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Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants

TL;DR: The data suggest that control of emergent SARS-CoV-2 variants may benefit from updated vaccines, and that herd immunity may fail to eliminate the virus.
Abstract: The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia outbreak in Wuhan, China Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 'variants of concern' (VOC) across diverse geographic locales suggests herd immunity may fail to eliminate the virus All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B117 (501YV1) and B1351 (501YV2) Using a replication-competent EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV-G, and coupled with a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that only 1 out of 12 serum samples from a cohort of recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) of rcVSV-CoV2-S: B1351 at full serum strength The same set of sera efficiently neutralized S from B117 and showed only moderately reduced activity against S carrying the E484K substitution alone Taken together, our data suggest that control of some emergent SARS-CoV-2 variants may benefit from updated vaccines

Summary (3 min read)

INTRODUCTION.

  • The recent emergence of novel SARS-CoV-2 variants has reignited concerns that the pandemic may not be so easily brought under control.
  • The P.2 lineage, originally detected in Rio de Janeiro, carries only the E484K mutation in the RBD and has spread to other parts of South America, including Argentina 30 .
  • Since the Sputnik vaccine is now in use not only in Russia, but also in countries like Argentina, Mexico, and Hungary, where some of the VOC and emerging lineages bearing the E484K mutation are more widespread, it is critical to assess the neutralizing activity of Sputnik vaccine elicited antibody responses against these cognate VOC and mutant spikes.

SARS-CoV-2 Spike proteins.

  • Several groups have now generated replication-competent VSV expressing SARS-CoV-2 spike in place of VSV-G (rcVSV-CoV2-S) [35] [36] [37].
  • To generate rcVSV-CoV2-S containing different variants or mutants on demand, without the need for extensive passaging, the authors developed a robust reverse genetics system and VNA which leverages the cell lines they previously developed for a standardized SARS-CoV-2 VNA that correlates well with live virus neutralization 41 .
  • The characteristics of the vaccine recipient cohort (n=12) receiving the twodose regimen of the Sputnik vaccine are given in Table 1 .
  • The Hill slope of their neutralization curves for B.1.351 were extremely shallow (h<0.40), resulting in a low IC50s and maximal neutralization of 50-60% even when extrapolated to full serum strength (Fig. 3E and Fig. 4 ).
  • This 1.5 to 2-fold increase in RBD-Fc Experimental measurements of both RBD and trimeric spike binding to ACE2 have revealed that the E484K mutation alone does not confer increase binding affinity for ACE2 unlike N501Y 44, 46 .

DISCUSSION

  • A key public health concern related to emergent SARS-CoV-2 variants is that by incrementally accruing mutations that escape neutralizing antibodies, they will penetrate herd immunity and spread to reach unvaccinated individuals, some of whom will be susceptible to severe or fatal disease.
  • Even more revealing is their dose-response curves.
  • The neutralization curves for B.1.351 in their study are not classically sigmodal and have significantly shallower slopes than WT, B.1.17 and E484K, which result in ≤ 90% neutralization for all but one sample when extrapolated to full serum strength.
  • While the E484K substitution appears to be a common route of escape from many RBD-targeting monoclonal antibodies, it is somewhat surprising that a single mutation can confer a significant degree of neutralization resistance from polyclonal responses.
  • Even in the case of infection by VOC, their data reveal a concerning potential of B.1.351, and to a lesser extent, any variant carrying the E484K substitution (e.g. P.2), to escape the neutralizing antibody responses that this immunization elicits.the authors.

Cell lines

  • The HEK 293T-hACE2-TMPRSS2 cells were plated on collagen coated plates or dishes.
  • BSR-T7 cells 61 , which stably express T7-polymerase were maintained in DMEM with 10% FBS.
  • These accessory plasmids were a kind gift from Dr. Benjamin tenOever.

Generation of VSV-CoV2 spike from cDNA

  • 30 min later, transfection mixture was applied to 293T-hACE2-TMPRSS2 cells in a dropwise fashion.
  • Cells were maintained with medium replacement every day for 4 to 5 days until GFP positive syncytia appeared.
  • Rescued viruses were amplified in Vero-CCL81 TMPRSS2 cells 41 , then titered and used for the assay.

Virus neutralization assay

  • 5 x 10E4 293T-hACE2-TMPRSS2 cells per well were seeded onto collagen-coated 96 well cluster plates one day prior to use in viral neutralization assays.
  • Virus stocks were mixed with serially diluted serum for 10 minutes at room temperature, then infected to cells.
  • At 10 h post infection, GFP counts were counted by Celigo imaging cytometer .
  • For calculation of IC50, GFP counts from "no serum" conditions were set to 100%; GFP counts of each condition (serum treated) were normalized to no serum control well.
  • Inhibition curves were generated using Prism 8.4.3 (GraphPad Software) with 'log vs normalized response -variable slope' settings.

Design of RBD-Fc producing Sendai virus

  • Sendai virus (SeV) Z strain cDNA sequence (AB855655.1) was generated and cloned into pRS vector with the addition of eGFP transcriptional unit at the head of SeV genome.
  • The sequence of F transcriptional unit was from SeV fushimi strain (KY295909.1) due to the cloning reason.
  • The authors refer to the pRS-based plasmid coding this sequence as pRS-SeVZ-GFP-F fushimi in this paper.
  • RBD-Fc construct was generated as below; codon optimized DNA sequence of from SARS-CoV-2 spike (MN908947) in pCAGGS a gift of Dr. Florian Krammer 64 .

Generation of recombinant Sendai virus from cDNA.

  • 2x10E5 BSR-T7 cells per well were seeded onto 6-well cluster plates.
  • At one day post transfection, medium was replaced with DMEM + 0.2 µg/ml of TPCK-trypsin (Millipore Sigma, #T1426), with subsequent medium replacement each day until infection reached 100% cytopathic effect.
  • Supernatants were stored at -80˚C until use in experiments.

Titration of viruses.

  • GFP positive foci were counted at 24 hours post infection using a Celigo imaging cytometer (Nexcelom, Inc.).
  • Infectivity is presented in infectious units (IU) per mL. For VSV-CoV2 titration, 5 x 10E4 293T-hACE2-TMPRSS2 cells per well were seeded onto a collagen-coated 96 well plate.
  • Serially diluted virus stocks were then applied to the cells, and GFP positivity was scored at 10 h post infection using a Celigo imaging cytometer.

Production of proteins and purification.

  • Cells were infected by SeV at MOI of 0.1 for one hour, followed by replacement of medium with DMEM supplemented with 0.2 mg/mL TPCK-trypsin.
  • Supernatant including RBD-Fc were applied to Protein G Sepharose (Millipore Sigma, #GE17-0618-01) containing column (5ml Polypropylene Columns ;ThermoFisher, #29922), followed by wash and elution.
  • Authorities who make SARS-CoV-2 sequence data available in a timely manner via the GISAID initiative 66, 67 .
  • No statistically significant differences were detected between WT and VOC spikes in the size of GFP+ syncytia at any given time point (two-way ANOVA as above, 'ns' not indicated in graph).

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Figures (7)

Content maybe subject to copyright    Report

Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants
1
2
Satoshi Ikegame
1,#
, Mohammed N. A. Siddiquey
2,#
, Chuan-Tien Hung
1
, Griffin Haas
1
,
3
Luca Brambilla
1
, Kasopefoluwa Y. Oguntuyo
1
, Shreyas Kowdle
1
, Ariel Esteban Vilardo
3
,
4
Alexis Edelstein
3
, Claudia Perandones
3,✝
, Jeremy P. Kamil
2,✝
, and Benhur Lee
1,✝,
*
5
6
Affiliations.
7
1. Department of Microbiology at the Icahn School of Medicine at Mount Sinai, New
8
York, NY 10029, USA
9
2. Department of Microbiology and Immunology, Louisiana State University Health
10
Shreveport, Shreveport, LA 71103, USA.
11
3. National Administration of Laboratories and Health Institutes of Argentina (ANLIS) Dr.
12
Carlos G. Malbrán, Buenos Aires, Argentina
13
# These authors contributed equally to the study.
14
Senior authors
15
*
Correspondence to: Benhur Lee, benhur.lee@mssm.edu
16
17
Competing interests: B.L. and K.Y.O. are named inventors on a patent filed by the
18
Icahn School of Medicine for some of the materials used in this work. J.P.K. is a
19
consultant for BioNTech (advisory panel on coronavirus variants).
20
21
22
23
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted May 29, 2021. ; https://doi.org/10.1101/2021.03.31.21254660doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

2
ABSTRACT.
24
The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2
25
(SARS-CoV-2), has infected at least 120 million people since its identification as the
26
cause of a December 2019 viral pneumonia outbreak in Wuhan, China. Despite the
27
unprecedented pace of vaccine development, with six vaccines already in use
28
worldwide, the emergence of SARS-CoV-2 ‘variants of concern’ (VOC) across diverse
29
geographic locales suggests herd immunity may fail to eliminate the virus. All three
30
officially designated VOC carry Spike (S) polymorphisms thought to enable escape
31
from neutralizing antibodies elicited during initial waves of the pandemic. Here, we
32
characterize the biological consequences of the ensemble of S mutations present in
33
VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent
34
EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes
35
S from SARS coronavirus 2 in place of VSV-G, and coupled with a clonal HEK-293T
36
ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we
37
determined that only 1 out of 12 serum samples from a cohort of recipients of the
38
Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC
90
) of
39
rcVSV-CoV2-S: B.1.351 at full serum strength. The same set of sera efficiently
40
neutralized S from B.1.1.7 and showed only moderately reduced activity against S
41
carrying the E484K substitution alone. Taken together, our data suggest that control of
42
some emergent SARS-CoV-2 variants may benefit from updated vaccines.
43
44
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted May 29, 2021. ; https://doi.org/10.1101/2021.03.31.21254660doi: medRxiv preprint

3
INTRODUCTION.
45
In the 15 months since its emergence in late 2019
1
, SARS-CoV-2 has caused over 131
46
million confirmed COVID-19 cases worldwide, leading to at least 2.85 million deaths
2
.
47
SARS-CoV-2 is closely related to two other zoonotic betacoronaviruses, MERS-CoV
48
and SARS-CoV, that also cause life-threatening respiratory infections
3
.
49
This global health emergency has spurred the development of COVID-19 preventive
50
vaccines at an unprecedented pace. Six are already authorized for human use across
51
the globe
4–9
. These vaccines focus on the SARS-CoV-2 spike protein (S), due to its
52
critical roles in cell entry. Indeed, the presence of serum neutralizing antibodies
53
directed at S correlate strongly with protection against COVID-19
10,11
. Although these
54
six vaccines are efficacious, the recent emergence of novel SARS-CoV-2 variants has
55
reignited concerns that the pandemic may not be so easily brought under control.
56
In December 2020, the United Kingdom reported the sudden emergence of a novel
57
SARS-CoV-2 lineage, termed B.1.1.7 (501Y.V1, VOC 202012/01), which was
58
designated as the first SARS-CoV-2 variant of concern (VOC) . The lineage had rapidly
59
increased in prevalence since first being detected in November 2020
12
. Its genome
60
showed an unusually high number of non-synonymous substitutions and deletions,
61
including eight in the S gene, suggesting a substantial degree of host adaptation that
62
may have occurred during prolonged infection of an immunocompromised person
13
.
63
The B.1.1.7 lineage has now been shown to exhibit enhanced transmissibility
14
as well
64
as an increased case fatality rate
15,16
.
65
Soon afterwards, two additional SARS-CoV-2 VOC, B.1.351 and P.1, were
66
reported from S. Africa and Brazil, respectively, which each showed substantial escape
67
from neutralizing antibodies elicited by first wave pandemic viruses, leading to
68
documented cases of re-infection
1719
. The S genes of B.1.351 and P.1 viruses each
69
carry a number of mutations, but include three in the receptor binding domain (RBD)
70
that are particularly notable, the S: N501Y substitution, found in B.1.1.7, alongside
71
polymorphisms at positions 417 and 484, K417N/T and E484K. S: E484K had already
72
been identified in multiple independent laboratories to confer escape from
73
convalescent sera and monoclonal antibodies
2022
. As expected, the P.1 and B.1.351
74
variants escape or resist neutralization by first wave convalescent sera, as well as
75
antibodies elicited by COVID-19 vaccines
2327
.
76
Although the P.1 and B.1.351 lineages are dominant in Brazil and S. Africa,
77
unlike B.1.1.7 they have not increased greatly in number in the United States since
78
originally being detected here. In contrast, the E484K polymorphism is recurrently
79
emergent, and is found in a number of other lineages that are increasing in the U.S.
80
and other countries. For example, a B.1.526 sub-lineage carrying E484K in recent
81
weeks has expanded more rapidly than B.1.1.7
28,29
, which may be indicative of the
82
ability of S: E484K variants to penetrate herd immunity. The P.2 lineage, originally
83
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted May 29, 2021. ; https://doi.org/10.1101/2021.03.31.21254660doi: medRxiv preprint

4
detected in Rio de Janeiro, carries only the E484K mutation in the RBD and has spread
84
to other parts of South America, including Argentina
30
.
85
The six COVID-19 vaccines currently in use around the world employ different
86
strategies, and do not all incorporate the two proline substitutions that “lock” S into the
87
pre-fusion conformer. Vaccines that do not utilize pre-fusion “locked” S are expected
88
to produce lower levels of neutralizing antibodies, and hence may be less efficacious
89
against infection, even if they do protect against severe COVID-19
31,32
. Indeed, a two-
90
dose regimen of the AstraZeneca ChAdOx1 based vaccine, which does not use a
91
“locked” S, did not protect against mild-to-moderate COVID-19 in S. Africa, where
92
93% of COVID-19 cases in trial participants were caused by the B.1.351 variant
33
. Like
93
the AstraZeneca ChAdOx1 vaccine, the Sputnik V vaccine (Gam-COVID-Vac) is based
94
on adenovirus vectored expression of a native S sequence, rather than a pre-fusion
95
“locked” S
34
. Although the Sputnik V vaccine has a reported vaccine efficacy of 91.6%
96
in the interim analysis of Phase 3 trials held in Russia between Sept 7 and Nov 24,
97
2020, none of the VOC mentioned above nor independent lineages containing the
98
E484K mutation were prevalent in Russia during this time period. Since the Sputnik
99
vaccine is now in use not only in Russia, but also in countries like Argentina, Mexico,
100
and Hungary, where some of the VOC and emerging lineages bearing the E484K
101
mutation are more widespread, it is critical to assess the neutralizing activity of Sputnik
102
vaccine elicited antibody responses against these cognate VOC and mutant spikes.
103
This study characterizes the neutralization activity of sera from a dozen Sputnik
104
V vaccine recipients in Argentina. Our work was spurred by Argentina’s nascent
105
genomic surveillance efforts, which detected multiple independent lineages with S:
106
E484K (B.1.1.318 and P.2) and/or S: N501Y substitutions (B.1.1.7 and P.1) in common,
107
just as Argentina had started rolling out its vaccination campaign, which commenced
108
on Dec 29, 2020. Here, we generated isogenic replication-competent vesicular
109
stomatitis virus bearing the prevailing wild-type (WT=D614G) SARS-CoV-2 S (rcVSV-
110
CoV2-S), or the B.1.1.7, B.1.351 or E484K mutant S and used them in a robust virus
111
neutralization assay. Our results show that Sputnik V vaccine sera effectively
112
neutralized S: WT and S: B.1.1.7. viruses, albeit with highly variable titers. The same
113
sera, however, exhibited moderate and markedly reduced neutralization titers,
114
respectively, against S: E484K and S: B.1.351. Analyses of dose response curves
115
indicate that S: B.1.351 exhibits resistance to neutralizing sera in a manner that is
116
qualitatively different from the E484K mutant. Taken together, our data argue that
117
surveillance of the neutralizing activity elicited by vaccine sera will be necessary on an
118
ongoing basis. Viral neutralization assays can indicate which SARS-CoV-2 variants are
119
likely capable of transmission in the face of vaccine elicited immunity, and whether
120
updated vaccines will be needed to control their emergence and spread.
121
122
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted May 29, 2021. ; https://doi.org/10.1101/2021.03.31.21254660doi: medRxiv preprint

5
RESULTS.
123
Robust reverse genetics for generating replication-competent VSV expressing
124
SARS-CoV-2 Spike proteins.
125
Several groups have now generated replication-competent VSV expressing SARS-
126
CoV-2 spike in place of VSV-G (rcVSV-CoV2-S)
3537
,
38
. These rcVSV-CoV2-S can be
127
used in BSL-2 compatible virus neutralization assays (VNAs), which correlate very well
128
with VNAs using live SARS-CoV-2 (Spearman’s r > 0.9 across multiple studies). rcVSV-
129
CoV2-S has been assessed as a candidate vaccine
37
,
39
, and used in forward genetics
130
experiments to generate antibody escape mutants or perform comprehensive epitope
131
mapping studies
40
,
20
,
38
. Indeed, the now concerning E484K mutation, present in many
132
variants of concern (VOC), was identified as an antibody escape mutation using rcVSV-
133
CoV-2-S
20
,
38
.
134
However, many groups passage their rcVSV-CoV-2-S extensively in Vero cells after the
135
initial rescue, either to generate higher titer stocks and/or to remove confounding
136
components such as the vaccinia virus expressing T7-polymerase and/or transfected
137
VSV-G, both of which were deemed necessary for efficient rescue
38
. Serial passage of
138
rcVSV-CoV-2-S in Vero cells invariably leads to mutations in the S1/S2 furin cleavage
139
site, as well as truncations in the cytoplasmic tail of the S protein
39
. The latter
140
promotes S incorporation into VSV without compromising the conformational integrity
141
of the ectodomain, whereas the former is problematic when assessing the
142
neutralization sensitivity and structure-function phenotype of Spike VOC with multiple
143
mutations that likely have complex epistatic interactions.
144
To generate rcVSV-CoV2-S containing different variants or mutants on demand,
145
without the need for extensive passaging, we developed a robust reverse genetics
146
system and VNA which leverages the cell lines we previously developed for a
147
standardized SARS-CoV-2 VNA that correlates well with live virus neutralization
41
.
148
Salient improvements include the addition of a hammerhead ribozyme immediately
149
upstream of the 3’ leader sequence which cleaves in cis to give the exact 3’ termini,
150
the use of a codon-optimized T7-polymerase which alleviates the use of vaccinia-
151
driven T7-polymerase, and a highly permissive and transfectable 293T-
152
ACE2+TMPRSS2 clone (F8-2)
41
(Extended Data Fig S1). A 6-plasmid transfection into
153
F8-2 cells results in GFP+ cells 2-3 days post-transfection (dpt), which turn into foci of
154
syncytia by 4-5 dpt indicating virus replication and cell-to-cell spread (Fig. 1A). Transfer
155
of F8-2 cell supernatant into interferon-defective Vero-TMPRSS2 cells allowed for rapid
156
expansion of low-passage viral stocks that maintain only the engineered Spike
157
mutations. Clarified viral supernatants from Vero-TMPRSS2 cells were aliquoted,
158
sequenced verified, then titered on F8-2 cells to determine the linear range of response
159
(Fig. 1B).
160
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted May 29, 2021. ; https://doi.org/10.1101/2021.03.31.21254660doi: medRxiv preprint

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TL;DR: In this article, the authors investigated the infectivity and antigenicity of ten emerging SARS-CoV-2 variants-B.1.5, B.1,1.7, P.2(Zeta), P.429(Epsilon), B.525, B1.525 and B.526 in Calu-3 cells, and highlighted the importance of E484K mutation.
Abstract: Emerging mutations in SARS-CoV-2 cause several waves of COVID-19 pandemic. Here we investigate the infectivity and antigenicity of ten emerging SARS-CoV-2 variants-B.1.1.298, B.1.1.7(Alpha), B.1.351(Beta), P.1(Gamma), P.2(Zeta), B.1.429(Epsilon), B.1.525(Eta), B.1.526-1(Iota), B.1.526-2(Iota), B.1.1.318-and seven corresponding single amino acid mutations in the receptor-binding domain using SARS-CoV-2 pseudovirus. The results indicate that the pseudovirus of most of the SARS-CoV-2 variants (except B.1.1.298) display slightly increased infectivity in human and monkey cell lines, especially B.1.351, B.1.525 and B.1.526 in Calu-3 cells. The K417N/T, N501Y, or E484K-carrying variants exhibit significantly increased abilities to infect mouse ACE2-overexpressing cells. The activities of furin, TMPRSS2, and cathepsin L are increased against most of the variants. RBD amino acid mutations comprising K417T/N, L452R, Y453F, S477N, E484K, and N501Y cause significant immune escape from 11 of 13 monoclonal antibodies. However, the resistance to neutralization by convalescent serum or vaccines elicited serum is mainly caused by the E484K mutation. The convalescent serum from B.1.1.7- and B.1.351-infected patients neutralized the variants themselves better than other SARS-CoV-2 variants. Our study provides insights regarding therapeutic antibodies and vaccines, and highlights the importance of E484K mutation.

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    [...]

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Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...

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Journal ArticleDOI
13 Mar 2020-Science
TL;DR: The authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor, and test several published SARS-CoV RBD-specific monoclonal antibodies found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs.
Abstract: The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

7,324 citations


"Qualitatively distinct modes of Spu..." refers background in this paper

  • ...This modification locks the spike in a prefusion conformation and elicits higher titers of neutralizing antibodies (Pallesen et al., 2017; Wrapp et al., 2020)....

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Journal ArticleDOI
TL;DR: The mRNA-1273 vaccine as discussed by the authors is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.
Abstract: Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

2,721 citations

Journal ArticleDOI
TL;DR: This poster presents a poster presenting a poster presented at the 2016 International Conference of the Association for the Study of Viral Influenza and its Disruption in China, where it was presented for the first time.
Abstract: Yuelong Shu1, John McCauley2 1. WHO Collaborating Center for Reference and Research on Influenza, Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China 2. WHO Collaborating Centre for Reference and Research on Influenza, Crick Worldwide Influenza Centre, the Francis Crick Institute, London, United Kingdom

2,306 citations


"Qualitatively distinct modes of Spu..." refers methods in this paper

  • ...…all submitting authors and collecting authors on whose work this research is based, and to all researchers, clinicians, and public health authorities who make SARS-CoV-2 sequence data available in a timely manner via the GISAID initiative(Elbe and Buckland-Merrett, 2017; Shu and McCauley, 2017)....

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Q1. What have the authors contributed in "Neutralizing activity of sputnik v vaccine sera against sars-cov-2 variants" ?

11 3. National Administration of Laboratories and Health Institutes of Argentina ( ANLIS ) Dr. 12 Carlos G. Malbrán, Buenos Aires, Argentina 13 # These authors contributed equally to the study. Edu 16 17 Competing interests: B. L. and K. Y. O. are named inventors on a patent filed by the 18 Icahn School of Medicine for some of the materials used in this work. It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.