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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (5)

ProteinS (5)

ProteinE (1)

ComplexRdRp (1)

ORF1 (1)


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    Complete Protection of Nasal and Lung Airways Against SARS-CoV-2 Challenge by Antibody Plus Th1 HGNC Dominant N- and S-Specific T-Cell Responses to Subcutaneous Prime and Thermally-Stable Oral Boost Bivalent hAd5 Vaccination in an NHP Study

    Authors: Elizabeth Gabitzsch; Jeffrey T Safrit; Mohit Verma; Adrian Rice; Peter Sieling; Lise Zakin; Annie Shin; Brett Morimoto; Helty Adisetiyo; Raymond Wong; Ashish Bezawada; Kyle Dinkins; Joseph Balint; Victor Peykov; Hermes Garban; Philip Liu; Andrew Bacon; Jeff Drew; Patricia Spilman; Lennie Sender; Shahrooz Rabizadeh; Kayvan Niazi; Patrick Soon-Shiong

    doi:10.1101/2020.12.08.416297 Date: 2020-12-09 Source: bioRxiv

    BackgroundTo address the dire need for a safe and effective vaccine to protect individuals from and reduce transmission of SARS-CoV-2, we developed a COVID-19 MESHD vaccine that elicits not only robust humoral responses but also activates T cells. Our bivalent vaccine expresses both an optimized viral spike (S) protein PROTEIN S) protein HGNC (S-Fusion) and the viral nucleocapsid (N) protein PROTEIN with an Enhanced T-cell Stimulation Domain (N-ETSD) that directs N to the endo/lysosomal subcellular compartment to enhance MHC class II responses. The vaccine antigens are delivered by the second-generation adenovirus serotype 5 [E1-, E2b-, E3-] platform (hAd5) that has been safely administered and found to be effective in generating tumor MESHD-specific T cells even in the presence of pre-existing adenovirus immunity. Here, we report our findings on the safety and efficacy of our hAd5 S-Fusion + N-ETSD subcutaneous (SC) prime and thermally-stable oral boost vaccine in generating SARS-CoV-2-neutralizing antibodies, eliciting N- and S-specific T-cell responses, and providing complete protection with the clearing of virus after challenge in Non-Human Primates (NHP). A key objective of the study was to explore the efficacy of a novel thermally-stable oral hAd5 S-Fusion + N-ETSD to serve as a booster dose following an SC prime. MethodsGroup 1 NHP received the hAd5 S-Fusion + N-ETSD vaccine on Days 0 and 14 by SC injection (1011 VP), and on Day 28 by a single oral boost (1010 VP); Group 2 received vaccination on the same schedule, but with an SC prime and two oral boosts. Group 3 placebo NHP were dosed with vehicle-only SC-oral-oral. Blood for the isolation of sera and PBMCs was collected throughout the study. ELISA was used for determination of anti-S IgG levels, cPass for presence of neutralizing antibodies, and ELISpot for interferon-{gamma HGNC}( IFN-{gamma}) HGNC and interleukin-4 HGNC ( IL-4 HGNC) secretion by T cells. On Study Day 56, all NHP were challenged with intratracheal/intranasal 1 x 106 TCID50/mL SARS-CoV-2. Bronchoalveolar lavage (BAL) samples were collected on Day 42 pre-challenge and at several time points post-challenge; nasal swabs were collected daily post-challenge. NHP were euthanized on Study Day 70 and tissue collected for histopathological analyses. Viral load and active viral replication were determined in BAL and nasal swab specimens by RT qPCR of genomic and subgenomic RNA, respectively. Safety was determined by cage-side observations such as weight as well as hematology and clinical chemistry analyses of blood. ResultsThe hAd5 S-Fusion + N-ETSD vaccine, both SC and oral, elicited no apparent toxicity MESHD seen in clinical chemistry, hematology, or cage-side observations. Neutralizing antibodies were induced in 9 of 10 vaccinated NHP and anti-S IgG positive titers in 10 out of 10. Th1 HGNC dominant T-cell responses were elicited by both S and N antigens, with responses being greater for N. Viral replication was inhibited from Day 1 post-SARS-CoV-2 challenge with complete protection in all (10/10) primates within 7 days of challenge from both nasal passages and lung. Replicating SARS-CoV-2 dropped immediately and was undetectable as soon 3 days post-challenge. There was a rapid decline in lymphocytes from the periphery on Day 1 post-challenge and a rebound within 3 days following challenge that was significantly higher by Day 14 post-challenge in Group 1 as compared to Group 3 placebo NHP. ConclusionsIn the rhesus macaque NHP model, the bivalent hAd5 S-Fusion + N-ETSD subcutaneous and oral vaccine provided complete protection of nasal passages and lung against SARS-CoV-2 challenge by eliciting neutralizing antibodies plus Th1 HGNC dominant N- and S-specific T-cell responses. Inhibition of viral replication within the first 24 hours post-challenge, in vaccinated NHP compared to placebo NHP, suggests the presence of SARS-CoV-2-specific cytotoxic T cells that rapidly cleared infected cells. The rapidity of clearance implies that shedding of live viruses may be attenuated as a result of vaccination and thus the vaccine has the potential to prevent transmission of virus by infected individuals. Clinical trials of hAd5 S-Fusion + N-ETSD are ongoing. The hAd5 S-Fusion + N-ETSD subcutaneous prime/boost vaccine has completed Phase 1 clinical trials and Phase 2/3 trials are actively recruiting. The thermally-stable oral vaccine will enter Phase 1 trials as a prime and boost, as well as explored to provide a boost to subcutaneous vaccination.

    Long-Term Persistence of Spike Antibody and Predictive Modeling of Antibody Dynamics Following Infection with SARS-CoV-2

    Authors: Louis Grandjean; Anja Saso; Arturo Torres Ortiz; Tanya Lam; James Hatcher; Rosie Thistlethwaite; Mark Harris; Timothy Best; Marina Johnson; Helen Wagstaffe; Elizabeth Ralph; Annabelle Mai; Caroline Colijn; Judith Breuer; Matthew Buckland; Kimberly Gilmour; David Goldblatt; - The Co-Stars Study Team

    doi:10.1101/2020.11.20.20235697 Date: 2020-11-23 Source: medRxiv

    Background: Antibodies to Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2) have been shown to neutralize the virus in-vitro. Similarly, animal challenge models suggest that neutralizing antibodies isolated from SARS-CoV-2 infected MESHD individuals prevent against disease upon re-exposure to the virus. Understanding the nature and duration of the antibody response following SARS-CoV-2 infection MESHD is therefore critically important. Methods: Between April and October 2020 we undertook a prospective cohort study of 3555 healthcare workers in order to elucidate the duration and dynamics of antibody responses following infection with SARS-CoV-2. After a formal performance evaluation against 169 PCR confirmed cases and negative controls, the Meso-Scale Discovery assay was used to quantify in parallel, antibody titers to the SARS-CoV-2 nucleoprotein (N PROTEIN), spike (S) protein PROTEIN and the receptor-binding-domain (RBD) of the S-protein HGNC S-protein PROTEIN. All seropositive participants were followed up monthly for a maximum of 7 months; those participants that were symptomatic, with known dates of symptom-onset, seropositive by the MSD assay and who provided 2 or more monthly samples were included in the analysis. Survival analysis was used to determine the proportion of sero-reversion (switching from positive to negative) from the raw data. In order to predict long-term antibody dynamics, two hierarchical longitudinal Gamma models were implemented to provide predictions for the lower bound (continuous antibody decay to zero, 'Gamma-decay') and upper bound (decay-to-plateau due to long lived plasma cells, 'Gamma-plateau') long-term antibody titers. Results: A total of 1163 samples were provided from 349 of 3555 recruited participants who were symptomatic, seropositive by the MSD assay, and were followed up with 2 or more monthly samples. At 200 days post symptom onset, 99% of participants had detectable S-antibody whereas only 75% of participants had detectable N-antibody. Even under our most pessimistic assumption of persistent negative exponential decay, the S-antibody was predicted to remain detectable in 95% of participants until 465 days [95% CI 370-575] after symptom onset. Under the Gamma-plateau model, the entire posterior distribution of S-antibody titers at plateau remained above the threshold for detection indefinitely. Surrogate neutralization assays demonstrated a strong positive correlation between antibody titers to the S-protein PROTEIN S-protein HGNC and blocking of the ACE-2 HGNC receptor in-vitro [R2=0.72, p<0.001]. By contrast, the N-antibody waned rapidly with a half-life of 60 days [95% CI 52-68]. Discussion: This study has demonstrated persistence of the spike antibody in 99% of participants at 200 days following SARS-CoV-2 symptoms MESHD and rapid decay of the nucleoprotein PROTEIN antibody. Diagnostic tests or studies that rely on the N-antibody as a measure of seroprevalence must be interpreted with caution. Our lowest bound prediction for duration of the spike antibody was 465 days and our upper bound predicted spike antibody to remain indefinitely in line with the long-term seropositivity reported for SARS-CoV infection MESHD. The long-term persistence of the S-antibody, together with the strong positive correlation between the S-antibody and viral surrogate neutralization in-vitro, has important implications for the duration of functional immunity following SARS-CoV-2 infection MESHD.

    Temporal patterns in the evolutionary genetic distance of SARS-CoV-2 during the COVID-19 MESHD COVID-19 MESHD pandemic

    Authors: Jingzhi Lou; Shi Zhao; Lirong Cao; Zigui Chen; Renee WY Chan; Marc KC Chong; Benny CY Zee; Paul KS Chan; Maggie H Wang; Marian J Killip; Patricia A Cane; Christine B Bruce; Allen D.G Roberts; Guanghui Tian; Haji A. Aisa; Tianwen Hu; Daibao Wei; Yi Jiang; Gengfu Xiao; Hualiang Jiang; Leike Zhang; Xuekui Yu; Jingshan Shen; Shuyang Zhang; H. Eric Xu

    doi:10.1101/2020.11.01.363739 Date: 2020-11-02 Source: bioRxiv

    Background: During the pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD), the genetic mutations occurred in severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) cumulatively or sporadically. In this study, we employed a computational approach to identify and trace the emerging patterns of the SARS-CoV-2 mutations, and quantify accumulative genetic distance across different periods and proteins. Methods: Full-length human SARS-CoV-2 strains in United Kingdom were collected. We investigated the temporal variation in the evolutionary genetic distance defined by the Hamming distance since the start of COVID-19 pandemic MESHD. Findings: Our results showed that the SARS-CoV-2 was in the process of continuous evolution, mainly involved in spike protein (S PROTEIN S protein HGNC), the RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN) region of open reading frame 1 PROTEIN ( ORF1 PROTEIN) and nucleocapsid protein (N PROTEIN protein). By contrast, mutations in other proteins were sporadic and genetic distance to the initial sequenced strain did not show an increasing trend.

    Humoral Response Dynamics Following Infection with SARS-CoV-2

    Authors: Louis Grandjean; Anja Saso; Arturo Ortiz; Tanya Lam; James Hatcher; Rosie Thistlethwaite; Mark Harris; Timothy Best; Marina Johnson; Helen Wagstaffe; Elizabeth Ralph; Annabelle Mai; Caroline Colijn; Judith Breuer; Matthew Buckland; Kimberly Gilmour; David Goldblatt; - The Co-Stars Study Team

    doi:10.1101/2020.07.16.20155663 Date: 2020-07-21 Source: medRxiv

    Introduction: Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2) specific antibodies have been shown to neutralize the virus in-vitro. Understanding antibody dynamics following SARS-CoV-2 infection MESHD is therefore crucial. Sensitive measurement of SARS-CoV-2 antibodies is also vital for large seroprevalence surveys which inform government policies and public health interventions. However, rapidly waning antibodies following SARS-CoV-2 infection MESHD could jeopardize the sensitivity of serological testing on which these surveys depend. Methods: This prospective cohort study of SARS-CoV-2 humoral dynamics in a central London hospital analyzed 137 serial samples collected from 67 participants seropositive to SARS-CoV-2 by the Meso-Scale Discovery assay. Antibody titers were quantified to the SARS-CoV-2 nucleoprotein (N PROTEIN), spike (S-)protein PROTEIN S-)protein HGNC and the receptor-binding-domain (RBD) of the S-protein HGNC S-protein PROTEIN. Titers were log-transformed and a multivariate log-linear model with time-since-infection and clinical variables was fitted by Bayesian methods. Results: The mean estimated half-life of the N-antibody was 52 days (95% CI 42-65). The S- and RBD-antibody had significantly longer mean half-lives of 81 days (95% CI 61-111) and 83 days (95% CI 55-137) respectively. An ACE-2-receptor competition assay demonstrated significant correlation between the S and RBD-antibody titers and ACE2-receptor blocking in-vitro. The time-to-a-negative N-antibody test for 50% of the seropositive population was predicted to be 195 days (95% CI 163-236). Discussion: After SARS-CoV-2 infection MESHD, the predicted half-life of N-antibody was 52 days with 50% of seropositive participants becoming seronegative to this antibody at 195 days. Widely used serological tests that depend on the N-antibody will therefore significantly underestimate the prevalence of infection following the majority of infections.

    Scope of Natural Plant Extract to Deactivate COVID-19 MESHD

    Authors: Md Abdus Shahid; Mohammad Asaduzzaman Chowdhury; Mohammod Abul Kashem

    doi:10.21203/rs.3.rs-19240/v1 Date: 2020-03-24 Source: ResearchSquare

    The outbreak of coronavirus disease 2019 MESHD ( COVID-19 MESHD) has emerged as a severe threat for public health and economy throughout the world. The structure of corona virus is composed of RNA based proteins that contains amino (-NH2) and carboxyl (-COOH) groups.  It includes nucleocapsid protein (N PROTEIN- protein), spike PROTEIN protein (S PROTEIN S-protein HGNC protein), envelope PROTEIN and hemagglutinin-esterase dimer (HE). These proteins affect adversely on human gastrointestinal system, heart, kidney, liver, and central nervous system leading to several organ damages. This investigation reveals that the extracted components of natural plants, especially hydroxyl (-OH) groups react chemically to deactivate the active components of the virus by esterification   process. As a case study, using one of the natural resources, as for example, licorice (Glycyrrhiza glabra) which has the components of glycyrrhizin, glycyrrhetic acid, liquiritin and isoliquiritin that can be used to neutralize the activeness of COVID-19 MESHD and it can be used as an antiviral drug. The extracted licorice is further processed with PVA solution to form antiviral nano-membrane for potential application as wound dressing materials, musk, gloves and against skin infection MESHD by electrospinning.  The morphology of the membrane is characterized using scanning electron microscope (SEM). The research suggests that the other plants having deactivate components against virus can be applicable to resolve the human health crisis of the globe. 

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MeSH Disease
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SARS-CoV-2 Proteins


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