Serum Neutralizing Activity of mRNA-1273 against SARS-CoV-2 Variants

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has led to growing concerns over increased transmissibility and the ability of some variants to partially escape immunity. Sera from participants immunized on a prime-boost schedule with the mRNA-1273 COVID-19 vaccine were tested for neutralizing activity against several SARS-CoV-2 variants, including variants of concern (VOCs) and variants of interest (VOIs), compared to neutralization of the wild-type SARS-CoV-2 virus (designated as D614G). Results showed minimal, statistically non-significant effects on neutralization titers against the B.1.1.7 (Alpha) variant (1.2-fold reduction compared with D614G); other VOCs such as B.1.351 (Beta, including B.1.351-v1, B.1.351-v2, and B.1.351-v3), P.1 (Gamma), and B.1.617.2 (Delta), showed significantly decreased neutralization titers ranging from 2.1-fold to 8.4-fold reductions compared with D614G, although all remained susceptible to mRNA-1273–elicited serum neutralization. IMPORTANCE In light of multiple variants of SARS-CoV-2 that have been documented globally during the COVID-19 pandemic, it remains important to continually assess the ability of currently available vaccines to confer protection against newly emerging variants. Data presented herein indicate that immunization with the mRNA-1273 COVID-19 vaccine produces neutralizing antibodies against key emerging variants tested, including variants of concern and variants of interest. While the serum neutralization elicited by mRNA-1273 against most variants tested was reduced compared with the wild-type virus, they are still expected to be protective. Such data are crucial to inform ongoing and future vaccination strategies to combat COVID-19.

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

10.1101/2021.07.01.450707 ◽

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.

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The rise and fall of an emerging SARS-CoV-2 variant with the spike protein mutation L452R

10.1101/2021.07.03.21259957 ◽

2021 ◽

Author(s):

Orna Mor ◽

Michal Mandelboim ◽

Shay Fleishon ◽

Efrat Bucris ◽

Dana Bar-Ilan ◽

...

Keyword(s):

Wild Type Strain ◽

Disease Spread ◽

Wild Type ◽

Neutralization Capacity ◽

Protein Mutation ◽

Routine Surveillance ◽

Fold Reduction ◽

Novel Variants ◽

Novel Variant ◽

Alpha Variant

Emerging SARS-CoV-2 variants may threaten global vaccination efforts and awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants among efforts undertaken to prevent further disease spread.

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mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 Omicron variant

10.1101/2021.12.20.473557 ◽

2021 ◽

Author(s):

Venkata-Viswanadh Edara ◽

Kelly E Manning ◽

Madison Ellis ◽

Lilin Lai ◽

Kathryn M Moore ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Neutralization Assay ◽

Antibody Responses ◽

Spike Protein ◽

Live Virus ◽

Neutralizing Activity ◽

Virus Neutralization Assay ◽

Fold Reduction

The BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines generate potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the global emergence of SARS-CoV-2 variants with mutations in the spike protein, the principal antigenic target of these vaccines, has raised concerns over the neutralizing activity of vaccine-induced antibody responses. The Omicron variant, which emerged in November 2021, consists of over 30 mutations within the spike protein. Here, we used an authentic live virus neutralization assay to examine the neutralizing activity of the SARS-CoV-2 Omicron variant against mRNA vaccine-induced antibody responses. Following the 2nd dose, we observed a 30-fold reduction in neutralizing activity against the omicron variant. Through six months after the 2nd dose, none of the sera from naive vaccinated subjects showed neutralizing activity against the Omicron variant. In contrast, recovered vaccinated individuals showed a 22-fold reduction with more than half of the subjects retaining neutralizing antibody responses. Following a booster shot (3rd dose), we observed a 14-fold reduction in neutralizing activity against the omicron variant and over 90% of boosted subjects showed neutralizing activity against the omicron variant. These findings show that a 3rd dose is required to provide robust neutralizing antibody responses against the Omicron variant.

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Vaccination with B.1.1.7, B.1.351 and P.1 variants protects mice from challenge with wild type SARS-CoV-2

10.1101/2021.08.05.455212 ◽

2021 ◽

Author(s):

Fatima Amanat ◽

Shirin Strohmeier ◽

Philip Meade ◽

Nicholas Dambrauskas ◽

Barbara Mühlemann ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Recombinant Protein ◽

Mouse Model ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Wild Type ◽

Fold Reduction ◽

Reactive Antibody

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been highly efficient in protecting against coronavirus disease 2019 (COVID-19). However, the emergence of viral variants that are more transmissible and, in some cases, escape from neutralizing antibody responses has raised concerns. Here, we evaluated recombinant protein spike antigens derived from wild type SARS-CoV-2 and from variants B.1.1.7, B.1.351 and P.1 for their immunogenicity and protective effect in vivo against challenge with wild type SARS-CoV-2 in the mouse model. All proteins induced high neutralizing antibodies against the respective viruses but also induced high cross-neutralizing antibody responses. The decline in neutralizing titers between variants was moderate, with B.1.1.7 vaccinated animals having a maximum fold reduction of 4.8 against B.1.351 virus. P.1 induced the most cross-reactive antibody responses but was also the least immunogenic in terms of homologous neutralization titers. However, all antigens protected from challenge with wild type SARS-CoV-2 in a mouse model.

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The Rise and Fall of a Local SARS-CoV-2 Variant with the Spike Protein Mutation L452R

Vaccines ◽

10.3390/vaccines9080937 ◽

2021 ◽

Vol 9 (8) ◽

pp. 937

Author(s):

Orna Mor ◽

Michal Mandelboim ◽

Shay Fleishon ◽

Efrat Bucris ◽

Dana Bar-Ilan ◽

...

Keyword(s):

Wild Type Strain ◽

Disease Spread ◽

Wild Type ◽

Neutralization Capacity ◽

Protein Mutation ◽

Routine Surveillance ◽

Fold Reduction ◽

Novel Variants ◽

Novel Variant ◽

Alpha Variant

Emerging SARS-CoV-2 variants may threaten global vaccination efforts and the awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants among efforts undertaken to prevent further disease spread.

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

10.1101/2021.12.20.21268134 ◽

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.

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Delayed neutralizing antibody response in the acute phase correlates with severe progression of COVID-19

Scientific Reports ◽

10.1038/s41598-021-96143-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hitoshi Kawasuji ◽

Yoshitomo Morinaga ◽

Hideki Tani ◽

Miyuki Kimura ◽

Hiroshi Yamada ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Neutralization Test ◽

Neutralizing Antibody ◽

Pseudotyped Virus ◽

Serum Samples ◽

Neutralization Activity ◽

Neutralizing Activity ◽

Time Points ◽

Moderate Disease ◽

Activity Dynamics

AbstractAdaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Using SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. Of the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2–12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9–16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P = .011). Neutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.

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Purification and characterization of a nonpolymerizing long-pitch actin dimer

Biochemistry and Cell Biology ◽

10.1139/o06-091 ◽

2006 ◽

Vol 84 (5) ◽

pp. 695-702 ◽

Cited By ~ 1

Author(s):

Braden Sweeting ◽

John F. Dawson

Keyword(s):

Critical Concentration ◽

Dnase I ◽

Actin Binding ◽

Wild Type ◽

Filamentous Actin ◽

Rhodamine Phalloidin ◽

Fold Reduction ◽

Crystallization Conditions ◽

Self Association ◽

Pointed End

Atomic resolution structures of filamentous actin have not been obtained owing to the self-association of actin under crystallization conditions. Obtaining short filamentous actin complexes of defined lengths is therefore a highly desirable goal. Here we report the production and isolation of a long-pitch actin dimer employing chemical crosslinking between wild-type actin and Q41C/C374A mutant actin. The Q41C/C374A mutant actin possessed altered polymerization properties, with a 2-fold reduction in the rate of elongation and an increased critical concentration relative to wild-type actin. The Q41C/C374A mutant actin also displayed an increase in the IC50 for DNase I, a pointed-end actin-binding protein. The long-pitch dimer was bound by DNase I to prevent polymerization and purified. It was found that each actin dimer is bound by 2 DNase I molecules, 1 likely bound to each of the actin protomers. The long-pitch dimer bound by DNase I did not form short F actin structures, as assessed by the binding of rhodamine–phalloidin.

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Synthesis of Trypsin-Resistant Variants of the Listeria-Active Bacteriocin Salivaricin P

Applied and Environmental Microbiology ◽

10.1128/aem.00523-10 ◽

2010 ◽

Vol 76 (16) ◽

pp. 5356-5362 ◽

Cited By ~ 22

Author(s):

Eileen F. O'Shea ◽

Paula M. O'Connor ◽

Paul D. Cotter ◽

R. Paul Ross ◽

Colin Hill

Keyword(s):

Antimicrobial Activity ◽

Gastrointestinal Tract ◽

Cleavage Sites ◽

Wild Type ◽

Enhanced Resistance ◽

Fold Reduction ◽

Two Component ◽

Specific Protease ◽

The Individual ◽

Protease Action

ABSTRACT Two-component salivaricin P-like bacteriocins have demonstrated potential as antimicrobials capable of controlling infections in the gastrointestinal tract (GIT). The anti-Listeria activity of salivaricin P is optimal when the individual peptides Sln1 and Sln2 are added in succession at a 1:1 ratio. However, as degradation by digestive proteases may compromise the functionality of these peptides within the GIT, we investigated the potential to create salivaricin variants with enhanced resistance to the intestinal protease trypsin. A total of 11 variants of the salivaricin P components, in which conservative modifications at the trypsin-specific cleavage sites were explored in order to protect the peptides from trypsin degradation while maintaining their potent antimicrobial activity, were generated. Analysis of these variants revealed that eight were resistant to trypsin digestion while retaining antimicrobial activity. Combining the complementary trypsin-resistant variants Sln1-5 and Sln2-3 resulted in a MIC50 of 300 nM against Listeria monocytogenes, a 3.75-fold reduction in activity compared to the level for wild-type salivaricin P. This study demonstrates the potential of engineering bacteriocin variants which are resistant to specific protease action but which retain significant antimicrobial activity.

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