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

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.

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

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.

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

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.

scholarly journals 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

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.

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

2021 ◽  
Author(s):  
Alexander Muik ◽  
Bonny Gaby Lui ◽  
Ann-Kathrin Wallisch ◽  
Maren Bacher ◽  
Julia Muehl ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Reference Strain ◽  
World Health ◽  
Neutralization Titer ◽  
Antibody Persistence ◽  
The World ◽  
Human Sera ◽  
Antibody Titers ◽  
Health Organization ◽  
Effectiveness Data

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.

scholarly journals Improved neutralization of the SARS-CoV-2 Omicron variant after Pfizer-BioNTech BNT162b2 COVID-19 vaccine boosting

2021 ◽  
Author(s):  
Kerri Basile ◽  
Rebecca J Rockett ◽  
Kenneth McPhie ◽  
Michael Fennell ◽  
Jessica Johnson-Mackinnon ◽  
...  
Keyword(s):  
World Health Organization ◽  
Receptor Binding ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
World Health ◽  
Receptor Binding Domain ◽  
Limited Ability ◽  
The World ◽  
Antibody Titres ◽  
Health Organization

In late November 2021, the World Health Organization declared the SARS-CoV-2 lineage B.1.1.529 the fifth variant of concern, Omicron. This variant has acquired 15 mutations in the receptor binding domain of the spike protein, raising concerns that Omicron could evade naturally acquired and vaccine-derived immunity. We utilized an authentic virus, multicycle neutralisation assay to demonstrate that sera collected 1, 3, and 6 months post-two doses of Pfizer-BioNTech BNT162b2 has a limited ability to neutralise SARS-CoV-2. However, four weeks after a third dose, neutralizing antibody titres are boosted. Despite this increase, neutralising antibody titres are reduced 4-fold for Omicron compared to lineage A.2.2 SARS-CoV-2.

scholarly journals Severe Acute Respiratory Syndrome-Associated Coronavirus Vaccines Formulated with Delta Inulin Adjuvants Provide Enhanced Protection while Ameliorating Lung Eosinophilic Immunopathology

2014 ◽  
Vol 89 (6) ◽  
pp. 2995-3007 ◽  
Author(s):  
Yoshikazu Honda-Okubo ◽  
Dale Barnard ◽  
Chun Hao Ong ◽  
Bi-Hung Peng ◽  
Chien-Te Kent Tseng ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
Case Fatality ◽  
Neutralizing Antibody ◽  
The Elderly ◽  
Spike Protein ◽  
Interleukin 4 ◽  
Unique Problem ◽  
Antibody Titers ◽  
Ifn Γ

ABSTRACTAlthough the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) epidemic was controlled by nonvaccine measures, coronaviruses remain a major threat to human health. The design of optimal coronavirus vaccines therefore remains a priority. Such vaccines present major challenges: coronavirus immunity often wanes rapidly, individuals needing to be protected include the elderly, and vaccines may exacerbate rather than prevent coronavirus lung immunopathology. To address these issues, we compared in a murine model a range of recombinant spike protein or inactivated whole-virus vaccine candidates alone or adjuvanted with either alum, CpG, or Advax, a new delta inulin-based polysaccharide adjuvant. While all vaccines protected against lethal infection, addition of adjuvant significantly increased serum neutralizing-antibody titers and reduced lung virus titers on day 3 postchallenge. Whereas unadjuvanted or alum-formulated vaccines were associated with significantly increased lung eosinophilic immunopathology on day 6 postchallenge, this was not seen in mice immunized with vaccines formulated with delta inulin adjuvant. Protection against eosinophilic immunopathology by vaccines containing delta inulin adjuvants correlated better with enhanced T-cell gamma interferon (IFN-γ) recall responses rather than reduced interleukin-4 (IL-4) responses, suggesting that immunopathology predominantly reflects an inadequate vaccine-induced Th1 response. This study highlights the critical importance for development of effective and safe coronavirus vaccines of selection of adjuvants based on the ability to induce durable IFN-γ responses.IMPORTANCECoronaviruses such as SARS-CoV and Middle East respiratory syndrome-associated coronavirus (MERS-CoV) cause high case fatality rates and remain major human public health threats, creating a need for effective vaccines. While coronavirus antigens that induce protective neutralizing antibodies have been identified, coronavirus vaccines present a unique problem in that immunized individuals when infected by virus can develop lung eosinophilic pathology, a problem that is further exacerbated by the formulation of SARS-CoV vaccines with alum adjuvants. This study shows that formulation of SARS-CoV spike protein or inactivated whole-virus vaccines with novel delta inulin-based polysaccharide adjuvants enhances neutralizing-antibody titers and protection against clinical disease but at the same time also protects against development of lung eosinophilic immunopathology. It also shows that immunity achieved with delta inulin adjuvants is long-lived, thereby overcoming the natural tendency for rapidly waning coronavirus immunity. Thus, delta inulin adjuvants may offer a unique ability to develop safer and more effective coronavirus vaccines.

scholarly journals The global population of SARS-CoV-2 is composed of six major subtypes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ivair José Morais ◽  
Richard Costa Polveiro ◽  
Gabriel Medeiros Souza ◽  
Daniel Inserra Bortolin ◽  
Flávio Tetsuo Sassaki ◽  
...  
Keyword(s):  
Genetic Structure ◽  
First Century ◽  
Spike Protein ◽  
World Health ◽  
Clustering Methods ◽  
Confounding Effect ◽  
Robust Clustering ◽  
The World ◽  
Health Organization ◽  
Global Population

Abstract The World Health Organization characterized COVID-19 as a pandemic in March 2020, the second pandemic of the twenty-first century. Expanding virus populations, such as that of SARS-CoV-2, accumulate a number of narrowly shared polymorphisms, imposing a confounding effect on traditional clustering methods. In this context, approaches that reduce the complexity of the sequence space occupied by the SARS-CoV-2 population are necessary for robust clustering. Here, we propose subdividing the global SARS-CoV-2 population into six well-defined subtypes and 10 poorly represented genotypes named tentative subtypes by focusing on the widely shared polymorphisms in nonstructural (nsp3, nsp4, nsp6, nsp12, nsp13 and nsp14) cistrons and structural (spike and nucleocapsid) and accessory (ORF8) genes. The six subtypes and the additional genotypes showed amino acid replacements that might have phenotypic implications. Notably, three mutations (one of them in the Spike protein) were responsible for the geographical segregation of subtypes. We hypothesize that the virus subtypes detected in this study are records of the early stages of SARS-CoV-2 diversification that were randomly sampled to compose the virus populations around the world. The genetic structure determined for the SARS-CoV-2 population provides substantial guidelines for maximizing the effectiveness of trials for testing candidate vaccines or drugs.

scholarly journals Mutations that confer resistance to broadly-neutralizing antibodies define HIV-1 variants of transmitting mothers from that of non-transmitting mothers

2021 ◽  
Author(s):  
Amit Kumar ◽  
Elena E Giorgi ◽  
Joshua J Tu ◽  
David R Martinez ◽  
Joshua Eudailey ◽  
...  
Keyword(s):  
Vertical Transmission ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Maternal Plasma ◽  
Pediatric Hiv ◽  
World Health ◽  
Autologous Plasma ◽  
Maternal Risk ◽  
Health Organization ◽  
Hiv 1

Despite considerable reduction of mother-to-child transmission (MTCT) of HIV through use of maternal and infant antiretroviral therapy (ART), over 150,000 infants continue to become infected with HIV annually, falling far short of the World Health Organization goal of reaching <20,000 annual pediatric HIV cases worldwide by 2020. Prior to the widespread use of ART in the setting of pregnancy, over half of infants born to HIV-infected mothers were protected against HIV acquisition. Yet, the role of maternal immune factors in this protection against vertical transmission is still unclear, hampering the development of synergistic strategies to further reduce MTCT. It has been established that infant transmitted/founder (T/F) viruses are often resistant to maternal plasma, yet it is unknown if the neutralization resistance profile of circulating viruses predicts the maternal risk of transmission to her infant. In this study, we amplified HIV-1 envelope genes (env) by single genome amplification and produced representative Env variants from plasma of 19 non-transmitting mothers from the U.S. Women Infant Transmission Study (WITS), enrolled in the pre-ART era. Maternal HIV Env variants from non-transmitting mothers had similar sensitivity to autologous plasma as observed for non-transmitting variants from transmitting mothers. In contrast, infant variants were on average 30% less sensitive to paired plasma neutralization compared to non-transmitted maternal variants from both transmitting and non-transmitting mothers (p=0.015). Importantly, a signature sequence analysis revealed that motifs enriched in env sequences from transmitting mothers were associated with broadly neutralizing antibody (bnAb) resistance. Altogether, our findings suggest that circulating maternal virus resistance to bnAb-mediated neutralization, but not autologous plasma neutralization, near the time of delivery, predicts increased MTCT risk. These results caution that enhancement of maternal plasma neutralization through passive or active vaccination during pregnancy could drive the evolution of variants fit for vertical transmission.

scholarly journals The US CDC RT-PCR probes for the Wuhan 2019-nCoV are non-specific for SARS - there is a better non-specific 500bp option (21852-22427) within the spike-protein

2020 ◽  
Author(s):  
Sandeep Chakraborty
Keyword(s):  
Virulent Strain ◽  
Spike Protein ◽  
World Health ◽  
Genomic Fragment ◽  
Rt Pcr ◽  
Inconclusive Result ◽  
The Us ◽  
The World ◽  
Significant Homology ◽  
Health Organization

The World Health Organization has declared the Wuhan coronavirus [1–3] outbreak a public health emer- gency on 30th Jan, 2020. An accurate detection of the Wuhan virus is imperative to avoid false positives, since 2019-nCoV [2,3] shares significant homology [4] with other species.On the 24th of Jan, the CDC has published a list of 3 probes (Fig 1) for detecting the 2019-nCoV. Detection of all three probes would give a positive result, while detection of one or two gives an ’inconclusive result’ (and obviously negative when none are found).All 3 probes will have significant homology in other strains (Table 1 and Fig 2 ) - specifically SARS (Severe Acute Respiratory Syndrome). A much more specific option is to look within a 500bp genomic fragment in the N-terminal of the spike protein (Accid:NC 045512.2 [2],21852-22427, SI.cdc:nCoVFULLSLICE.fa), which seems to the most perturbed in this virulent strain [5].It is also important to have a common repository for all countries to be following a similar protocol. Many papers do no provide what PCR was used to detect coronaviruses [6].

scholarly journals Fully Human Antibody Immunoglobulin from Transchromosomic Bovines is Potent Against SARS-CoV-2 Variant Pseudoviruses

2021 ◽  
Author(s):  
Thomas Luke ◽  
Hua Wu ◽  
Kristi A Egland ◽  
Eddie J Sullivan ◽  
Christoph L Bausch
Keyword(s):  
293T Cell ◽  
Spike Protein ◽  
World Health ◽  
Human Antibody ◽  
Phase 2 ◽  
Angiotensin Converting Enzyme 2 ◽  
The World ◽  
Health Organization ◽  
Transmembrane Serine Protease ◽  
Multiple Variants

SAB-185 is a fully human polyclonal anti-SARS-CoV-2 immunoglobulin produced from the plasma of transchromosomic bovines that are hyperimmunized with recombinant SARS-CoV-2 Wuhan-Hu-1 Spike protein. SAB-185 is being evaluated for efficacy in an adaptive phase 2/3 clinical trial. The World Health Organization (WHO) has identified multiple Variants-of-Concern and Variants-of-Interest (VOC/VOI) that have mutations in their Spike protein that appear to increase transmissibility and/or reduce the effectiveness of therapeutics and vaccines, among other parameters of concern. SAB-185 was evaluated using a lentiviral-based pseudovirus assay performed in a BSL2 environment that incorporates a stable 293T cell line expressing human angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). The results indicate that SAB-185 retained neutralization potency against multiple SARS-CoV-2 pseudovirus variants, including the Delta, Kappa and Lambda variants, that are supplanting other VOC/VOI in many countries and regions around the world.

Sign in / Sign up

Export Citation Format

Share Document