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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332623

ABSTRACT

Recombination is a crucial process in the evolution of many organisms. Although the evolutionary reasons behind its occurrence in RNA viruses are debated, this phenomenon has been associated with major epidemiological events such as virus host range expansion, antigenic shift or variation in virulence 1,2, and this process occurs frequently in positive strand RNA viruses such as coronaviruses. The SARS-CoV-2 pandemic has been associated with the repeated emergence of variants of concern presenting increased transmissibility, severity or immune escape 3. The recent extensive circulation of Delta worldwide and its subsequent replacement by viruses of the Omicron lineage 4 (BA.1 then BA.2), have created conditions for genetic exchanges between viruses with both genetic diversity and phenotypic specificities 5-7. Here we report the identification and in vitro and in vivo characterization of a Delta-Omicron recombinant in Europe. This recombinant exhibits immune escape properties similar to Omicron, while its behavior in mice expressing the human ACE2 receptor is more similar to Delta. This recombinant provides a unique and natural opportunity to better understand the genotype to phenotype links in SARS-CoV-2.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330759

ABSTRACT

Two years into the COVID-19 pandemic there is still a need for vaccines to effectively control the spread of novel SARS-CoV-2 variants and associated cases of severe disease. Here we report a messenger RNA vaccine directly encoding for a nanoparticle displaying 60 receptor binding domains (RBDs) of SARS-CoV-2 that acts as a highly effective antigen. A construct encoding the RBD of the delta variant elicits robust neutralizing antibody response with neutralizing titers an order of magnitude above currently approved mRNA vaccines. The construct also provides protective immunity against the delta variant in a widely used transgenic mouse model. We ultimately find that the proposed mRNA RBD nanoparticle-based vaccine provides a flexible platform for rapid development and will likely be of great value in combatting current and future SARS-CoV-2 variants of concern.

3.
Nat Commun ; 12(1): 6277, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1493102

ABSTRACT

Several COVID-19 vaccines have now been deployed to tackle the SARS-CoV-2 pandemic, most of them based on messenger RNA or adenovirus vectors.The duration of protection afforded by these vaccines is unknown, as well as their capacity to protect from emerging new variants. To provide sufficient coverage for the world population, additional strategies need to be tested. The live pediatric measles vaccine (MV) is an attractive approach, given its extensive safety and efficacy history, along with its established large-scale manufacturing capacity. We develop an MV-based SARS-CoV-2 vaccine expressing the prefusion-stabilized, membrane-anchored full-length S antigen, which proves to be efficient at eliciting strong Th1-dominant T-cell responses and high neutralizing antibody titers. In both mouse and golden Syrian hamster models, these responses protect the animals from intranasal infectious challenge. Additionally, the elicited antibodies efficiently neutralize in vitro the three currently circulating variants of SARS-CoV-2.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Genetic Vectors , Immunity , Adenoviridae , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Cricetinae , Cytokines , Female , Immunization , Immunization, Secondary , Male , Measles Vaccine/immunology , Mesocricetus , Mice , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
4.
J Biol Chem ; 298(1): 101290, 2022 01.
Article in English | MEDLINE | ID: covidwho-1472024

ABSTRACT

The current COVID-19 pandemic illustrates the importance of obtaining reliable methods for the rapid detection of SARS-CoV-2. A highly specific and sensitive diagnostic test able to differentiate the SARS-CoV-2 virus from common human coronaviruses is therefore needed. Coronavirus nucleoprotein (N) localizes to the cytoplasm and the nucleolus and is required for viral RNA synthesis. N is the most abundant coronavirus protein, so it is of utmost importance to develop specific antibodies for its detection. In this study, we developed a sandwich immunoassay to recognize the SARS-CoV-2 N protein. We immunized one alpaca with recombinant SARS-CoV-2 N and constructed a large single variable domain on heavy chain (VHH) antibody library. After phage display selection, seven VHHs recognizing the full N protein were identified by ELISA. These VHHs did not recognize the nucleoproteins of the four common human coronaviruses. Hydrogen Deuterium eXchange-Mass Spectrometry (HDX-MS) analysis also showed that these VHHs mainly targeted conformational epitopes in either the C-terminal or the N-terminal domains. All VHHs were able to recognize SARS-CoV-2 in infected cells or on infected hamster tissues. Moreover, the VHHs could detect the SARS variants B.1.17/alpha, B.1.351/beta, and P1/gamma. We propose that this sandwich immunoassay could be applied to specifically detect the SARS-CoV-2 N in human nasal swabs.


Subject(s)
Enzyme-Linked Immunosorbent Assay/methods , Nucleocapsid Proteins/analysis , SARS-CoV-2/immunology , Single-Domain Antibodies/immunology , Animals , Cricetinae , Electrophoresis, Polyacrylamide Gel , Humans , Limit of Detection , Nucleocapsid Proteins/immunology
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