Vaccination with the tetravalent live-attenuated dengue virus (DENV) vaccines TV003 and TV005 causes a mild, relatively localized erythematous maculopapular skin rash in most dengue-naïve vaccinees. Human challenge model DENV strains, DENV2Δ30 and DENV3Δ30, trigger a confluent skin rash over most of the body in most unvaccinated participants. To determine the etiology of these rashes, we performed in situ hybridization for DENV genome and assessed cellular infiltration by H&E staining in skin biopsies from humans infected with live-attenuated dengue vaccine DENV2Δ30 or DENV3Δ30 challenge strains.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages of the Omicron variant rapidly became dominant in early 2022 and frequently cause human infections despite vaccination or prior infection with other variants. In addition to antibody-evading mutations in the receptor-binding domain, Omicron features amino acid mutations elsewhere in the Spike protein; however, their effects generally remain ill defined. The Spike D796Y substitution is present in all Omicron sub-variants and occurs at the same site as a mutation (D796H) selected during viral evolution in a chronically infected patient.
View Article and Find Full Text PDFThe COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Many vaccinated subjects are previously naive to SARS-CoV-2; however, almost all have previously encountered other coronaviruses (CoVs), and the role of this immunity in shaping the vaccine response remains uncharacterized. Here, we use longitudinal samples and highly multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes, in both phylogenetically conserved and non-conserved regions.
View Article and Find Full Text PDFThe COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Most vaccinated subjects are naïve to SARS-CoV-2, however almost all have previously encountered other coronaviruses (CoVs) and the role of this immunity in shaping the vaccine response remains uncharacterized. Here we use longitudinal samples and highly-multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes and in both phylogenetically conserved and non-conserved regions.
View Article and Find Full Text PDFPeroxiredoxins (PRDXs) catalyze the reduction of hydrogen peroxide (HO). PRDX4 is the only peroxiredoxin located within the endoplasmic reticulum (ER) and is the most highly expressed HO scavenger in the ER. PRDX4 has emerged as an important player in numerous diseases, such as fibrosis and metabolic syndromes, and its overoxidation is a potential indicator of ER redox stress.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
February 2020
Glutathione is a major redox buffer, reaching millimolar concentrations within cells and high micromolar concentrations in airways. While glutathione has been traditionally known as an antioxidant defense mechanism that protects the lung tissue from oxidative stress, glutathione more recently has become recognized for its ability to become covalently conjugated to reactive cysteines within proteins, a modification known as glutathionylation (or glutathiolation or protein mixed disulfide). glutathionylation has the potential to change the structure and function of the target protein, owing to its size (the addition of three amino acids) and charge (glutamic acid).
View Article and Find Full Text PDFAging is associated with enhanced oxidative stress and increased susceptibility to numerous diseases. This relationship is particularly striking with respect to the incidence of fibrotic lung disease. To identify potential mechanisms underlying the association between aging and susceptibility to fibrotic lung disease we analyzed transcriptome data from 342 disease-free human lung samples as a function of donor age.
View Article and Find Full Text PDFAntioxid Redox Signal
November 2019