scholarly journals Binding and Neutralizing Antibody Responses to SARS-CoV-2 in Infants and Young Children Exceed Those in Adults

2021 ◽  
Author(s):  
Ruth A. Karron ◽  
Maria Garcia Quesada ◽  
Elizabeth A. Schappell ◽  
Stephen D. Schmidt ◽  
Maria Deloria Knoll ◽  
...  
Keyword(s):  
Young Children ◽  
Immune Responses ◽  
Receptor Binding ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Binding Antibody ◽  
Infants And Young Children

SARS-CoV-2 infections are frequently milder in children than adults, suggesting that immune responses may vary with age. However, information is limited regarding SARS-CoV-2 immune responses in young children. We compared Receptor Binding Domain binding antibody (RBDAb) and SARS-CoV-2 neutralizing antibody (neutAb) in children aged 0-4 years, 5-17 years, and in adults aged 18-62 years in a SARS-CoV-2 household study. Among 55 participants seropositive at enrollment, children aged 0-4 years had >10-fold higher RBDAb titers than adults (373 vs.35, P<0.0001), and the highest RBDAb titers in 11/12 households with seropositive children and adults. Children aged 0-4 years had 2-fold higher neutAb than adults, resulting in higher binding to neutralizing (B/N)Ab ratios compared to adults (1.9 vs. 0.4 for ID50, P=0.0002). Findings suggest that young children mount robust antibody responses to SARS-CoV-2 following community infections. Additionally, these results support using neutAb to measure the immunogenicity of COVID-19 vaccines in children aged 0-4 years.

scholarly journals Sex Disparities and Neutralizing-Antibody Durability to SARS-CoV-2 Infection in Convalescent Individuals

mSphere ◽  
2021 ◽  
Vol 6 (4) ◽  
Author(s):  
Alena J. Markmann ◽  
Natasa Giallourou ◽  
D. Ryan Bhowmik ◽  
Yixuan J. Hou ◽  
Aaron Lerner ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Antibody Titers ◽  
Sex Disparities ◽  
Binding Antibody ◽  
Male Sex ◽  
Antibody Levels

In this study, we found that neutralizing antibody responses in COVID-19-convalescent individuals vary in magnitude but are durable and correlate well with receptor binding domain (RBD) Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex.

scholarly journals Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice

2020 ◽  
Author(s):  
Alexander A. Cohen ◽  
Priyanthi N.P. Gnanapragasam ◽  
Yu E. Lee ◽  
Pauline R. Hoffman ◽  
Susan Ou ◽  
...  
Keyword(s):  
Immune Responses ◽  
Receptor Binding ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Antibody Responses ◽  
Soluble Antigen ◽  
Receptor Binding Domain ◽  
Potential Strategy

AbstractProtection against SARS-CoV-2 and SARS-related emergent zoonotic coronaviruses is urgently needed. We made homotypic nanoparticles displaying the receptor-binding domain (RBD) of SARS-CoV-2 or co-displaying SARS-CoV-2 RBD along with RBDs from animal betacoronaviruses that represent threats to humans (mosaic nanoparticles; 4-8 distinct RBDs). Mice immunized with RBD-nanoparticles, but not soluble antigen, elicited cross-reactive binding and neutralization responses. Mosaic-RBD-nanoparticles elicited antibodies with superior cross-reactive recognition of heterologous RBDs compared to sera from immunizations with homotypic SARS-CoV-2–RBD-nanoparticles or COVID-19 convalescent human plasmas. Moreover, sera from mosaic-RBD–immunized mice neutralized heterologous pseudotyped coronaviruses equivalently or better after priming than sera from homotypic SARS-CoV-2–RBD-nanoparticle immunizations, demonstrating no immunogenicity loss against particular RBDs resulting from co-display. A single immunization with mosaic-RBD-nanoparticles provides a potential strategy to simultaneously protect against SARS-CoV-2 and emerging zoonotic coronaviruses.One sentence summaryNanoparticle strategy for pan-sarbecovirus vaccine125-character summary for online ToCImmunizing with nanoparticles displaying diverse coronavirus RBDs elicits cross-reactive and neutralizing antibody responses.

scholarly journals SARS-CoV-2 Neutralizing Antibody Responses towards Full-Length Spike Protein and the Receptor-Binding Domain

2021 ◽  
pp. ji2100272
Author(s):  
Rafael Bayarri-Olmos ◽  
Manja Idorn ◽  
Anne Rosbjerg ◽  
Laura Pérez-Alós ◽  
Cecilie Bo Hansen ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Antibody Responses ◽  
Full Length ◽  
Spike Protein ◽  
Receptor Binding Domain

scholarly journals Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies

2020 ◽  
Author(s):  
Christopher O. Barnes ◽  
Anthony P. West ◽  
Kathryn E. Huey-Tubman ◽  
Magnus A.G. Hoffmann ◽  
Naima G. Sharaf ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Receptor Binding ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Human Antibodies ◽  
Antibody Class

SummaryNeutralizing antibody responses to coronaviruses focus on the trimeric spike, with most against the receptor-binding domain (RBD). Here we characterized polyclonal IgGs and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their degree of focus on RBD epitopes, recognition of SARS-CoV, MERS-CoV, and mild coronaviruses, and how avidity effects contributed to increased binding/neutralization of IgGs over Fabs. Electron microscopy reconstructions of polyclonal plasma Fab-spike complexes showed recognition of both S1A and RBD epitopes. A 3.4Å cryo-EM structure of a neutralizing monoclonal Fab-S complex revealed an epitope that blocks ACE2 receptor-binding on “up” RBDs. Modeling suggested that IgGs targeting these sites have different potentials for inter-spike crosslinking on viruses and would not be greatly affected by identified SARS-CoV-2 spike mutations. These studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.

Peptide Antidotes to SARS-CoV-2 (COVID-19)

2020 ◽  
Author(s):  
Andre Watson ◽  
Leonardo Ferreira ◽  
Peter Hwang ◽  
Jinbo Xu ◽  
Robert Stroud
Keyword(s):  
Immune Responses ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Spike Protein ◽  
Binding Motif ◽  
Receptor Binding Domain ◽  
Specificity And Sensitivity ◽  
Peptide Scaffolds

ABSTRACTThe design of an immunogenic scaffold that serves a role in treating a pathogen, and can be rapidly and predictively modeled, has remained an elusive feat. Here, we demonstrate that SARS-BLOCK™ synthetic peptide scaffolds act as antidotes to SARS-CoV-2 spike protein-mediated infection of human ACE2-expressing cells. Critically, SARS-BLOCK™ peptides are able to potently and competitively inhibit SARS-CoV-2 S1 spike protein receptor binding domain (RBD) binding to ACE2, the main cellular entry pathway for SARS-CoV-2, while also binding to neutralizing antibodies against SARS-CoV-2. In order to create this potential therapeutic antidote-vaccine, we designed, simulated, synthesized, modeled epitopes, predicted peptide folding, and characterized behavior of a novel set of synthetic peptides. The biomimetic technology is modeled off the receptor binding motif of the SARS-CoV-2 coronavirus, and modified to provide enhanced stability and folding versus the truncated wildtype sequence. These novel peptides attain single-micromolar binding affinities for ACE2 and a neutralizing antibody against the SARS-CoV-2 receptor binding domain (RBD), and demonstrate significant reduction of infection in nanomolar doses. We also demonstrate that soluble ACE2 abrogates binding of RBD to neutralizing antibodies, which we posit is an essential immune-evasive mechanism of the virus. SARS-BLOCK™ is designed to “uncloak” the viral ACE2 coating mechanism, while also binding to neutralizing antibodies with the intention of stimulating a specific neutralizing antibody response. Our peptide scaffolds demonstrate promise for future studies evaluating specificity and sensitivity of immune responses to our antidote-vaccine. In summary, SARS-BLOCK™ peptides are a promising COVID-19 antidote designed to combine the benefits of a therapeutic and vaccine, effectively creating a new generation of prophylactic and reactive antiviral therapeutics whereby immune responses can be enhanced rather than blunted.

scholarly journals An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope

2021 ◽  
Author(s):  
Zezhong Liu ◽  
Wei Xu ◽  
Zhenguo Chen ◽  
Wangjun Fu ◽  
Wuqiang Zhan ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibody ◽  
Cross Reactivity ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Binding Antibody ◽  
Neutralizing Epitopes ◽  
Conserved Epitope ◽  
Induce Antibody

AbstractNew threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional “down” conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD “up”. Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.

scholarly journals 480 Preliminary evaluation of a novel coronavirus vaccine (CORVax) using electroporation of plasmid DNA encoding a stabilized prefusion SARS-CoV-2 spike protein alone or with transfection of plasmid IL-12

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A514-A514
Author(s):  
Shawn Jensen ◽  
Christopher Twitty ◽  
Christopher Paustian ◽  
Madelein Laws ◽  
Glenna McDonnell ◽  
...  
Keyword(s):  
Immune Responses ◽  
Receptor Binding ◽  
Binding Domain ◽  
Tumor Rejection ◽  
Spike Protein ◽  
Preliminary Evaluation ◽  
List Type ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Viral Neutralization

BackgroundSARS-CoV-2 (CoV2) has precipitated a global pandemic and the effectiveness of standard vaccine strategies to induce potent and persistent immunity to CoV2 is in question, particularly for the elderly. This problem is not dissimilar to what we have struggled with in our quest to induce immunity to cancer antigens, where vaccine-induced anti-cancer immune responses can be weak. Here, we describe a novel vaccine approach which leverages electroporation (EP) of a plasmid encoding a prefusion stabilized CoV2 spike protein (CORVax). As IL-12 has been shown to augment the efficacy of immunotherapy in aged mice,1 we have initiated studies to evaluate if plasmid IL-12 (TAVO™) can similarly augment anti-CoV2 immune responses in young mice and have planned studies in aged animals.MethodsA prefusion stabilized CoV2 spike plasmid expression vector was constructed, a master cell bank generated and clinical-grade plasmid manufactured. C57BL/6 and BALB/c were vaccinated via intramuscular (IM) and/or intradermal (ID) injection followed immediately by EP of plasmids encoding the CoV2 spike protein with or without plasmid-encoded murine IL-12 on days 1 and 14 or 21. Mice were followed for >120 days to assess safety. Splenocytes and serum were harvested at different time points to interrogate virus-specific cellular responses as well anti-spike IgG1/IgG2 antibody titers. A surrogate viral neutralization test (sVNT) assessed serum blockade of soluble hACE2R binding to immobilized CoV2 spike.ResultsPreliminary data shows that EP of CORVax alone or combined with IL-12 was safe. EP of CORVax was able to elicit anti-Spike IgG antibodies (IC50 = 1/2112), as well as IgG antibodies targeting the receptor binding domain of the Spike protein (IC50 = 1/965) approximately 40 days after the booster vaccination. In 2 of 2 experiments, CORVax combined with IL-12 significantly (P<0.0001) increased the sVNT titers at 2 months, but this benefit was lost by 3 months.ConclusionsEarly preclinical data shows that EP of CORVax can induce IgG responses to CoV2 Spike and the receptor binding domain (RBD) as well as apparent viral neutralizing activity. The addition of IL-12, at least transiently, increased sVNT titer. We plan to investigate alternate vaccine boosting strategies while extending these studies into aged animals and initiate a clinical trial in the near future.ReferencesRuby CE, Weinberg AD. OX40-Enhanced tumor rejection and effector T cell differentiation decreases with age. J Immunol2009;182:1481–9. https://doi.org/10.4049/jimmunol.182.3.1481.

Sign in / Sign up

Export Citation Format

Share Document