

et al.

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(645)

Published: March 29, 2022

The successful development of several coronavirus disease 2019 (COVID-19) vaccines has substantially reduced morbidity and mortality in regions the world where have been deployed. However, wake emergence viral variants that are able to evade vaccine-induced neutralizing antibodies, real-world vaccine efficacy begun show differences across two approved mRNA platforms, BNT162b2 mRNA-1273; these findings suggest subtle variation immune responses induced by mRNA-1273 may confer differential protection. Given our emerging appreciation for importance additional antibody functions beyond neutralization, we profiled postboost binding functional capacity humoral a cohort hospital staff. Both robust wild-type severe acute respiratory syndrome 2 (SARS-CoV-2) concern. emerged epitope-specific responses, with higher concentrations receptor domain (RBD)- N-terminal domain-specific IgA observed recipients mRNA-1273. Antibodies eliciting neutrophil phagocytosis natural killer cell activation were also increased as compared recipients. RBD-specific depletion highlighted different roles non-RBD-specific effector vaccines. These data provide insights into potential protective immunity conferred

Language: Английский

Citations

124
Antibody-mediated neutralization of SARS-CoV-2 DOI Creative Commons

Henning Gruell,

Kanika Vanshylla, Timm Weber

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(6), P. 925 - 944

Published: May 13, 2022

Language: Английский

Citations

120
Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease DOI Creative Commons
Pan-Pan Zhou, Ge Song,

Hejun Liu

et al.

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

Citations

120
SARS-CoV-2 S2–targeted vaccination elicits broadly neutralizing antibodies DOI Creative Commons
Kevin W. Ng, Nikhil Faulkner, Katja Finsterbusch

et al.

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(655)

Published: July 27, 2022

Several variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged during the current disease 2019 (COVID-19) pandemic. Although antibody cross-reactivity with spike glycoproteins (S) diverse coronaviruses, including endemic common cold coronaviruses (HCoVs), has been documented, it remains unclear whether such responses, typically targeting conserved S2 subunit, contribute to protection when induced by infection or through vaccination. Using a mouse model, we found that prior HCoV-OC43 S–targeted immunity primes neutralizing responses otherwise subimmunogenic SARS-CoV-2 S exposure and promotes S2-targeting responses. Moreover, vaccination elicited antibodies in mice neutralized animal human alphacoronaviruses betacoronaviruses vitro provided degree against challenge vivo. Last, history Wuhan–based vaccination, further broader response than booster Wuhan suggesting may prevent repertoire focusing caused repeated homologous These data establish protective value an vaccine support notion better prepare immune system respond changing nature S1 subunit concern, as well future zoonoses.

Language: Английский

Citations

88
Advances and gaps in SARS-CoV-2 infection models DOI Creative Commons
César Muñoz‐Fontela, Lina Widerspick, Randy A. Albrecht

et al.

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(1), P. e1010161 - e1010161

Published: Jan. 13, 2022

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants concern (VOCs). Preclinical models disease, in particular animal models, are essential investigate VOC pathogenesis, correlates protection postexposure therapies. Here, we provide an update from World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances preclinical models. In particular, discuss how model research playing a key role evaluate virulence, transmission immune escape, being refined recapitulate demographic variables comorbidities age.

Language: Английский

Citations

79
Maternal immune response and placental antibody transfer after COVID-19 vaccination across trimester and platforms DOI Creative Commons
Caroline Atyeo, Lydia L. Shook, Sara Brigida

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 28, 2022

The availability of three COVID-19 vaccines in the United States provides an unprecedented opportunity to examine how vaccine platforms and timing vaccination pregnancy impact maternal neonatal immunity. Here, we characterize antibody profile after Ad26.COV2.S, mRNA-1273 or BNT162b2 158 pregnant individuals evaluate transplacental transfer by profiling umbilical cord blood 175 maternal-neonatal dyads. These analyses reveal lower vaccine-induced functions Fc receptor-binding Ad26.COV2.S compared mRNA subtle advantages titer function with versus BN162b2. have higher titers against SARS-CoV-2 variants concern. First third trimester results enhanced antibody-dependent NK-cell activation, cellular neutrophil phagocytosis, complement deposition relative second trimester. Higher ratios following first may reflect placental compensation for waning titers. provide novel insight into platform on humoral immune response transfer.

Language: Английский

Citations

77
Enhancing the immunogenicity of lipid-nanoparticle mRNA vaccines by adjuvanting the ionizable lipid and the mRNA DOI
Bowen Li, Allen Yujie Jiang,

Idris Raji

et al.

Nature Biomedical Engineering, Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 7, 2023

Language: Английский

Citations

77
Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors DOI Creative Commons
Levente Zsichla, Viktor Müller

Viruses, Journal Year: 2023, Volume and Issue: 15(1), P. 175 - 175

Published: Jan. 7, 2023

The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease death. Understanding the risk factors is relevant both in setting at epidemiological level. Here, we provide an overview host, viral environmental that have been shown or (in some cases) hypothesized be associated with outcomes. considered detail include age frailty, genetic polymorphisms, biological sex (and pregnancy), co- superinfections, non-communicable comorbidities, immunological history, microbiota, lifestyle patient; variation infecting dose; socioeconomic factors; air pollution. For each category, compile (sometimes conflicting) evidence for association factor outcomes (including strength effect) outline possible action mechanisms. We also discuss complex interactions between various factors.

Language: Английский

Citations

71