Rapid Emergence of Potentially Transmissible Severe Acute Respiratory Syndrome Coronavirus 2 With Resistance to Combination Monoclonal Antibody Therapy.

Prolonged coronavirus disease 2019 may generate new viral variants. We report an immunocompromised patient treated with monoclonal antibodies who experienced rebound of viral RNA and emergence of an antibody-resistant (>1000-fold) variant containing 5 mutations in the spike gene. The mutant virus was isolated from respiratory secretions, suggesting the potential for secondary transmission.

Genetic Manipulation of Corynebacterium mastitidis to Better Understand the Ocular Microbiome.

Purpose: Corynebacterium spp. are Gram-positive bacteria commonly associated with the ocular surface. Corynebacterium mastitidis was isolated from mouse eyes and was demonstrated to induce a beneficial immune response that can protect the eye from pathogenic infection.

SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization.

Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (V ab6) that neutralizes all major variants including the recently emerged BA.1 and BA.

Potent and broad neutralization of SARS-CoV-2 variants of concern (VOCs) including omicron sub-lineages BA.1 and BA.2 by biparatopic human VH domains.

The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics with high neutralization breadth. Here, we characterized a human V domain, F6, which we generated by sequentially panning large phage-displayed V libraries against receptor binding domains (RBDs) containing VOC mutations. Cryo-EM analyses reveal that F6 has a unique binding mode that spans a broad surface of the RBD and involves the antibody framework region.

Xylose-Inducible Promoter Tools for Species and Their Use in Implicating a Role for the Type II Secretion System Protein XcpQ in the Inhibition of Corneal Epithelial Wound Closure.

Tunable control of gene expression is an invaluable tool for biological experiments. In this study, we describe a new xylose-inducible promoter system and evaluate it in both and The promoter, derived from the operon, was incorporated into a broad-host-range pBBR1-based plasmid and was compared to the -derived promoter using as a reporter. Green fluorescent protein (GFP) fluorescence from the promoter was inducible in both species, but not in , which may facilitate the cloning of genes toxic to to generate plasmids.

Herpes Simplex Virus 1-Specific CD8 T Cell Priming and Latent Ganglionic Retention Are Shaped by Viral Epitope Promoter Kinetics.

Reactivation of herpes simplex virus 1 (HSV-1) from neurons in sensory ganglia such as the trigeminal ganglia (TG) is influenced by virus-specific CD8 T cells that infiltrate the ganglia at the onset of latency and contract to a stable activated tissue-resident memory population. In C57BL/6 mice, half of HSV-specific CD8 T cells (gB-CD8s) recognize one dominant epitope (residues 498 to 505) on glycoprotein B (gB), while the remainder (non-gB-CD8s) recognize 19 subdominant epitopes from 12 viral proteins. To address how expression by HSV-1 influences the formation and ganglionic retention of CD8 T cell populations, we developed recombinant HSV-1 with the native immunodominant gB epitope disrupted but then expressed ectopically from different viral promoters.

Differential Expression of Immune Checkpoint Molecules on CD8 T Cells Specific for Immunodominant and Subdominant Herpes Simplex Virus 1 Epitopes.

Herpes simplex virus 1 (HSV-1) causes a lifelong infection of neurons that innervate barrier sites like the skin and mucosal surfaces like the eye. After primary infection of the cornea, the virus enters latency within the trigeminal ganglion (TG), from which it can reactivate throughout the life of the host. Viral latency is maintained, in part, by virus-specific CD8 T cells that nonlethally interact with infected neurons.

Influence of an immunodominant herpes simplex virus type 1 CD8+ T cell epitope on the target hierarchy and function of subdominant CD8+ T cells.

Herpes simplex virus type 1 (HSV-1) latency in sensory ganglia such as trigeminal ganglia (TG) is associated with a persistent immune infiltrate that includes effector memory CD8+ T cells that can influence HSV-1 reactivation. In C57BL/6 mice, HSV-1 induces a highly skewed CD8+ T cell repertoire, in which half of CD8+ T cells (gB-CD8s) recognize a single epitope on glycoprotein B (gB498-505), while the remainder (non-gB-CD8s) recognize, in varying proportions, 19 subdominant epitopes on 12 viral proteins. The gB-CD8s remain functional in TG throughout latency, while non-gB-CD8s exhibit varying degrees of functional compromise.

Subclinical Herpes Simplex Virus Type 1 Infections Provide Site-Specific Resistance to an Unrelated Pathogen.

HSV-1 infections of the cornea range in severity from minor transient discomfort to the blinding disease herpes stromal keratitis, yet most patients experience a single episode of epithelial keratitis followed by re-establishment of a clear cornea. We asked whether a single transient episode of HSV-1 epithelial keratitis causes long-term changes in the corneal microenvironment that influence immune responses to subsequent corneal infection or trauma. We showed that C57BL/6 mouse corneas infected with HSV-1 KOS, which induces transient herpes epithelial keratitis without herpes stromal keratitis sequelae, possessed a significant leukocytic infiltrate composed primarily of CD4 T cells and macrophages along with elevated chemokines and cytokines that persisted without loss of corneal clarity (subclinical inflammation).