Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity

SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S, and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild-type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the FDA, and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics

Comparative analysis of spike-specific IgG Fc glycoprofiles elicited by adenoviral, mRNA, and protein-based SARS-CoV-2 vaccines

Summary: IgG antibodies are important mediators of vaccine-induced immunity through complement- and Fc receptor-dependent effector functions. Both are influenced by the composition of the conserved N-linked glycan located in the IgG Fc domain. Here, we compared the anti-Spike (S) IgG1 Fc glycosylation profiles in response to mRNA, adenoviral, and protein-based COVID-19 vaccines by mass spectrometry (MS). All vaccines induced a transient increase of antigen-specific IgG1 Fc galactosylation and sialylation. An initial, transient increase of afucosylated IgG was induced by membrane-encoding S protein formulations. A fucose-sensitive ELISA for antigen-specific IgG (FEASI) exploiting FcγRIIIa affinity for afucosylated IgG was used as an orthogonal method to confirm the LC-MS-based afucosylation readout. Our data suggest that vaccine-induced anti-S IgG glycosylation is dynamic, and although variation is seen between different vaccine platforms and individuals, the evolution of glycosylation patterns display marked overlaps

Tectono-Stratigraphic Evolution of the Atuel Depocenter During the Late Triassic to Early Jurassic Rift Stage, Neuquén Basin, West-Central Argentina

The Neuquén basin presents an almost continuous record from the Late Triassic until the Paleocene,making it an excellent case study of the most relevant tectonic stages of southern South America during the Mesozoic. It was initiated in the Late Triassic to Early Jurassic times as a continental rift basin in the context of a widespread extensional stage that affected western Gondwana andculminated with the break-up of the supercontinent.The Atuel depocenter is located in the northern sector of the Neuquén basin. Synrift and sag units are represented by Upper Triassic to Lower Jurassic siliciclastic marine and continental sedimentary rocks including the oldest marine deposits of the basin, of Late Triassic age. The depocenter infill hasbeen deformed and exhumed during the Andean orogeny, being presently exposed in the northern sector of the Malargüe fold and thrust belt. In this review, we have integrated a large set of stratigraphic, sedimentologic, geochronologic and structural data in order to unravel the tectono-sedimentary evolution of the Atuel depocenter, and to evaluate the main controlling factors of thesynrift stage. We analyzed data from the synrift units, such as facies and thickness distribution, sandstone provenance, detrital zircon geochronology data, kinematic data from outcrop scale normal faults, angular and progressive unconformities and subsurface information. Reactivation of preexisting NNW-striking anisotropies under a regional NNE extension resulted in anoblique rift setting, which generated a bimodal distribution of NNW- and WNW-striking major normal faults. Strain and stress tensors obtained from the kinematic and dynamic analysis of structural data show a complex heterogeneity that we interpreted as a result of local stress permutations due to both activity of the larger faults, and to strain partitioning inside the Atueldepocenter.Sedimentologic and petrographic data revealed a complex evolution with strong lateral variations of the depositional environments during the synrift phase, which lasted from Rhaetian to Pliensbachian times. We identified several stages that were controlled by processes of initiation, propagation, growth, linkage and deactivation of new and reactivated faults along the depocenter evolution, in combination with sea level changes related to global eustatic variations. Sandstone provenance data suggest that an important basin reorganization by the Toarcian, probably related to the initiation of the sag stage in this depocenter.Fil: Bechis, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Diversidad Cultural y Procesos de Cambio. Universidad Nacional de Río Negro. Instituto de Investigaciones en Diversidad Cultural y Procesos de Cambio; ArgentinaFil: Giambiagi, Laura Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla; ArgentinaFil: Tunik, Maisa Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Suriano, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla; ArgentinaFil: Lanés, Silvia. Cape Town; SudáfricaFil: Mescua, Jose Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla; Argentina. Universidad Nacional de Cuyo; Argentin