Neutralization of SARS-CoV-2 Omicron pseudovirus by BNT162b2 vaccine-elicited human sera

A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage, B.1.1.529, was recently detected in Botswana and South Africa and is now circulating globally. Just two days after it was first reported to the World Health Organization (WHO), this strain was classified as a variant of concern (VOC) and named Omicron. Omicron has an unusually large number of mutations, including up to 39 amino acid modifications in the spike (S) protein, raising concerns that its recognition by neutralizing antibodies from convalescent and vaccinated individuals may be severely compromised. In this study, we tested pseudoviruses carrying the SARS-CoV-2 spike glycoproteins of either the Wuhan reference strain, the Beta, the Delta or the Omicron variants of concern with sera of 51 participants that received two doses or a third dose (≥6 months after dose 2) of the mRNA-based COVID-19 vaccine BNT162b2. Immune sera from individuals who received two doses of BNT162b2 had more than 22-fold reduced neutralizing titers against the Omicron as compared to the Wuhan pseudovirus. One month after a third dose of BNT162b2, the neutralization titer against Omicron was increased 23-fold compared to two doses and antibody titers were similar to those observed against the Wuhan pseudovirus after two doses of BNT162b2. These data suggest that a third dose of BNT162b2 may protect against Omicron-mediated COVID-19, but further analyses of longer-term antibody persistence and real-world effectiveness data are needed.

Download Full-text

Low neutralizing antibody titers against the Mu variant of SARS-CoV-2 in BNT162b2 vaccinated individuals

10.1101/2021.11.19.21266552 ◽

2021 ◽

Author(s):

Diego Alejandro Alvarez-Diaz ◽

Ana L Munoz ◽

Pilar Tavera-Rodriguez ◽

Maria T Herrera-Sepulveda ◽

Hector A Ruiz-Moreno ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Spike Protein ◽

World Health ◽

The World ◽

Need To Evaluate ◽

Surveillance Programs ◽

Antibody Titers ◽

Epidemiological Impact ◽

Health Organization

Background Global surveillance programs for the virus that causes COVID-19 are showing the emergence of variants with mutations in the Spike protein, including the Mu variant, recently declared as a Variant of Interest (VOI) by the World Health Organization. Because these types of variants can be more infectious or less susceptible to antiviral treatments and vaccine-induced antibodies. Objectives To evaluate the sensitivity of the Mu variant (B.1.621) to neutralizing antibodies induced by the BNT162b2 vaccine. Study design Three of the most predominant SARS-CoV-2 variants in Colombia during the epidemiological peaks of 2021 were isolated. Microneutralization assays were performed by incubating 120 TCDI50 of each SARS-CoV-2 isolate with five 2-fold serial dilutions of sera from 14 BNT162b2 vaccinated volunteers. The MN50 titer was calculated by the Reed-Muench formula Results The three isolated variants were Mu, a Variant of Interest (VOI), Gamma, a variant of concern (VOC), and B.1.111 that lacks genetic markers associated with greater virulence. At the end of August, the Mu and Gamma variants were widely distributed in Colombia. Mu was predominant (49%), followed by Gamma (25%). In contrast, B.1.111 became almost undetectable. The evaluation of neutralizing antibodies suggests that patients vaccinated with BNT162-2 generate neutralizing antibody titers against the Mu variant at significantly lower concentrations relative to B.1.111 and Gamma. Conclusions This study shows the importance of continuing with surveillance programs of emerging variants as well as the need to evaluate the neutralizing antibody response induced by other vaccines circulating in the country against Mu and other variants with high epidemiological impact.

Download Full-text

Antibody titers measured by commercial assays are correlated with neutralizing antibody titers calibrated by international standards

10.1101/2021.07.16.21260618 ◽

2021 ◽

Author(s):

Yu-An Kung ◽

Chung-Guei Huang ◽

Sheng-Yu Huang ◽

Kuan-Ting Liu ◽

Peng-Nien Huang ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Vaccine Development ◽

Geometric Mean ◽

Neutralizing Antibody ◽

Diagnostic Techniques ◽

International Standards ◽

World Health ◽

Serum Samples ◽

Antibody Titers ◽

Health Organization

The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.

Download Full-text

Neutralization of SARS-CoV-2 Omicron variant by sera from BNT162b2 or Coronavac vaccine recipients

10.1101/2021.12.13.21267668 ◽

2021 ◽

Author(s):

Lu Lu ◽

Bobo Mok ◽

Linlei Chen ◽

Jacky Chan ◽

Owen Tsang ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Geometric Mean ◽

Neutralizing Antibody ◽

World Health ◽

Whole Genome Sequence ◽

Live Virus ◽

Significant Difference ◽

Antibody Titers ◽

Ancestral Virus ◽

Health Organization

Background The SARS-CoV-2 Omicron variant, designated as a Variant of Concern(VOC) by the World Health Organization, carries numerous spike protein mutations which have been found to evade neutralizing antibodies elicited by COVID-19 vaccines. The susceptibility of Omicron variant by vaccine-induced neutralizing antibodies are urgently needed for risk assessment. Methods Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the Omicron, Delta and Beta variants to sera from 25 BNT162b2 and 25 Coronavac vaccine recipients was determined using a live virus microneutralization assay. Results The Omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains in GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the Omicron variant HKU691 and HKU344-R346K, respectively, while none of the Coronavac recipients had detectable neutralizing antibody titer against either Omicron isolates. For BNT162b2 recipients, the geometric mean neutralization antibody titers(GMT) of the Omicron variant isolates(5.43 and 6.42) were 35.7-39.9-fold lower than that of the ancestral virus(229.4), and the GMT of both omicron isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMT between HKU691 and HKU344-R346K. Conclusions Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the Omicron variant may be associated with lower COVID-19 vaccine effectiveness.

Download Full-text

An Overview on Lambda, Epsilon, Kappa, Iota and Zeta Variants of Covid-19 and its Probability to Merge with Delta & Delta Plus, why it is a Concern

Biointerface Research in Applied Chemistry ◽

10.33263/briac125.68956914 ◽

2021 ◽

Vol 12 (5) ◽

pp. 6895-6914

Keyword(s):

World Health Organization ◽

Neutralizing Antibodies ◽

Spike Protein ◽

World Health ◽

South American ◽

Infected Person ◽

High Prevalence ◽

The World ◽

Health Organization

COVID-19 is caused by the virus SARS-CoV-2 that belongs to the Corona groups. The subgroups of the coronavirus families are α, β, γ, and δ coronavirus. On June 15, 2021, the string λ of SARS-CoV-2 was evaluated as a variant of interest via the World Health Organization. This string has a high prevalence in some parts of South American countries, but it occurred only occasionally in Brazil. This study confirms that mutations in the λ -spike protein can be destroyed the neutralizing antibodies and increase infectivity. Coronaviruses such as SARS-CoV-2 have an evolutionary superpower called “recombination” which permits the mixing of their genomes into novel combinations. Unlike regular mutation, which precedes slowly one change at a time, recombination can produce whole changes in a coronavirus genome. Although right now, δ-variant is a concern, a mixing of λ with other variants such as δ-variant is much more of a concern compared to alone variants. There is another item: the recombination can arise within the sample after it was taken from the infected person, not while it was inside their body.

Download Full-text

Key features of tests for detection of SARS-CoV2 antibodies

Medical alphabet ◽

10.33667/2078-5631-2021-13-13-17 ◽

2021 ◽

pp. 13-17

Author(s):

V. S. Berestovskaya ◽

T. V. Vavilova ◽

A. V. Gubanova ◽

N. Yu. Chernysh

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

World Health ◽

Receptor Binding Domain ◽

Test Format ◽

Specific Antibodies ◽

The World ◽

Quantitative Results ◽

Key Features ◽

Health Organization

On March 11, 2020, the World Health Organization recognized the outbreak of the disease COVID-19 (Coronavirus Disease 2019) and the spread of the new coronavirus (SARS-CoV-2), which caused this disease, as a pandemic. The SARS-CoV-2 virus stimulates the production of antigen-specific antibodies for which commercial tests have been developed. The issue of diagnosing antibodies to SARS-CoV-2 became especially acute together with the beginning of mass vaccination of the population. Due to the fact that the reading of the result depends on the test format, it is necessary to understand how the antigenic target, the composition of the immunoglobulins and the way of expressing the result affect its interpretation. When analyzing the literature, it was found that with COVID-19, antibodies to the nucleocapsid antigen of SARS-CoV-2 can be detected somewhat earlier than antibodies to the spike antigen; virus-neutralizing antibodies are directed to the receptor-binding domain, seroconversion of immunoglobulins M and G begins simultaneously, and tests for total antibodies are potentially more sensitive due to the ability to capture antibodies with various features of the immune response. The problem of incomparability of quantitative results obtained on different systems is also noted. These factors must be taken into account when choosing a test for detecting antibodies to SARS-CoV-2, which will adequately solve a specific clinical and epidemiological problem.

Download Full-text

Timeline of SARS-CoV-2 Spread in Italy: Results from an Independent Serological Retesting

Viruses ◽

10.3390/v14010061 ◽

2021 ◽

Vol 14 (1) ◽

pp. 61

Author(s):

Emanuele Montomoli ◽

Giovanni Apolone ◽

Alessandro Manenti ◽

Mattia Boeri ◽

Paola Suatoni ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralization Test ◽

World Health ◽

Independent Evaluation ◽

Igg Binding ◽

Short Period ◽

The World ◽

One Year ◽

Health Organization ◽

Control Samples

The massive emergence of COVID-19 cases in the first phase of pandemic within an extremely short period of time suggest that an undetected earlier circulation of SARS-CoV-2 might have occurred. Given the importance of this evidence, an independent evaluation was recommended by the World Health Organization (WHO) to test a subset of samples selected on the level of positivity in ELISA assays (positive, low positive, negative) detected in our previous study of prepandemic samples collected in Italy. SARS-CoV-2 antibodies were blindly retested by two independent centers in 29 blood samples collected in the prepandemic period in Italy, 29 samples collected one year before and 11 COVID-19 control samples. The methodologies used included IgG-RBD/IgM-RBD ELISA assays, a qualitative micro-neutralization CPE-based assay, a multiplex IgG protein array, an ELISA IgM kit (Wantai), and a plaque-reduction neutralization test. The results suggest the presence of SARS-CoV-2 antibodies in some samples collected in the prepandemic period, with the oldest samples found to be positive for IgM by both laboratories collected on 10 October 2019 (Lombardy), 11 November 2019 (Lombardy) and 5 February 2020 (Lazio), the latter with neutralizing antibodies. The detection of IgM and/or IgG binding and neutralizing antibodies was strongly dependent on the different serological assays and thresholds employed, and they were not detected in control samples collected one year before. These findings, although gathered in a small and selected set of samples, highlight the importance of harmonizing serological assays for testing the spread of the SARS-CoV-2 virus and may contribute to a better understanding of future virus dynamics.

Download Full-text

Genome Sequence of a Candidate World Health Organization Reference Strain of Zika Virus for Nucleic Acid Testing

Genome Announcements ◽

10.1128/genomea.00917-16 ◽

2016 ◽

Vol 4 (5) ◽

Cited By ~ 17

Author(s):

Jan-Hendrik Trösemeier ◽

Didier Musso ◽

Johannes Blümel ◽

Julien Thézé ◽

Oliver G. Pybus ◽

...

Keyword(s):

Nucleic Acid ◽

World Health Organization ◽

Zika Virus ◽

Reference Strain ◽

Nucleic Acid Amplification ◽

World Health ◽

Nucleic Acid Testing ◽

The World ◽

Health Organization ◽

Detection And Quantification

We report here the sequence of a candidate reference strain of Zika virus (ZIKV) developed on behalf of the World Health Organization (WHO). The ZIKV reference strain is intended for use in nucleic acid amplification (NAT)-based assays for the detection and quantification of ZIKV RNA.

Download Full-text

Development of Coronavirus Treatments Using Neutralizing Antibodies

Microorganisms ◽

10.3390/microorganisms9010165 ◽

2021 ◽

Vol 9 (1) ◽

pp. 165

Author(s):

Saman Fouladirad ◽

Horacio Bach

Keyword(s):

Neutralizing Antibodies ◽

Invasive Mechanical Ventilation ◽

Intravenous Immunoglobulins ◽

World Health ◽

The Novel ◽

New Approach ◽

The World ◽

Novel Coronavirus ◽

Health Organization

The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, was first reported in December 2019 in Wuhan, Hubei province, China. This virus has led to 61.8 million cases worldwide being reported as of December 1st, 2020. Currently, there are no definite approved therapies endorsed by the World Health Organization for COVID-19, focusing only on supportive care. Treatment centers around symptom management, including oxygen therapy or invasive mechanical ventilation. Immunotherapy has the potential to play a role in the treatment of SARS-CoV-2. Monoclonal antibodies (mAbs), in particular, is a relatively new approach in the world of infectious diseases and has the benefit of overcoming challenges with serum therapy and intravenous immunoglobulins preparations. Here, we reviewed the articles published in PubMed with the purpose of summarizing the currently available evidence for the use of neutralizing antibodies as a potential treatment for coronaviruses. Studies reporting in vivo results were summarized and analyzed. Despite promising data from some studies, none of them progressed to clinical trials. It is expected that neutralizing antibodies might offer an alternative for COVID-19 treatment. Thus, there is a need for randomized trials to understand the potential use of this treatment.

Download Full-text