Isolation of human antibodies against influenza B neuraminidase and mechanisms of protection at the airway interface.

Influenza B viruses (IBVs) comprise a substantial portion of the circulating seasonal human influenza viruses. Here, we describe the isolation of human monoclonal antibodies (mAbs) that recognized the IBV neuraminidase (NA) glycoprotein from an individual following seasonal vaccination. Competition-binding experiments suggested the antibodies recognized two major antigenic sites.

Treatment of highly virulent mammarenavirus infections-status quo and future directions.

Introduction: Mammarenaviruses are negative-sense bisegmented enveloped RNA viruses that are endemic in Africa, the Americas, and Europe. Several are highly virulent, causing acute human diseases associated with high case fatality rates, and are considered to be significant with respect to public health impact or bioterrorism threat.

Areas Covered: This review summarizes the status quo of treatment development, starting with drugs that are in advanced stages of evaluation in early clinical trials, followed by promising candidate medical countermeasures emerging from bench analyses and investigational animal research.

Influenza virus immune imprinting dictates the clinical outcomes in ferrets challenged with highly pathogenic avian influenza virus H5N1.

Zoonotic transmission of H5N1 highly pathogenic avian influenza virus (HPAIV) into the human population is an increasing global threat. The recent 2022 HPAIV outbreak significantly highlighted this possibility, increasing concern in the general population. The clinical outcomes of H5N1 influenza virus exposure can be determined by an individual's primary influenza virus infection (imprinting) or vaccination status.

MVA vector expression of SARS-CoV-2 spike protein and protection of adult Syrian hamsters against SARS-CoV-2 challenge.

Numerous vaccine candidates against SARS-CoV-2, the causative agent of the COVID-19 pandemic, are under development. The majority of vaccine candidates to date are designed to induce immune responses against the viral spike (S) protein, although different forms of S antigen have been incorporated. To evaluate the yield and immunogenicity of different forms of S, we constructed modified vaccinia virus Ankara (MVA) vectors expressing full-length S (MVA-S), the RBD, and soluble S ectodomain and tested their immunogenicity in dose-ranging studies in mice.

Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections.

H5N1 COBRA hemagglutinin (HA) sequences, termed human COBRA-2 HA, were constructed through layering of HA sequences from viruses isolated from humans collected between 2004-2007 using only clade 2 strains. These COBRA HA proteins, when expressed on the surface of virus-like particles (VLP), elicited protective immune responses in mice, ferrets, and non-human primates. However, these vaccines were not as effective at inducing neutralizing antibodies against newly circulating viruses.

SARS-CoV-2 B.1.1.7 Infection of Syrian Hamster Does Not Cause More Severe Disease, and Naturally Acquired Immunity Confers Protection.

Epidemiological studies have revealed the emergence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC), including the lineage B.1.1.

Efficacy of recombinant Marek's disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses.

The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.

SARS-CoV-2 infection induces protective immunity and limits transmission in Syrian hamsters.

A critical question in understanding the immunity to SARS-COV-2 is whether recovered patients are protected against re-challenge and transmission upon second exposure. We developed a Syrian hamster model in which intranasal inoculation of just 100 TCID virus caused viral pneumonia. Aged hamsters developed more severe disease and even succumbed to SARS-CoV-2 infection, representing the first lethal model using genetically unmodified laboratory animals.

Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses.

Highly pathogenic H5N1 influenza viruses continue to spread around the globe and reassort with low pathogenic avian influenza viruses often resulting in morbidity and mortality to not only waterfowl, but also poultry. Our group previously developed two hemagglutinin (HA) based vaccines using a methodology termed computationally optimized broadly reactive antigen (COBRA). Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.

Structural and antigenic characterization of a computationally-optimized H5 hemagglutinin influenza vaccine.

Influenza A virus is a leading cause of death worldwide. Viruses of the H5 subtype have the potential to induce high mortality, and no vaccines are currently available to protect against H5 influenza viruses in the event of an outbreak. Experimental vaccination with one clade 2 virus does not protect against other subclades.

Parainfluenza virus 5 (PIV5) amplifying virus-like particles expressing respiratory syncytial virus (RSV) antigens protect mice against RSV infection.

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in children under one year of age. In addition to causing severe respiratory diseases in children, it is also a major cause of morbidity and mortality among the elderly and immunocompromised individuals. RSV is the most common cause of lower respiratory tract infections, yet there are currently no licensed vaccines.

A review of H5Nx avian influenza viruses.

Highly pathogenic avian influenza viruses (HPAIVs), originating from the A/goose/Guangdong/1/1996 H5 subtype, naturally circulate in wild-bird populations, particularly waterfowl, and often spill over to infect domestic poultry. Occasionally, humans are infected with HPAVI H5N1 resulting in high mortality, but no sustained human-to-human transmission. In this review, the replication cycle, pathogenicity, evolution, spread, and transmission of HPAIVs of H5Nx subtypes, along with the host immune responses to Highly Pathogenic Avian Influenza Virus (HPAIV) infection and potential vaccination, are discussed.

Impact of age and pre-existing influenza immune responses in humans receiving split inactivated influenza vaccine on the induction of the breadth of antibodies to influenza A strains.

Most humans have pre-existing immunity to influenza viruses. In this study, volunteers (ages of 18-85 years) were vaccinated with split, inactivated Fluzone™ influenza vaccine in four consecutive influenza seasons from 2013 to 2016 seasons. The impact of repeated vaccination on breadth and durability of antibodies was assessed as a result of vaccine strain changes.

Traumatic Brain Injury Causes Endothelial Dysfunction in the Systemic Microcirculation through Arginase-1-Dependent Uncoupling of Endothelial Nitric Oxide Synthase.

Endothelial dysfunction is a hallmark of many chronic diseases, including diabetes and long-term hypertension. We show that acute traumatic brain injury (TBI) leads to endothelial dysfunction in rat mesenteric arteries. Endothelial-dependent dilation was greatly diminished 24 h after TBI because of impaired nitric oxide (NO) production.

Molecular mechanisms underlying skeletal muscle weakness in human cancer: reduced myosin-actin cross-bridge formation and kinetics.

Many patients with cancer experience physical disability following diagnosis, although little is known about the mechanisms underlying these functional deficits. To characterize skeletal muscle adaptations to cancer in humans, we evaluated skeletal muscle structure and contractile function at the molecular, cellular, whole-muscle, and whole-body level in 11 patients with cancer (5 cachectic, 6 noncachectic) and 6 controls without disease. Patients with cancer showed a 25% reduction in knee extensor isometric torque after adjustment for muscle mass (P < 0.