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The SARS-CoV-2 Omicron variant is more immune evasive and less virulent than other major viral variants that have so far been recognized 1-12 . The Omicron spike (S) protein, which has an unusually large number of mutations, is considered to be the main driver of these phenotypes. Here we generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron (BA.1 lineage) in the backbone of an ancestral SARS-CoV-2 isolate, and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escaped vaccine-induced humoral immunity, mainly owing to mutations in the receptor-binding motif; however, unlike naturally occurring Omicron, it efficiently replicated in cell lines and primary-like distal lung cells. Similarly, in K18-hACE2 mice, although virus bearing Omicron S caused less severe disease than the ancestral virus, its virulence was not attenuated to the level of Omicron. Further investigation showed that mutating non-structural protein 6 (nsp6) in addition to the S protein was sufficient to recapitulate the attenuated phenotype of Omicron. This indicates that although the vaccine escape of Omicron is driven by mutations in S, the pathogenicity of Omicron is determined by mutations both in and outside of the S protein., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Monoclonal antibodies (mAbs) play an important role in diagnostics and therapy of infectious diseases. Here we utilize a single-particle interferometric reflectance imaging sensor (SP-IRIS) for screening 30 mAbs against Ebola, Sudan, and Lassa viruses (EBOV, SUDV, and LASV) to find out the ideal capture antibodies for whole virus detection using recombinant vesicular stomatitis virus (rVSV) models expressing surface glycoproteins (GPs) of EBOV, SUDV, and LASV. We also make use of the binding properties on SP-IRIS to develop a model for mapping the antibody epitopes on the GP structure. mAbs that bind to mucin-like domain or glycan cap of the EBOV surface GP show the highest signal on SP-IRIS, followed by mAbs that target the GP1-GP2 interface at the base domain. These antibodies were shown to be highly efficacious against EBOV infection in non-human primates in previous studies. For LASV detection, 8.9F antibody showed the best performance on SP-IRIS. This antibody binds to a unique region on the surface GP compared to other 15 mAbs tested. In addition, we demonstrate a novel antibody competition assay using SP-IRIS and rVSV-EBOV models to reveal the competition between mAbs in three successful therapeutic mAb cocktails against EBOV infection. We provide an explanation as to why ZMapp cocktail has higher efficacy compared to the other two cocktails by showing that three mAbs in this cocktail (13C6, 2G4, 4G7) do not compete with each other for binding to EBOV GP. In fact, the binding of 13C6 enhances the binding of 2G4 and 4G7 antibodies. Our results establish SP-IRIS as a versatile tool that can provide high-throughput screening of mAbs, multiplexed and sensitive detection of viruses, and evaluation of therapeutic antibody cocktails., (© 2023. The Author(s).)

Background: Coronavirus disease 2019 (COVID-19) is a pandemic that has and will continue to affect many pregnant women. Knowledge regarding the risk of vertical transmission is limited. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs typically have been used to confirm the diagnosis among infants, but whether the virus can be detected in other biological specimens, and therefore potentially transmitted in other ways, is unknown. Positive SARS-CoV-2 RT-PCR has been reported from feces and urine from adult patients. We hypothesize that the presence of SARS-CoV-2 in infant urine and fecal samples after prenatal COVID-19 exposure is low., Methods: We examined the presence of SARS-CoV-2 RNA using RT-PCR in urine and fecal samples among 42 infants born to SARS-CoV-2-infected mothers during different stages of pregnancy., Results: A urine sample was collected from 39 of 42 infants and fecal samples from all 42 infants shortly after birth. Although the majority of the women had the symptomatic disease (85.6%), we were unable to detect the presence of SARS-CoV-2 virus from any infant urine or fecal samples., Conclusions: SARS-CoV-2 was not detected in infant urine or feces after maternal infection during pregnancy, providing further evidence for low rates of perinatal transmission., Impact: SARS-CoV-2 was not detected in the urine or feces of infants of mothers with COVID-19 during various time points in pregnancy. This study provides further evidence for low rates of perinatal transmission of SARS-CoV-2. Results help to provide guidance on perinatal care practices for infants exposed to COVID-19 in utero., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Ebola virus disease (EVD) is a serious illness with mortality rates of 20-90% in various outbreaks. EVD is characterized by robust virus replication and strong host inflammatory response. Analyzing host immune responses has increasingly involved multimodal approaches including transcriptomics to profile gene expression. We studied cynomolgus macaques exposed to Ebola virus Makona via different routes with the intent of comparing RNA-Seq to a NanoString nCounter codeset targeting 769 non-human primate (NHP) genes. RNA-Seq analysis of serial blood samples showed different routes led to the same overall transcriptional response seen in previously reported EBOV-exposed NHP studies. Both platforms displayed a strong correlation in gene expression patterns, including a strong induction of innate immune response genes at early times post-exposure, and neutrophil-associated genes at later time points. A 41-gene classifier was tested in both platforms for ability to cluster samples by infection status. Both NanoString and RNA-Seq could be used to predict relative abundances of circulating immune cell populations that matched traditional hematology. This demonstrates the complementarity of RNA-Seq and NanoString. Moreover, the development of an NHP-specific NanoString codeset should augment studies of filoviruses and other high containment infectious diseases without the infrastructure requirements of RNA-Seq technology.

Synaptic plasticity is thought to be a key process for learning, memory and other cognitive functions of the nervous system. The initial events of plasticity require the conversion of brief electrical signals into alterations of the biochemical properties of synapses that last for much longer than the initial stimuli. Here we show that a regulator of synaptic plasticity, calcium/calmodulin-dependent protein kinase IIalpha (CaMKII), sequentially translocates to postsynaptic sites, undergoes autophosphorylation and gets trapped for several minutes until its dissociation is induced by secondary autophosphorylation and phosphatase 1 action. Once dissociated, CaMKII shows facilitated translocation for several minutes. This suggests that trapping of CaMKII by its targets and priming of CaMKII translocation may function as biochemical memory mechanisms that change the signaling capacity of synapses.