Genome-wide single-cell and single-molecule footprinting of transcription factors with deaminase.

Decades of research have established that mammalian transcription factors (TFs) bind to each gene's regulatory regions and cooperatively control tissue specificity, timing, and intensity of gene transcription. Mapping the combination of TF binding sites genome wide is critically important for understanding functional genomics. Here, we report a technique to measure TFs' binding sites on the human genome with a near single-base resolution by footprinting with deaminase (FOODIE) on a single-molecule and single-cell basis.

Opposing, spatially-determined epigenetic forces impose restrictions on stochastic olfactory receptor choice.

Olfactory receptor (OR) choice represents an example of genetically hardwired stochasticity, where every olfactory neuron expresses one out of ~2000 OR alleles in the mouse genome in a probabilistic, yet stereotypic fashion. Here, we propose that topographic restrictions in OR expression are established in neuronal progenitors by two opposing forces: polygenic transcription and genomic silencing, both of which are influenced by dorsoventral gradients of transcription factors NFIA, B, and X. Polygenic transcription of OR genes may define spatially constrained OR repertoires, among which one OR allele is selected for singular expression later in development.

Single-cell bisulfite-free 5mC and 5hmC sequencing with high sensitivity and scalability.

Existing single-cell bisulfite-based DNA methylation analysis is limited by low DNA recovery, and the measurement of 5hmC at single-base resolution remains challenging. Here, we present a bisulfite-free single-cell whole-genome 5mC and 5hmC profiling technique, named Cabernet, which can characterize 5mC and 5hmC at single-base resolution with high genomic coverage. Cabernet utilizes Tn5 transposome for DNA fragmentation, which enables the discrimination between different alleles for measuring hemi-methylation status.

Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting.

The continuing emergence of SARS-CoV-2 variants highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by vaccination based on the ancestral (hereafter referred to as WT) strain would compromise the antibody response to Omicron-based boosters. Vaccination strategies to counter immune imprinting are critically needed.

Safety and Effectiveness of SA58 Nasal Spray Against COVID-19 Infection in Medical Personnel: An Open-Label, Blank-Controlled Study - Hohhot City, Inner Mongolia Autonomous Region, China, 2022.

What Is Already Known About This Topic?: The active ingredient of the SA58 Nasal Spray is a broad-spectrum neutralizing antibody with a high neutralizing capacity against different Omicron sub-variants in vitro studies.

What Is Added By This Report?: This study demonstrated the safety and effectiveness of SA58 Nasal Spray against coronavirus disease 2019 (COVID-19) infection in medical personnel for the first time.

What Are The Implications For Public Health Practice?: This study provides an effective approach for the public to reduce their risk of COVID-19 infection.

Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution.

Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA.5 (ref. ).

Correlated gene modules uncovered by high-precision single-cell transcriptomics.

Correlations in gene expression are used to infer functional and regulatory relationships between genes. However, correlations are often calculated across different cell types or perturbations, causing genes with unrelated functions to be correlated. Here, we demonstrate that correlated modules can be better captured by measuring correlations of steady-state gene expression fluctuations in single cells.

Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves that previous NAb drug screening strategies are deficient against the fast-evolving SARS-CoV-2. Better broad NAb drug candidate selection methods are needed. Here, we describe a rational approach for identifying RBD-targeting broad SARS-CoV-2 NAb cocktails.

Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75.

Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.

Circular RNA vaccines against SARS-CoV-2 and emerging variants.

As the emerging variants of SARS-CoV-2 continue to drive the worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report a circular RNA (circRNA) vaccine that elicited potent neutralizing antibodies and T cell responses by expressing the trimeric RBD of the spike protein, providing robust protection against SARS-CoV-2 in both mice and rhesus macaques. Notably, the circRNA vaccine enabled higher and more durable antigen production than the 1mΨ-modified mRNA vaccine and elicited a higher proportion of neutralizing antibodies and distinct Th1-skewed immune responses.

Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron.

The SARS-CoV-2 Omicron variant with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures of the spike (S) from Omicron reveals amino acid substitutions forging interactions that stably maintain an active conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of the viral fusion step.

Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies.

The SARS-CoV-2 B.1.1.

False Coronavirus Disease 2019 Cases due to Contamination by Inactivated Virus Vaccine.

A false-positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction result can lead to unnecessary public health measures. We report 2 individuals whose respiratory specimens were contaminated by an inactivated SARS-CoV-2 vaccine strain (CoronaVac), likely at vaccination premises. Incidentally, whole genome sequencing of CoronaVac showed adaptive deletions on the spike protein, which do not result in observable changes of antigenicity.

Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines.

SARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal domain (NTD). Here we report the humoral immune response to circulating SARS-CoV-2 variants, such as 501Y.V2 (B.