scholarly journals Cross-neutralizing activity against SARS-CoV-2 variants in COVID-19 patients: Comparison of four waves of the pandemic in Japan

2021 ◽  
Author(s):  
Koichi Furukawa ◽  
Lidya Handayani Tjan ◽  
Silvia Sutandhio ◽  
Yukiya Kurahashi ◽  
Sachiyo Iwata ◽  
...  
Keyword(s):  
Conformational Change ◽  
Spike Protein ◽  
Lower Activity ◽  
Immune Recognition ◽  
Similar Activity ◽  
Neutralizing Activity ◽  
Novel Variants ◽  
The Cross ◽  
Spread Of Infection

Abstract Background In March 2021, Japan is facing a 4th wave of SARS-CoV-2 infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but is not firmly established. Methods We investigated the neutralizing potency of 81 COVID-19 patients' sera from the 1st–4th waves of pandemic against SARS-CoV-2 D614G, B.1.1.7, P.1, and B.1.351 variants using their authentic viruses. Results Most sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the 4th wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The sera-neutralizing activity in less-severe patients was lower than that of more-severe patients for all variants. Conclusions The cross-neutralizing activity of convalescent sera was effective against all variants but was potentially weaker for B.1.351. The high neutralizing activity specific for B.1.1.7 in the 4th wave suggests that the mutations in the virus might cause conformational change of its spike protein, which affects immune recognition for D614G. Our results indicate that individuals who recover from COVID-19 could be protected from the severity caused by infection with newly emerging variants.

scholarly journals Cross-neutralizing activity against SARS-CoV-2 variants in COVID-19 patients: Comparison of four waves of the pandemic in Japan

2021 ◽  
Author(s):  
Koichi Furukawa ◽  
Lidya Handayani Tjan ◽  
Silvia Sutandhio ◽  
Yukiya Kurahashi ◽  
Sachiyo Iwata ◽  
...  
Keyword(s):  
Lower Activity ◽  
Similar Activity ◽  
Neutralizing Activity ◽  
Novel Variants ◽  
The Cross ◽  
Spread Of Infection

In March 2021, Japan is facing a 4th wave of SARS-CoV-2 infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but is not firmly established. We investigated the neutralizing potency of 81 COVID-19 patients' sera from 4 waves of pandemic against SARS-CoV-2 variants using their authentic viruses. Most sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the 4th wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The cross-neutralizing activity of convalescent sera was effective against all variants but was potentially weaker for B.1.351.

scholarly journals The Cross-Neutralizing Activity of Enterovirus 71 Subgenotype C4 Vaccines in Healthy Chinese Infants and Children

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e79599 ◽  
Author(s):  
Qunying Mao ◽  
Tong Cheng ◽  
Fengcai Zhu ◽  
Jingxin Li ◽  
Yiping Wang ◽  
...  
Keyword(s):  
Enterovirus 71 ◽  
Infants And Children ◽  
Neutralizing Activity ◽  
Healthy Chinese ◽  
The Cross

scholarly journals Previous Infection Combined with Vaccination Produces Neutralizing Antibodies With Potency Against SARS-CoV-2 Variants

2021 ◽  
Author(s):  
F Javier Ibarrondo ◽  
Christian Hofmann ◽  
Ayub Ali ◽  
Paul Ayoub ◽  
Donald B Kohn ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Neutralizing Antibodies ◽  
Spike Protein ◽  
Original Sequence ◽  
Neutralizing Activity ◽  
Previous Infection ◽  
Protein Mutations ◽  
Antigenic Exposure ◽  
Prior Infection ◽  
Spike Sequence

SARS-CoV-2 continues to evolve in humans. Spike protein mutations increase transmission and potentially evade antibodies raised against the original sequence used in current vaccines. Our evaluation of serum neutralizing activity in both persons soon after SARS-CoV-2 infection (in April 2020 or earlier) or vaccination without prior infection confirmed that common spike mutations can reduce antibody antiviral activity. However, when the persons with prior infection were subsequently vaccinated, their antibodies attained an apparent biologic ceiling of neutralizing potency against all tested variants, equivalent to the original spike sequence. These findings indicate that additional antigenic exposure further improves antibody efficacy against variants.

scholarly journals Antibody Cocktail Exhibits Broad Neutralization against SARS-CoV-2 and SARS-CoV-2 variants

2021 ◽  
Author(s):  
Yuanyuan Qu ◽  
Xueyan Zhang ◽  
Meiyu Wang ◽  
Lina Sun ◽  
Yongzhong Jiang ◽  
...  
Keyword(s):  
Immune Escape ◽  
Conformational Epitope ◽  
Viral Escape ◽  
Angiotensin Converting Enzyme 2 ◽  
Neutralizing Activity ◽  
High Affinity ◽  
Phage Display Libraries ◽  
Novel Variants ◽  
Antibody Phage ◽  
Antibody Phage Display

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446 - S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, F61 and H121 exhibited efficient neutralizing activity against variants B.1.1.7 and B.1.351, those showed immune escape. Efficient neutralization of F61 and H121 against multiple mutations within RBD revealed a broad neutralizing activity against SARS-CoV-2 variants, which mitigated the risk of viral escape. Our findings defined the basis of therapeutic cocktails of F61 and H121 with broad neutralization and delivered a guideline for the current and future vaccine design, therapeutic antibody development, and antigen diagnosis of SARS-CoV-2 and its novel variants.

scholarly journals The SARS-CoV-2 infection in Thailand: analysis of spike variants complemented by protein structure insights

2022 ◽  
Author(s):  
Sirawit Ittisoponpisan ◽  
Shalip Yahangkiakan ◽  
Michael J.E. Sternberg ◽  
Alessia David
Keyword(s):  
Structural Change ◽  
Protein Structure ◽  
Genetic Variations ◽  
Spike Protein ◽  
Common Variants ◽  
Novel Variants ◽  
Prevalent Strain ◽  
Global Concern

Thailand was the first country outside China to officially report COVID-19 cases. Despite the strict regulations for international arrivals, up until February 2021, Thailand had been hit by two major outbreaks. With a large number of SARS-CoV-2 sequences collected from patients, the effects of many genetic variations, especially those unique to Thai strains, are yet to be elucidated. In this study, we analysed 439,197 sequences of the SARS-CoV-2 spike protein collected from NCBI and GISAID databases. 595 sequences were from Thailand and contained 52 variants, of which 6 had not been observed outside Thailand (p.T51N, p.P57T, p.I68R, p.S205T, p.K278T, p.G832C). These variants were not predicted to be of concern. We demonstrate that the p.D614G, although already present during the first Thai outbreak, became the prevalent strain during the second outbreak, similarly to what was described in other countries. Moreover, we show that the most common variants detected in Thailand (p.A829T, p.S459F and p.S939F) do not appear to cause any major structural change to the spike trimer or the spike-ACE2 interaction. Among the variants identified in Thailand was p.N501T. This variant, which involves an asparagine critical for spike-ACE2 binding, was not predicted to increase SARS-CoV-2 binding, thus in contrast to the variant of global concern p.N501Y. In conclusion, novel variants identified in Thailand are unlikely to increase the fitness of SARS-CoV-2. The insights obtained from this study could aid SARS-CoV-2 variants prioritisations and help molecular biologists and virologists working on strain surveillance.

scholarly journals Weak Cross-Lineage Neutralization by Anti SARS-CoV-2 Spike Antibodies after Natural Infection or Vaccination Is Rescued by Repeated Immunological Stimulation

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1124
Author(s):  
Sara Caucci ◽  
Benedetta Corvaro ◽  
Sofia Maria Luigia Tiano ◽  
Anna Valenza ◽  
Roberta Longo ◽  
...  
Keyword(s):  
Single Dose ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Natural Immunity ◽  
Anamnestic Response ◽  
Neutralizing Activity ◽  
Immunological Markers ◽  
The Cross ◽  
One Year

After over one year of evolution, through billions of infections in humans, SARS-CoV-2 has evolved into a score of slightly divergent lineages. A few different amino acids in the spike proteins of these lineages can hamper both natural immunity against reinfection, and vaccine efficacy. In this study, the in vitro neutralizing potency of sera from convalescent COVID-19 patients and vaccinated subjects was analyzed against six different SARS-CoV-2 lineages, including the latest B.1.617.2 (or Delta variant), in order to assess the cross-neutralization by anti-spike antibodies. After both single dose vaccination, or natural infection, the neutralizing activity was low and fully effective only against the original lineage, while a double dose or a single dose of vaccine, even one year after natural infection, boosted the cross-neutralizing activity against different lineages. Neither binding, nor the neutralizing activity of sera after vaccination, could predict vaccine failure, underlining the need for additional immunological markers. This study points at the importance of the anamnestic response and repeated vaccine stimulations to elicit a reasonable cross-lineage neutralizing antibody response.

scholarly journals Changes in Spike Protein Antibody Titer Over 90 Days after the Second Dose of SARS- CoV-2 Vaccine in Japanese Dialysis Patients

2021 ◽  
Author(s):  
Haruki Wakai ◽  
Natsumi Abe ◽  
Touno Tokuda ◽  
Rika Yamanaka ◽  
Satoshi Ebihara ◽  
...  
Keyword(s):  
Antibody Titer ◽  
Messenger Rna ◽  
Vaccine Dose ◽  
Spike Protein ◽  
Dialysis Patients ◽  
Protein Levels ◽  
The Status ◽  
Antibody Titers ◽  
Baseline Characteristics ◽  
Spread Of Infection

Abstract Objectives There is no report on antibody titers after vaccination against SARS-CoV-2 in Japanese dialysis patients. As dialysis is different between Japan and other countries, changes in antibody titers were examined. Methods Baseline characteristics and anti-spike protein antibody titers (Roche) over 90 days after administration of the BNT162b2 messenger RNA vaccine were investigated in dialysis patients. Results The maximum anti-spike protein antibody titer after the second dose was 737.9 (326.8 to 1143.4) and was reached at 19 (17 to 24.3) days after the second dose. Antibody titers decreased over time, with titers of 770 (316.4 to 1089) at 15 days, 385 (203 to 689.7) at 30 days, 253.5 (138 to 423) at 60 days, and 208 (107 to 375) at 90 days after the second dose. When an antibody titer of 137.052 U/mL was assumed to be a measure related to breakthrough infection, the proportion of subjects with antibody titers exceeding this level was 90.1％ at 15 days, 85.3% at 30 days, 75.0% at 60 days, and 65.4% at 90 days after the second dose. When a decrease in antibody titers below the assumed breakthrough level was defined as an event, subjects with a pre-dialysis albumin ≥ 3.5 were significantly less likely to experience an event than subjects with a pre-dialysis albumin < 3.5. In addition, this study suggests that the presence of anti-spike protein levels ≥ 313 at 30 days after the second vaccine dose might be a factor in maintaining antibody titers exceeding the assumed breakthrough level at 90 days after the second dose. Conclusions The maximum antibody titers and the antibody titers at 90 days after the second vaccine dose in Japanese dialysis patients were approximately 30% of those in non-dialysis individuals reported otherwise, it was similar to those in dialysis patients in other countries. Whether an additional vaccine dose is needed should be determined based on indicators serving as factors in maintaining antibody titers as well as the status of the spread of infection.

scholarly journals Age-Dependent Reduction in Neutralization against Alpha and Beta Variants of BNT162b2 SARS-CoV-2 Vaccine-Induced Immunity

2021 ◽  
Author(s):  
Hitoshi Kawasuji ◽  
Yoshitomo Morinaga ◽  
Hideki Tani ◽  
Yumiko Saga ◽  
Makito Kaneda ◽  
...  
Keyword(s):  
Age Groups ◽  
Older Age ◽  
Spike Protein ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Neutralizing Activity ◽  
Age Dependent ◽  
Induced Immunity

Since mRNA vaccines utilize wild-type SARS-CoV-2 spike protein as an antigen, there are potential concerns about acquiring immunity to variants of this virus. The neutralizing activity in BNT162b2-vaccinated individuals was higher against the wild-type virus than against its variants; this effect was more apparent in older age groups.

scholarly journals Cross-Neutralizing Activity of Monoclonal Antibodies Against N501Y Mutant Strain of SARS-CoV-2

2020 ◽  
Vol 9 (4) ◽  
pp. 41-45
Author(s):  
Ruxia Ding ◽  
Haixin Wang ◽  
Yi Yang ◽  
Liangshu Xie ◽  
Li Zhang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Mutant Strain ◽  
Wild Type Strain ◽  
Neutralization Assay ◽  
Spike Protein ◽  
Wild Type ◽  
Neutralizing Activity ◽  
Theory Result ◽  
Global Concern ◽  
The Uk

The dominant N501Y mutation in the spike protein that SARS-CoV-2 virus uses to bind to the human ACE2 receptor were found in the UK, which has aroused global concern and worried. Mutations in spike protein may, in theory, result in more infectious and spreading more easily. In order to evaluate the broad-spectrum protective effect of the monoclonal antibodies(mAbs), we compared the neutralization activities of six prepared mAbs against SARS-CoV-2 with pseudovirus neutralization assay. Only one of them showed a decrease of 6 folds in neutralizing activity to N501Y mutant strain, compared with the wild type strain. We should continue to monitor emergence of new variants in different regions to study their infectivity and neutralization effect.

scholarly journals Discovery of human ACE2 variants with altered recognition by the SARS-CoV-2 spike protein

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251585
Author(s):  
Pete Heinzelman ◽  
Philip A. Romero
Keyword(s):  
Clinical Trial ◽  
Genetic Variants ◽  
Trial Design ◽  
Clinical Trial Design ◽  
Spike Protein ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Novel Variants ◽  
The Future ◽  
Fundamental Research

Understanding how human ACE2 genetic variants differ in their recognition by SARS-CoV-2 can facilitate the leveraging of ACE2 as an axis for treating and preventing COVID-19. In this work, we experimentally interrogate thousands of ACE2 mutants to identify over one hundred human single-nucleotide variants (SNVs) that are likely to have altered recognition by the virus, and make the complementary discovery that ACE2 residues distant from the spike interface influence the ACE2-spike interaction. These findings illuminate new links between ACE2 sequence and spike recognition, and could find substantial utility in further fundamental research that augments epidemiological analyses and clinical trial design in the contexts of both existing strains of SARS-CoV-2 and novel variants that may arise in the future.

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