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1.
Cell Rep ; 37(11): 110114, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1604785

ABSTRACT

Messenger RNA-based vaccines against COVID-19 induce a robust anti-SARS-CoV-2 antibody response with potent viral neutralization activity. Antibody effector functions are determined by their constant region subclasses and by their glycosylation patterns, but their role in vaccine efficacy is unclear. Moreover, whether vaccination induces antibodies similar to those in patients with COVID-19 remains unknown. We analyze BNT162b2 vaccine-induced IgG subclass distribution and Fc glycosylation patterns and their potential to drive effector function via Fcγ receptors and complement pathways. We identify unique and dynamic pro-inflammatory Fc compositions that are distinct from those in patients with COVID-19 and convalescents. Vaccine-induced anti-Spike IgG is characterized by distinct Fab- and Fc-mediated functions between different age groups and in comparison to antibodies generated during natural viral infection. These data highlight the heterogeneity of Fc responses to SARS-CoV-2 infection and vaccination and suggest that they support long-lasting protection differently.


Subject(s)
COVID-19/immunology , Glycosylation/drug effects , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Viral/immunology , COVID-19 Vaccines/metabolism , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Israel/epidemiology , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Vaccination/methods , Vaccines, Synthetic/immunology , Vaccines, Synthetic/metabolism , /metabolism
2.
Nature ; 589(7840): 125-130, 2021 01.
Article in English | MEDLINE | ID: covidwho-752477

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic1. To understand the pathogenicity and antigenic potential of SARS-CoV-2 and to develop therapeutic tools, it is essential to profile the full repertoire of its expressed proteins. The current map of SARS-CoV-2 coding capacity is based on computational predictions and relies on homology with other coronaviruses. As the protein complement varies among coronaviruses, especially in regard to the variety of accessory proteins, it is crucial to characterize the specific range of SARS-CoV-2 proteins in an unbiased and open-ended manner. Here, using a suite of ribosome-profiling techniques2-4, we present a high-resolution map of coding regions in the SARS-CoV-2 genome, which enables us to accurately quantify the expression of canonical viral open reading frames (ORFs) and to identify 23 unannotated viral ORFs. These ORFs include upstream ORFs that are likely to have a regulatory role, several in-frame internal ORFs within existing ORFs, resulting in N-terminally truncated products, as well as internal out-of-frame ORFs, which generate novel polypeptides. We further show that viral mRNAs are not translated more efficiently than host mRNAs; instead, virus translation dominates host translation because of the high levels of viral transcripts. Our work provides a resource that will form the basis of future functional studies.


Subject(s)
Gene Expression Profiling , Genome, Viral/genetics , Open Reading Frames/genetics , Protein Biosynthesis , SARS-CoV-2/genetics , Viral Proteins/biosynthesis , Viral Proteins/genetics , Animals , Cell Line , Humans , Molecular Sequence Annotation , Peptides/genetics , Peptides/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Viral/genetics , RNA, Viral/metabolism , Ribosomes/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Viral Proteins/metabolism
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