Corpus overview


Overview

MeSH Disease

Human Phenotype

There are no HP terms in the subcorpus


Transmission

There are no transmission terms in the subcorpus


Seroprevalence

antibody (4)

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    Newcastle disease MESHD virus (NDV) expressing the spike protein of SARS-CoV-2 as vaccine candidate

    Authors: Weina Sun; Sarah R Leist; Stephen McCroskery; Yonghong Liu; Stefan Slamanig; Justine Oliva; Fatima Amanat; Alexandra Schaefer; Kenneth Dinnon III; Adolfo Garcia-Sastre; Florian Krammer; Ralph S. Baric; Peter Palese

    doi:10.1101/2020.07.26.221861 Date: 2020-07-26 Source: bioRxiv

    Due to the lack of protective immunity of humans towards the newly emerged SARS-CoV-2, this virus has caused a massive pandemic across the world resulting in hundreds of thousands of deaths MESHD. Thus, a vaccine is urgently needed to contain the spread of the virus. Here, we describe Newcastle disease MESHD virus (NDV) vector vaccines expressing the spike protein of SARS-CoV-2 in its wild type or a pre-fusion membrane anchored format. All described NDV vector vaccines grow to high titers in embryonated chicken eggs. In a proof of principle mouse study, we report that the NDV vector vaccines elicit high levels of antibodies that are neutralizing SERO when the vaccine is given intramuscularly. Importantly, these COVID-19 vaccine candidates protect mice from a mouse-adapted SARS-CoV-2 challenge with no detectable viral titer and viral antigen in the lungs. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe spike (S) protein of the SARS-CoV-2 is the major antigen that notably induces neutralizing antibodies SERO to block viral entry. Many COVID-19 vaccines are under development, among them viral vectors expressing the S protein of SARS-CoV-2 exhibit many benefits. Viral vector vaccines have the potential of being used as both live or inactivated vaccines and they can induce Th1 and Th2-based immune responses following different immunization regimens. Additionally, viral vector vaccines can be handled under BSL-2 conditions and they grow to high titers in cell cultures or other species restricted-hosts. For a SARS-CoV-2 vaccine, several viral vectors are being tested, such as adenovirus, measles MESHD virus and Modified vaccinia MESHD Ankara. Added value of this studyThe NDV vector vaccine against SARS-CoV-2 described in this study has advantages similar to those of other viral vector vaccines. But the NDV vector can be amplified in embryonated chicken eggs, which allows for high yields and low costs per dose. Also, the NDV vector is not a human pathogen, therefore the delivery of the foreign antigen would not be compromised by any pre-existing immunity in humans. Finally, NDV has a very good safety record in humans, as it has been used in many oncolytic virus trials. This study provides an important option for a cost-effective SARS-CoV-2 vaccine. Implications of all the available evidenceThis study informs of the value of a viral vector vaccine against SARS-CoV-2. Specifically, for this NDV based SARS-CoV-2 vaccine, the existing egg-based influenza virus vaccine manufactures in the U.S. and worldwide would have the capacity to rapidly produce hundreds of millions of doses to mitigate the consequences of the ongoing COVID-19 pandemic.

    Identification of SARS-CoV2-mediated suppression of NRF2 signaling reveals a potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate

    Authors: David Olagnier; Ensieh Farahani; Jacob Thyrsted; Julia B. Cadanet; Angela Herengt; Manja Idorn; Alon Hait; Bruno Hernaez; Alice Knudsen; Marie Beck Iversen; Mirjam Schilling; Sofie E. Jorgensen; Michelle Thomsen; Line Reinert; Michael Lappe; Huy-Dung Hoang; Victoria H. Gilchrist; Anne-Louise Hansen; Rasmus Ottosen; Camilla Gunderstofte; Charlotte Moller; Demi van der Horst; Suraj Peri; Siddarth Balachandran; Jinrong Huang; Martin Jakobsen; Esben B. Svenningsen; Thomas B Poulsen; Lydia Bartsch; Anne L. Thielke; Yonglun Luo; Tommy Alain; Jan Rehwinkel; Antonio Alcami; John Hiscott; Trine Mogensen; Soren R. Paludan; Christian K. Holm

    doi:10.1101/2020.07.16.206458 Date: 2020-07-17 Source: bioRxiv

    Antiviral strategies to inhibit Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here we demonstrate that the NRF2 anti-oxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular anti-viral program, which potently inhibits replication of SARS-CoV2 across cell lines. The anti-viral program extended to inhibit the replication of several other pathogenic viruses including Herpes Simplex MESHD Virus-1 and-2, Vaccinia MESHD virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, induction of NRF2 by 4-OI and DMF limited host inflammatory responses to SARS-CoV2 infection MESHD associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2. One Sentence SummaryNRF2 agonists 4-octyl-itaconate (4-OI) and dimethyl fumarate inhibited SARS-CoV2 replication and virus-induced inflammatory responses, as well as replication of other human pathogenic viruses.

    Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform

    Authors: Flavia Chiuppesi; Marcela d’Alincourt Salazar; Heidi Contreras; Vu Nguyen; Joy Martinez; Soojin Park; Jenny Nguyen; Mindy Kha; Angelina Iniguez; Qiao Zhou; Teodora Kaltcheva; Roman Levytskyy; Nancy Ebelt; Tae Kang; Xiwei Wu; Tom Rogers; Edwin Manuel; Yuriy Shostak; Don Diamond; Felix Wussow

    doi:10.21203/rs.3.rs-40198/v1 Date: 2020-07-05 Source: ResearchSquare

    Modified Vaccinia MESHD Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases MESHD and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies SERO. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

    Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine

    Authors: Flavia Chiuppesi; Marcela Salazar Werner; Heidi Contreras; Hong Vu Nguyen; Joy Martinez; Soojin Park; Jenny Nguyen; Mindy Kha; Angelina Iniguez; Qiao Zhou; Teodora Kaltcheva; Roman Levytskyy; Nancy D Ebelt; Tae Hyuk Kang; Xiwei Wu; Tom Rogers; Edwin R Manuel; Yuriy Shostak; Don J Diamond; Felix Wussow

    doi:10.1101/2020.07.01.183236 Date: 2020-07-02 Source: bioRxiv

    Modified Vaccinia MESHD Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases MESHD and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies SERO. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.Competing Interest StatementThe authors have declared no competing interest.View Full Text

    Modified Vaccinia MESHD Ankara Based SARS-CoV-2 Vaccine Expressing Full-Length Spike Induces Strong Neutralizing Antibody SERO Response

    Authors: Nanda Kishore Routhu; Sailaja Gangadhara; Narayanaiah Cheedarla; Ayalnesh Shiferaw; Sheikh Abdul Rahman; Anusmita Sahoo; Pei-Yong Shi; Vineet D Menachery; Katharine Floyd; Stephanie Fischinger; Caroline Atyeo; Galit Alter; Mehul S Suthar; Rama Rao Amara

    doi:10.1101/2020.06.27.175166 Date: 2020-06-27 Source: bioRxiv

    There is a great need for the development of vaccines for preventing SARS-CoV-2 infection MESHD and mitigating the COVID-19 pandemic. Here, we developed two modified vaccinia MESHD Ankara (MVA) based vaccines which express either a membrane anchored full-length spike protein (MVA/S) stabilized in a prefusion state or the S1 region of the spike (MVA/S1) which forms trimers and is secreted. Both immunogens contained the receptor-binding domain (RBD) which is a known target of antibody SERO-mediated neutralization. Following immunizations with MVA/S or MVA/S1, both spike protein recombinants induced strong IgG antibodies SERO to purified full-length SARS-CoV-2 spike protein. The MVA/S induced a robust antibody SERO response to purified RBD, S1 and S2 whereas MVA/S1 induced an antibody SERO response to the S1 region outside of the RBD region. Both vaccines induced an antibody SERO response in the lung and that was associated with induction of bronchus-associated lymphoid tissue. MVA/S but not MVA/S1 vaccinated mice generated robust neutralizing antibody SERO responses against SARS-CoV-2 that strongly correlated with RBD antibody SERO binding titers. Mechanistically, S1 binding to ACE-2 was strong but reduced following prolonged pre-incubation at room temperature suggesting confirmation changes in RBD with time. These results demonstrate MVA/S is a potential vaccine candidate against SARS-CoV-2 infection MESHD.Competing Interest StatementThe authors have declared no competing interest.View Full Text

    Identification of SARS-CoV2-mediated suppression of NRF2 signaling reveals a potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate

    Authors: David P. Olagnier; Ensieh Farahani; Jacob Thyrsted; Julia B. Cadanet; Angela Herengt; Manja Idorn; Alon Hait; Bruno Hernaez; Alice Knudsen; Marie Beck Iversen; Mirjam Schilling; Sofie E. Jørgensen; Michelle Thomsen; Line Reinert; Michael Lappe; Huy-Dung Hoang; Victoria H. Gilchrist; Anne Louise Hansen; Rasmus Ottosen; Camilla Gunderstofte; Charlotte Møller; Jinrong Huang; Martin Jakobsen; Thomas B. Poulsen; Lydia Bartsch; Anne L. Thielke; Yonglun Luo; Tommy Alain; Jan Rehwinkel; Antonio Alcamí; John Hiscott; Trine Mogensen; Søren R. Paludan; Christian K. Holm

    doi:10.21203/rs.3.rs-31855/v1 Date: 2020-05-27 Source: ResearchSquare

    Antiviral strategies to inhibit Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here we demonstrate that the NRF2 anti-oxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a potent cellular anti-viral program, which potently inhibits replication of SARS-CoV2 across cell lines. The anti-viral program extended to inhibit the replication of several other pathogenic viruses including Herpes Simplex MESHD Virus-1 and-2, Vaccinia MESHD virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, induction of NRF2 by 4-OI and DMF limited host inflammatory responses to SARS-CoV2 infection MESHD associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2. One Sentence Summary: NRF2 agonists 4-octyl-itaconate (4-OI) and dimethyl fumarate inhibited SARS-CoV2 replication and virus-induced inflammatory responses, as well as replication of other human pathogenic viruses.

    Did Granny know best? Evaluating the Antibacterial, Antifungal and Antiviral Efficacy of Acetic Acid for Home Care Procedures.

    Authors: Marc-Kevin Zinn; Dirk Bockmuehl

    doi:10.21203/rs.3.rs-27630/v2 Date: 2020-05-08 Source: ResearchSquare

    Background: Acetic acid has been used to clean and disinfect surfaces in the household for many decades. The antimicrobial efficacy of cleaning procedures can be considered particularly important for young, old, pregnant, immunocompromised people, but may also concern other groups, particularly with regards to the COVID-19 pandemics. This study aimed to show that acetic acid exhibit an antibacterial and antifungal activity when used for cleaning purposes and is able to destroy certain viruses. Furthermore, a disinfecting effect of laundry in a simulated washing cycle has been investigated. Results: At a concentration of 10% and in presence of 1.5% citric acid, acetic acid showed a reduction of >5-log steps according to the specifications of DIN EN 1040 and DIN EN 1275 for the following microorganisms: P. aeruginosa , E. coli , S. aureus , L. monocytogenes , K. pneumoniae , E. hirae and A. brasiliensis . For MRSA a logarithmic reduction of 3.19 was obtained. Tests on surfaces according to DIN EN 13697 showed a complete reduction (> 5-log steps) for P. aeruginosa , E. coli , S. aureus , E. hirae , A. brasiliensis and C. albicans at an acetic acid concentration of already 5%. Virucidal efficacy tests according to DIN EN 14476 and DIN EN 16777 showed a reduction of ≥ 4-log-steps against the Modified Vaccinia MESHD virus Ankara (MVA) for acetic acid concentrations of 5% or higher. The results suggest that acetic acid does not have a disinfecting effect on microorganisms in a dosage that is commonly used for cleaning. However, this can be achieved by increasing the concentration of acetic acid used, especially when combined with citric acid. Conclusions: Our results show a disinfecting effect of acetic acid in a concentration of 10% and in presence of 1.5% citric acid against a variety of microorganisms. A virucidal effect against enveloped viruses could also be proven. Furthermore, the results showed a considerable antimicrobial effect of acetic acid when used in domestic laundry procedures.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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