The TLR7/8 agonist INI-4001 enhances the immunogenicity of a Powassan virus-like-particle vaccine.

Powassan virus (POWV) is a pathogenic tick-borne flavivirus that causes fatal neuroinvasive disease in humans. There are currently no approved therapies or vaccines for POWV infection. Here, we develop a POW virus-like particle (POW-VLP) based vaccine adjuvanted with the novel synthetic Toll-like receptor 7/8 agonist INI-4001.

Dissecting the biophysical mechanisms of oleate hydratase association with membranes.

This study investigates the dynamics of oleate hydratase (OhyA), a bacterial flavoenzyme from , and its interactions with lipid membranes, focusing on the factors influencing membrane binding and oligomerization. OhyA catalyzes the hydration of unsaturated fatty acids, playing a key role in bacterial pathogenesis by neutralizing host antimicrobial fatty acids. OhyA binds the membrane bilayer to access membrane-embedded substrates for catalysis, and structural studies have revealed that OhyA forms oligomers on membrane surfaces, stabilized by both protein-protein and protein-lipid interactions.

Independent evolution of oleate hydratase clades in Bacillales reflects molecular convergence.

Oleate hydratase (OhyA), a flavoenzyme that catalyzes the hydration of unsaturated fatty acids, has been identified in various Bacillales organisms, including those in the , , , and genera. In this study, we combine structural biology with molecular and phylogenetic analyses to investigate the evolutionary dynamics of the OhyA protein family within the Bacillales order. Our evolutionary analysis reveals two distinct OhyA clades (clade I and clade II) within Bacillales that, while sharing catalytic function, exhibit significant genomic and structural differences.

DDO-adjuvanted influenza A virus nucleoprotein mRNA vaccine induces robust humoral and cellular type 1 immune responses and protects mice from challenge.

A challenge in viral vaccine development is to produce vaccines that generate both neutralizing antibodies to prevent infection and cytotoxic CD8 T-cells that target conserved viral proteins and can eliminate infected cells to control virus spread. mRNA technology offers an opportunity to design vaccines based on conserved CD8-targeting epitopes, but achieving robust antigen-specific CD8 T-cells remains a challenge. Here, we tested the viral-derived oligonucleotide DDO268 as an adjuvant in the context of a model influenza A virus (IAV) nucleoprotein (NP) mRNA vaccine in C57BL/6 mice.

The TLR7/8 agonist INI-4001 enhances the immunogenicity of a Powassan virus-like-particle vaccine.

Powassan virus (POWV) is a pathogenic tick-borne flavivirus that causes fatal neuroinvasive disease in humans. There are currently no approved therapies or vaccines for POWV infection. Here, we develop a POW virus-like-particle (POW-VLP) based vaccine adjuvanted with the novel synthetic Toll-like receptor 7/8 agonist INI-4001.

DDO-adjuvanted influenza A virus nucleoprotein mRNA vaccine induces robust humoral and cellular type 1 immune responses and protects mice from challenge.

A challenge in viral vaccine development is to produce vaccines that generate both neutralizing antibodies to prevent infection and cytotoxic CD8 T-cells that target conserved viral proteins and can eliminate infected cells to control virus spread. mRNA vaccines offer an opportunity to design vaccines based on conserved CD8-targeting epitopes, but achieving robust antigen-specific CD8 T-cells remains a challenge. Here we tested the viral-derived oligonucleotide DDO268 as an adjuvant in the context of a model influenza A virus (IAV) nucleoprotein (NP) mRNA vaccine in C57BL/6 mice.

Spatial examination of social and environmental drivers of Middle East respiratory syndrome coronavirus (MERS-CoV) across Kenya.

Climate and agricultural land-use change has increased the likelihood of infectious disease emergence and transmissions, but these drivers are often examined separately as combined effects are ignored. Further, seldom are the influence of climate and agricultural land use on emerging infectious diseases examined in a spatially explicit way at regional scales. Our objective in this study was to spatially examine the climate, agriculture, and socio-demographic factors related to agro-pastoralism, and especially the combined effects of these variables that can influence the prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels across northern Kenya.

COVID-19 point-of-care tests can identify low-antibody individuals: In-depth immunoanalysis of boosting benefits in a healthy cohort.

The recommended COVID-19 booster vaccine uptake is low. At-home lateral flow assay (LFA) antigen tests are widely accepted for detecting infection during the pandemic. Here, we present the feasibility and potential benefits of using LFA-based antibody tests as a means for individuals to detect inadequate immunity and make informed decisions about COVID-19 booster immunization.

Corrigendum: Cross-reactive humoral and CD4 T cell responses to Mu and Gamma SARS-CoV-2 variants in a Colombian population.

[This corrects the article DOI: 10.3389/fimmu.2023.

The role of vaccination route with an adenovirus-vectored vaccine in protection, viral control, and transmission in the SARS-CoV-2/K18-hACE2 mouse infection model.

Introduction: Vaccination is the most effective mechanism to prevent severe COVID-19. However, breakthrough infections and subsequent transmission of SARS-CoV-2 remain a significant problem. Intranasal vaccination has the potential to be more effective in preventing disease and limiting transmission between individuals as it induces potent responses at mucosal sites.

Longitudinal Analysis of Humoral and Cellular Immune Response Following SARS-CoV-2 Vaccination Supports Utilizing Point-Of-Care Tests to Enhance COVID-19 Booster Uptake.

Unlabelled: Individuals with weaker neutralizing responses show reduced protection with SARS-CoV-2 variants. Booster vaccines are recommended for vaccinated individuals, but the uptake is low. We present the feasibility of utilizing point-of-care tests (POCT) to support evidence-based decision-making around COVID-19 booster vaccinations.

Metal coordinating inhibitors of Rift Valley fever virus replication.

Rift Valley fever virus (RVFV) is a veterinary and human pathogen and is an agent of bioterrorism concern. Currently, RVFV treatment is limited to supportive care, so new drugs to control RVFV infection are urgently needed. RVFV is a member of the order Bunyavirales, whose replication depends on the enzymatic activity of the viral L protein.

Infection order outweighs the role of CD4 T cells in tertiary flavivirus exposure.

The link between CD4 T and B cells during immune responses to DENV and ZIKV and their roles in cross-protection during heterologous infection is an active area of research. Here we used CD4 lymphocyte depletions to dissect the impact of cellular immunity on humoral responses during a tertiary flavivirus infection in macaques. We show that CD4 depletion in DENV/ZIKV-primed animals followed by DENV resulted in dysregulated adaptive immune responses.

Titration and neutralizing antibody quantification by focus forming assay for Powassan virus.

The development of high-throughput assays measuring Powassan virus (POWV) lineage I and II represents an important step in virological and immunological studies. By adapting focus-forming assays previously optimized for West Nile virus and Zika virus, this protocol is able to determine viral load, evaluate antivirals, and measure neutralizing antibodies. Although limited by its requirement of a detection antibody, this protocol includes a rapid and high-throughput assay for measuring viral titer.

Balanced T and B cell responses are required for immune protection against Powassan virus in virus-like particle vaccination.

Powassan virus (POWV) is a tick-borne pathogen for which humans are an incidental host. POWV infection can be fatal or result in long-term neurological sequelae; however, there are no approved vaccinations for POWV. Integral to efficacious vaccine development is the identification of correlates of protection, which we accomplished in this study by utilizing a murine model of POWV infection.

Roles of antiviral sensing and type I interferon signaling in the restriction of SARS-CoV-2 replication.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019. Few studies have compared replication dynamics and host responses to SARS-CoV-2 in cell lines from different tissues and species. Therefore, we investigated the role of tissue type and antiviral genes during SARS-CoV-2 infection in nonhuman primate (kidney) and human (liver, respiratory epithelial, gastric) cell lines.

The Ability of Zika virus Intravenous Immunoglobulin to Protect From or Enhance Zika Virus Disease.

The closely related flaviviruses, dengue and Zika, cause significant human disease throughout the world. While cross-reactive antibodies have been demonstrated to have the capacity to potentiate disease or mediate protection during flavivirus infection, the mechanisms responsible for this dichotomy are still poorly understood. To understand how the human polyclonal antibody response can protect against, and potentiate the disease in the context of dengue and Zika virus infection we used intravenous hyperimmunoglobulin (IVIG) preparations in a mouse model of the disease.

Obesity Enhances Disease Severity in Female Mice Following West Nile Virus Infection.

A rise in adiposity in the United States has resulted in more than 70% of adults being overweight or obese, and global obesity rates have tripled since 1975. Following the 2009 H1N1 pandemic, obesity was characterized as a risk factor that could predict severe infection outcomes to viral infection. Amidst the SARS-CoV-2 pandemic, obesity has remained a significant risk factor for severe viral disease as obese patients have a higher likelihood for developing severe symptoms and requiring hospitalization.

Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge.

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry. The current intramuscular vaccines elicit systemic immunity but not necessarily high-level mucosal immunity.

Selective estrogen receptor modulator, tamoxifen, inhibits Zika virus infection.

Zika virus (ZIKV) is an arbovirus belonging to the flaviviridae family with a risk assessment that has been increasing in recent years and was labeled a global health emergency by the World Health Organization in 2016. There are currently no Food and Drug Administration-approved treatment options available for ZIKV, so expeditious development of treatment options is urgent. To expedite this process, an on-market drug, tamoxifen (TAM), was selected as a promising candidate for repurposing due to its wide range of biological activities and because it has already been shown to possess activity against hepatitis C virus, a flavivirus in a separate genus.