scholarly journals Activity of convalescent and vaccine serum against a B.1.1.529 variant SARS-CoV-2 isolate

2021 ◽  
Author(s):  
Juan Manuel Carreno ◽  
Hala Alshammary ◽  
Johnstone Tcheou ◽  
Gagandeep Singh ◽  
Ariel Raskin ◽  
...  
Keyword(s):  
South Africa ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Escape ◽  
Metropolitan Areas ◽  
Binding Activity ◽  
Receptor Binding Domain ◽  
Type B ◽  
Wild Type ◽  
Neutralizing Activity ◽  
Spike Gene

The B.1.1.529 (Omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in November of 2021 in South Africa and Botswana as well as in a sample of a traveler from South Africa in Hong Kong.1,2 Since then, B.1.1.529 has been detected in many countries globally. This variant seems to be more infectious than B.1.617.2 (Delta), has already caused super spreader events3 and has outcompeted Delta within weeks in several countries and metropolitan areas. B.1.1.529 hosts an unprecedented number of mutations in its spike gene and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness.2,4-6 Here, we investigated the neutralizing and binding activity of sera from convalescent, mRNA double vaccinated, mRNA boosted as well as convalescent double vaccinated and convalescent boosted individuals against wild type, B.1.351 and B.1.1.529 SARS-CoV-2 isolates. Neutralizing activity of sera from convalescent and double vaccinated participants was undetectable to very low against B.1.1.529 while neutralizing activity of sera from individuals who had been exposed to spike three or four times was maintained, albeit at strongly reduced levels. Binding to the B.1.1.529 receptor binding domain (RBD) and N-terminal domain (NTD) was reduced in convalescent not vaccinated but was mostly retained in vaccinated individuals.

scholarly journals Murine monoclonal antibodies against RBD of SARS-CoV-2 neutralize authentic wild type SARS-CoV-2 as well as B.1.1.7 and B.1.351 viruses and protect in vivo in a mouse model in a neutralization dependent manner

2021 ◽  
Author(s):  
Fatima Amanat ◽  
Shirin Strohmeier ◽  
Wen-Hsin Lee ◽  
Sandhya Bangaru ◽  
Andrew B Ward ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Mouse Model ◽  
Neutralizing Antibodies ◽  
Dependent Manner ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Murine Monoclonal Antibodies

After first emerging in December 2019 in China, severe acute respiratory syndrome 2 (SARS-CoV-2) has since caused a pandemic leading to millions of infections and deaths worldwide. Vaccines have been developed and authorized but supply of these vaccines is currently limited. With new variants of the virus now emerging and spreading globally, it is essential to develop therapeutics that are broadly protective and bind conserved epitopes in the receptor binding domain (RBD) or the whole spike of SARS-CoV-2. In this study, we have generated mouse monoclonal antibodies (mAbs) against different epitopes on the RBD and assessed binding and neutralization against authentic SARS-CoV-2. We have demonstrated that antibodies with neutralizing activity, but not non-neutralizing antibodies, lower viral titers in the lungs when administered in a prophylactic setting in vivo in a mouse challenge model. In addition, most of the mAbs cross-neutralize the B.1.351 as well as the B.1.1.7 variants in vitro.

scholarly journals A synthetic bispecific antibody capable of neutralizing SARS-CoV-2 Delta and Omicron

2022 ◽  
Author(s):  
Tom Z Yuan ◽  
Carolina Lucas ◽  
Valter S Monteiro ◽  
Akiko Iwasaki ◽  
Marisa L Yang ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Bispecific Antibody ◽  
Immune Escape ◽  
Binding Domain ◽  
Bispecific Antibodies ◽  
Receptor Binding Domain ◽  
Promising Strategy

Bispecific antibodies have emerged as a promising strategy for curtailing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune escape. This brief report highlights RBT-0813 (also known as TB493-04), a synthetic, humanized, receptor-binding domain (RBD)-targeted bispecific antibody that retains picomolar affinity to the Spike (S) trimers of all major variants of concern and neutralizes both SARS-CoV-2 Delta and Omicron in vitro.

scholarly journals Local emergence and decline of a SARS-CoV-2 variant with mutations L452R and N501Y in the spike protein

2021 ◽  
Author(s):  
Jan-Philipp Mallm ◽  
Christian Bundschuh ◽  
Heeyoung Kim ◽  
Niklas Weidner ◽  
Simon Steiger ◽  
...  
Keyword(s):  
Amino Acid ◽  
Severe Acute Respiratory Syndrome ◽  
Type Strain ◽  
Wild Type Strain ◽  
Population Level ◽  
Spike Protein ◽  
Whole Genome ◽  
Wild Type ◽  
Spike Gene ◽  
Mutational Pattern

SummaryVariants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are replacing the initial wild-type strain, jeopardizing current efforts to contain the pandemic. Amino acid exchanges in the spike protein are of particular concern as they can render the virus more transmissible or reduce vaccine efficacy. Here, we conducted whole genome sequencing of SARS-CoV-2 positive samples from the Rhine-Neckar district in Germany during January-March 2021. We detected a total of 166 samples positive for a variant with a distinct mutational pattern in the spike gene comprising L18F, L452R, N501Y, A653V, H655Y, D796Y and G1219V with a later gain of A222V. This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains. These observations strongly argue for continuous and comprehensive monitoring of SARS-CoV-2 evolution on a population level.

scholarly journals SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma

2021 ◽  
Vol 118 (36) ◽  
pp. e2103154118 ◽  
Author(s):  
Emanuele Andreano ◽  
Giulia Piccini ◽  
Danilo Licastro ◽  
Lorenzo Casalino ◽  
Nicole V. Johnson ◽  
...  
Keyword(s):  
South Africa ◽  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Receptor Binding Domain ◽  
The United Kingdom ◽  
Effective Immune Response ◽  
Recent Emergence ◽  
Natural Variants

To investigate the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the immune population, we coincupi bated the authentic virus with a highly neutralizing plasma from a COVID-19 convalescent patient. The plasma fully neutralized the virus for seven passages, but, after 45 d, the deletion of F140 in the spike N-terminal domain (NTD) N3 loop led to partial breakthrough. At day 73, an E484K substitution in the receptor-binding domain (RBD) occurred, followed, at day 80, by an insertion in the NTD N5 loop containing a new glycan sequon, which generated a variant completely resistant to plasma neutralization. Computational modeling predicts that the deletion and insertion in loops N3 and N5 prevent binding of neutralizing antibodies. The recent emergence in the United Kingdom, South Africa, Brazil, and Japan of natural variants with similar changes suggests that SARS-CoV-2 has the potential to escape an effective immune response and that vaccines and antibodies able to control emerging variants should be developed.

scholarly journals Sensitivity of SARS-CoV-2 Variants to Neutralization by Convalescent Sera and a VH3-30 Monoclonal Antibody

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuai Yue ◽  
Zhirong Li ◽  
Yao Lin ◽  
Yang Yang ◽  
Mengqi Yuan ◽  
...  
Keyword(s):  
South Africa ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Binding Activity ◽  
Wild Type ◽  
The Past ◽  
Global Pandemic ◽  
Neutralizing Capacity ◽  
Novel Coronavirus ◽  
Medical Countermeasures

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). Though vaccines and neutralizing monoclonal antibodies (mAbs) have been developed to fight COVID-19 in the past year, one major concern is the emergence of SARS-CoV-2 variants of concern (VOCs). Indeed, SARS-CoV-2 VOCs such as B.1.1.7 (UK), B.1.351 (South Africa), P.1 (Brazil), and B.1.617.1 (India) now dominate the pandemic. Herein, we found that binding activity and neutralizing capacity of sera collected from convalescent patients in early 2020 for SARS-CoV-2 VOCs, but not non-VOC variants, were severely blunted. Furthermore, we observed evasion of SARS-CoV-2 VOCs from a VH3-30 mAb 32D4, which was proved to exhibit highly potential neutralization against wild-type (WT) SARS-CoV-2. Thus, these results indicated that SARS-CoV-2 VOCs might be able to spread in convalescent patients and even harbor resistance to medical countermeasures. New interventions against these SARS-CoV-2 VOCs are urgently needed.

scholarly journals Multiplex qPCR discriminates variants of concern to enhance global surveillance of SARS-CoV-2

PLoS Biology ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. e3001236
Author(s):  
Chantal B. F. Vogels ◽  
Mallery I. Breban ◽  
Isabel M. Ott ◽  
Tara Alpert ◽  
Mary E. Petrone ◽  
...  
Keyword(s):  
South Africa ◽  
United Kingdom ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Primary Target ◽  
Pcr Assay ◽  
Gene Target ◽  
Spike Gene ◽  
The United Kingdom ◽  
The World

With the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants that may increase transmissibility and/or cause escape from immune responses, there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant, first detected in the United Kingdom, could be serendipitously detected by the Thermo Fisher TaqPath Coronavirus Disease 2019 (COVID-19) PCR assay because a key deletion in these viruses, spike Δ69–70, would cause a “spike gene target failure” (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern (VOC) that lack spike Δ69–70, such as B.1.351 (also 501Y.V2), detected in South Africa, and P.1 (also 501Y.V3), recently detected in Brazil. We identified a deletion in the ORF1a gene (ORF1a Δ3675–3677) in all 3 variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a Δ3675–3677 as the primary target and spike Δ69–70 to differentiate, we designed and validated an open-source PCR assay to detect SARS-CoV-2 VOC. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence and spread of B.1.1.7, B.1.351, and P.1.

scholarly journals Ad26.COV2.S elicited neutralizing activity against Delta and other SARS-CoV-2 variants of concern

2021 ◽  
Author(s):  
Mandy Jongeneelen ◽  
Krisztian Kaszas ◽  
Daniel Veldman ◽  
Jeroen Huizingh ◽  
Remko van der Vlugt ◽  
...  
Keyword(s):  
Single Dose ◽  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Immune Evasion ◽  
Vaccine Coverage ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Neutralizing Activity ◽  
Fold Reduction ◽  
Pronounced Reduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and recently emerging variants with substitutions in the Spike protein have led to growing concerns over increased transmissibility and decreased vaccine coverage due to immune evasion. Here, sera from recipients of a single dose of our Ad26.COV2.S COVID-19 vaccine were tested for neutralizing activity against several SARS-CoV-2 variants of concern. All tested variants demonstrated susceptibility to Ad26.COV2.S-induced serum neutralization albeit mainly reduced as compared to the B.1 strain. Most pronounced reduction was observed for the B.1.351 (Beta; 3.6-fold) and P.1 (Gamma; 3.4-fold) variants that contain similar mutations in the receptor-binding domain (RBD) while only a 1.6-fold reduction was observed for the widely spreading B.1.617.2 (Delta) variant.

Considerable escape of SARS-CoV-2 variant Omicron to antibody neutralization

2021 ◽  
Author(s):  
Delphine Planas ◽  
Nell Saunders ◽  
Piet Maes ◽  
Florence Guivel Benhassine ◽  
Cyril Planchais ◽  
...  
Keyword(s):  
South Africa ◽  
Monoclonal Antibodies ◽  
Receptor Binding ◽  
Binding Domain ◽  
Viral Fitness ◽  
Receptor Binding Domain ◽  
Antibody Neutralization ◽  
Neutralizing Activity ◽  
Terminal Domain ◽  
Therapeutic Monoclonal Antibodies

The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa. It has in the meantime spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of about 32 mutations in the Spike, located mostly in the N-terminal domain (NTD) and the receptor binding domain (RBD), which may enhance viral fitness and allow antibody evasion. Here, we isolated an infectious Omicron virus in Belgium, from a traveller returning from Egypt. We examined its sensitivity to 9 monoclonal antibodies (mAbs) clinically approved or in development, and to antibodies present in 90 sera from COVID-19 vaccine recipients or convalescent individuals. Omicron was totally or partially resistant to neutralization by all mAbs tested. Sera from Pfizer or AstraZeneca vaccine recipients, sampled 5 months after complete vaccination, barely inhibited Omicron. Sera from COVID-19 convalescent patients collected 6 or 12 months post symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titers 5 to 31 fold lower against Omicron than against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and to a large extent vaccine-elicited antibodies.

scholarly journals Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Guillaume Beaudoin-Bussières ◽  
Annemarie Laumaea ◽  
Sai Priya Anand ◽  
Jérémie Prévost ◽  
Romain Gasser ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Active Infection ◽  
Positive Role ◽  
Neutralization Activity ◽  
Neutralizing Activity ◽  
Specific Igg ◽  
Alternative Approaches ◽  
Humoral Responses

ABSTRACT In the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for potential transfusion to coronavirus disease 2019 (COVID-19) patients. The therapy has been deemed safe, and several clinical trials assessing its efficacy are ongoing. While it remains to be formally proven, the presence of neutralizing antibodies is thought to play a positive role in the efficacy of this treatment. Indeed, neutralizing titers of ≥1:160 have been recommended in some convalescent plasma trials for inclusion. Here, we performed repeated analyses at 1-month intervals on 31 convalescent individuals to evaluate how the humoral responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein, including neutralization, evolve over time. We observed that the levels of receptor-binding-domain (RBD)-specific IgG and IgA slightly decreased between 6 and 10 weeks after the onset of symptoms but that RBD-specific IgM levels decreased much more abruptly. Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing wild-type SARS-CoV-2 S or its D614G variant. If neutralization activity proves to be an important factor in the clinical efficacy of convalescent plasma transfer, our results suggest that plasma from convalescent donors should be recovered rapidly after resolution of symptoms. IMPORTANCE While waiting for an efficient vaccine to protect against SARS-CoV-2 infection, alternative approaches to treat or prevent acute COVID-19 are urgently needed. Transfusion of convalescent plasma to treat COVID-19 patients is currently being explored; neutralizing activity in convalescent plasma is thought to play a central role in the efficacy of this treatment. Here, we observed that plasma neutralization activity decreased a few weeks after the onset of the symptoms. If neutralizing activity is required for the efficacy of convalescent plasma transfer, our results suggest that convalescent plasma should be recovered rapidly after the donor recovers from active infection.

scholarly journals Effects of common mutations in the SARS-CoV-2 Spike RBD domain and its ligand the human ACE2 receptor on binding affinity and kinetics

2021 ◽  
Author(s):  
Michael I Barton ◽  
Stuart MacGowan ◽  
Mikhail A Kutuzov ◽  
Omer Dushek ◽  
Geoffrey J Barton ◽  
...  
Keyword(s):  
South Africa ◽  
Cell Surface ◽  
Immune Escape ◽  
Surface Protein ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Cell Surface Protein ◽  
Kinetics Analysis ◽  
Protein Receptor ◽  
The Uk

The interaction between the SARS-CoV-2 virus Spike protein receptor binding domain (RBD) and the ACE2 cell surface protein is required for viral infection of cells. Mutations in the RBD domain are present in SARS-CoV-2 variants of concern that have emerged independently worldwide. For example, the more transmissible B.1.1.7 lineage has a mutation (N501Y) in its Spike RBD domain that enhances binding to ACE2. There are also ACE2 alleles in humans with mutations in the RBD binding site. Here we perform a detailed affinity and kinetics analysis of the effect of five common RBD mutations (K417N, K417T, N501Y, E484K and S477N) and two common ACE2 mutations (S19P and K26R) on the RBD/ACE2 interaction. We analysed the effects of individual RBD mutations, and combinations found in new SARS-CoV-2 variants first identified in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P1). Most of these mutations increased the affinity of the RBD/ACE2 interaction. The exceptions were mutations K417N/T, which decreased the affinity. Taken together with other studies, our results suggest that the N501Y and S477N mutations primarily enhance transmission, the K417N/T mutations facilitate immune escape, and the E484K mutation facilitates both transmission and immune escape.

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