scholarly journals COVID 19 breakthrough infection risk: a simple physical model describing the dependence on antibody concentration

2021 ◽  
Author(s):  
David E Williams
Keyword(s):  
Vaccine Efficacy ◽  
Infection Risk ◽  
Antibody Concentration ◽  
Receptor Binding Domain ◽  
Breakthrough Infection ◽  
Virus Surface ◽  
Domain Antibody ◽  
Simple Physical Model ◽  
Rational Explanation ◽  
Spike Proteins

Abstract The empirically-observed dependence on blood IgG anti-receptor binding domain antibody concentration of SARS-CoV-2 vaccine efficacy against infection has a rational explanation in the statistics of binding of antibody to spike proteins on the virus surface: namely that the probability of protection is the probability of antibody binding to more than a critical number of the spike proteins protruding from the virus. The model is consistent with the observed antibody concentrations required to induce immunity and with the observed dependence of vaccine efficacy on antibody concentration and thus is a useful tool in the development of models to relate, for an individual person, risk of breakthrough infection given measured antibody concentration

scholarly journals COVID 19 breakthrough infection risk: a simple physical model describing the dependence on antibody concentration

2021 ◽  
Author(s):  
David Williams
Keyword(s):  
Vaccine Efficacy ◽  
Infection Risk ◽  
Antibody Concentration ◽  
Receptor Binding Domain ◽  
Breakthrough Infection ◽  
Virus Surface ◽  
Domain Antibody ◽  
Simple Physical Model ◽  
Rational Explanation ◽  
Spike Proteins

Abstract The empirically-observed dependence on blood IgG anti-receptor binding domain antibody concentration of SARS-CoV-2 vaccine efficacy against infection has a rational explanation in the statistics of binding of antibody to spike proteins on the virus surface: namely that the probability of protection is the probability of antibody binding to more than a critical number of the spike proteins protruding from the virus. The model is consistent with the observed antibody concentrations required to induce immunity and with the observed dependence of vaccine efficacy on antibody concentration and thus is a useful tool in the development of models to relate, for an individual person, risk of breakthrough infection given measured antibody concentration

scholarly journals COVID 19 breakthrough infection risk: a simple physical model describing the dependence on antibody concentration

2021 ◽  
Author(s):  
David Williams
Keyword(s):  
Physical Model ◽  
Vaccine Efficacy ◽  
Infection Risk ◽  
Antibody Concentration ◽  
Critical Number ◽  
Breakthrough Infection ◽  
Virus Surface ◽  
Simple Physical Model ◽  
Rational Explanation ◽  
Spike Proteins

The empirically-observed dependence of SARS-CoV-2 vaccine efficacy on antibody concentration has a rational explanation in the statistics of binding of antibody to spike proteins on the virus surface: namely that the probability of protection is the probability of antibody binding to more than a critical number of the spike proteins protruding from the virus. The model is consistent with the observed antibody concentrations required to induce immunity.

scholarly journals Correlation of the Commercial Anti-SARS-CoV-2 Receptor Binding Domain Antibody Test with the Chemiluminescent Reduction Neutralizing Test and Possible Detection of Antibodies to Emerging Variants

2021 ◽  
Author(s):  
Yoshitomo Morinaga ◽  
Hideki Tani ◽  
Yasushi Terasaki ◽  
Satoshi Nomura ◽  
Hitoshi Kawasuji ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Vaccine Efficacy ◽  
Clinical Laboratory ◽  
Test Validity ◽  
Antibody Test ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Domain Antibody

This study provides a diagnostic evidence of test validity, which can lead to vaccine efficacy and proof of recovery after COVID-19. It is not easy to know neutralization against SARS-CoV-2 in the clinical laboratory because of technical and biohazard issues.

Detection of SARS-CoV-2 Receptor-Binding Domain Antibody using a HiBiT-Based Bioreporter

10.3791/62488 ◽  
2021 ◽  
Author(s):  
Reza Rezaei ◽  
Abera Surendran ◽  
Ragunath Singaravelu ◽  
Taylor R. Jamieson ◽  
Parisa Taklifi ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Domain Antibody

scholarly journals Unraveling the stability landscape of mutations in the SARS-CoV-2 receptor-binding domain

2020 ◽  
Author(s):  
Mohamed Raef Smaoui ◽  
Hamdi Yahyaoui
Keyword(s):  
Receptor Binding ◽  
Single Point ◽  
Protein Structures ◽  
Point Mutations ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Point Mutant ◽  
The Stability ◽  
Spike Proteins

Abstract The interaction between the receptor-binding domain of the SARS-CoV-2 spike glycoprotein and the ACE2 enzyme is believed to be the entry point of the virus into various cells in the body, including the lungs, heart, liver, and kidneys. The current focus of several therapeutic design efforts explore attempts at affecting the binding interaction between the two proteins to limit the activity of the virus and disease progression. In this work, we analyze the stability of the spike protein under all possible single-point mutations in the receptor-binding domain and computationally explore mutations that can affect the binding with the ACE2 enzyme. We unravel the mutation landscape of the receptor region and assess the toxicity potential of single and multi-point mutations, generating insights for future vaccine efforts on potential mutations that might further stabilize the spike protein and increase its infectivity. We developed a tool, called SpikeMutator, to construct full atomic protein structures of the mutant spike proteins and shared a database of 3,800 single-point mutant structures. We analyzed the recent 65,000 reported spike sequences across the globe and observed the emergence of stable multi-point mutant structures. Using the landscape, we searched through 7.5 million possible 2-point mutation combinations and report that the (R355D K424E) mutation produces one of the strongest spike proteins that therapeutic efforts should investigate for the sake of developing an effective vaccine.

scholarly journals What Binds Cationic Photosensitizers Better: Brownian Dynamics Reveals Key Interaction Sites on Spike Proteins of SARS-CoV, MERS-CoV, and SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1615
Author(s):  
Vladimir Fedorov ◽  
Ekaterina Kholina ◽  
Sergei Khruschev ◽  
Ilya Kovalenko ◽  
Andrew Rubin ◽  
...  
Keyword(s):  
Binding Site ◽  
Brownian Dynamics ◽  
Zinc Phthalocyanine ◽  
Heptad Repeat ◽  
Receptor Binding Domain ◽  
Large Area ◽  
S Protein ◽  
Interaction Sites ◽  
S Proteins ◽  
Spike Proteins

We compared the electrostatic properties of the spike proteins (S-proteins) of three coronaviruses, SARS-CoV, MERS-CoV, and SARS-CoV-2, and their interactions with photosensitizers (PSs), octacationic octakis(cholinyl)zinc phthalocyanine (Zn-PcChol8+) and monocationic methylene blue (MB). We found a major common PS binding site at the connection of the S-protein stalk and head. The molecules of Zn-PcChol8+ and MB also form electrostatic encounter complexes with large area of negative electrostatic potential at the head of the S-protein of SARS-CoV-2, between fusion protein and heptad repeat 1 domain. The top of the SARS-CoV spike head demonstrates a notable area of electrostatic contacts with Zn-PcChol8+ and MB that corresponds to the N-terminal domain. The S-protein protomers of SARS-CoV-2 in “open” and “closed” conformations demonstrate different ability to attract PS molecules. In contrast with Zn-PcChol8+, MB possesses the ability to penetrate inside the pocket formed as a result of SARS-CoV-2 receptor binding domain transition into the “open” state. The existence of binding site for cationic PSs common to the S-proteins of SARS-CoV, SARS-CoV-2, and MERS-CoV creates prospects for the wide use of this type of PSs to combat the spread of coronaviruses.

scholarly journals Trimeric SARS-CoV-2 Spike Proteins Produced from CHO Cells in Bioreactors Are High-Quality Antigens

Processes ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 1539
Author(s):  
Paco Pino ◽  
Joeri Kint ◽  
Divor Kiseljak ◽  
Valentina Agnolon ◽  
Giampietro Corradin ◽  
...  
Keyword(s):  
Diagnostic Tests ◽  
Neutralizing Antibodies ◽  
Good Manufacturing Practice ◽  
Spike Protein ◽  
High Quality ◽  
Virus Surface ◽  
Corona Virus ◽  
Global Demand ◽  
Diagnostic Sensitivity And Specificity ◽  
Spike Proteins

The spike protein of the pandemic human corona virus is essential for its entry into human cells. In fact, most neutralizing antibodies against Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) are directed against the Virus-surface exposed spike protein, making it the antigen of choice for use in vaccines and diagnostic tests. In the current pandemic context, global demand for spike proteins has rapidly increased and could exceed hundreds of grams to kilograms annually. Coronavirus spikes are large heavily glycosylated homo-trimeric complexes, with inherent instability. The poor manufacturability now threatens the availability of these proteins for vaccines and diagnostic tests. Here, we outline scalable, Good Manufacturing Practice (GMP) compliant, and chemically defined processes for the production of two cell-secreted stabilized forms of the trimeric spike proteins (Wuhan and D614G variant). The processes are chemically defined and based on clonal suspension-CHO cell populations and on protein purification via a two-step scalable downstream process. The trimeric conformation was confirmed using electron microscopy and HPLC analysis. Binding to susceptible cells was shown using a virus-inhibition assay. The diagnostic sensitivity and specificity for detection of serum SARS-CoV-2-specific-immunoglobulin molecules was found to exceed that of spike fragments (Spike subunit-1, S1 and Receptor Binding Domain, RBD). The process described here will enable production of sufficient high-quality trimeric spike protein to meet the global demand for SARS-CoV-2 diagnostic tests and potentially vaccines.

scholarly journals RV144 Vaccine Imprinting Constrained HIV-1 Evolution Following Breakthrough Infection

2021 ◽  
Author(s):  
Eric Lewitus ◽  
Eric Sanders-Buell ◽  
Meera Bose ◽  
Anne Marie O’Sullivan ◽  
Kultida Poltavee ◽  
...  
Keyword(s):  
Placebo Group ◽  
Vaccine Efficacy ◽  
Vaccine Group ◽  
Efficacy Trial ◽  
Breakthrough Infection ◽  
Diversifying Selection ◽  
Hiv 1 ◽  
Rv144 Vaccine ◽  
Over Time ◽  
Roll Out

Abstract The scale of the HIV-1 epidemic underscores the need for a vaccine. The multitude of circulating HIV-1 strains together with HIV-1’s high evolvability hint that HIV-1 could adapt to a future vaccine. Here we wanted to investigate the effect of vaccination on the evolution of the virus post-breakthrough infection. We analyzed 2,635 HIV-1 env sequences sampled up to a year post-diagnosis from 110 vaccine and placebo participants who became infected in the RV144 vaccine efficacy trial. We showed that the Env signatures sites that were previously identified to distinguish vaccine and placebo participants were maintained over time. In addition, fewer sites were under diversifying selection in the vaccine group than in the placebo group. These results indicate that HIV-1 would possibly adapt to a vaccine upon its roll out.

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