Assessment of CD8 T-cell mediated immunity in an influenza A(H3N2) human challenge model in Belgium: a single centre, randomised, double-blind phase 2 study.

Background: Protection afforded by inactivated influenza vaccines can theoretically be improved by inducing T-cell responses to conserved internal influenza A antigens. We assessed whether, in an influenza controlled human infection challenge, susceptible individuals receiving a vaccine boosting T-cell responses would exhibit lower viral load and decreased symptoms compared with placebo recipients.

Methods: In this single centre, randomised, double-blind phase 2 study, healthy adult (aged 18-55 years) volunteers with microneutralisation titres of less than 20 to the influenza A(H3N2) challenge strain were enrolled at an SGS quarantine facility in Antwerp, Belgium.

Efficacy of a monovalent (D614) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, multi-country study.

Background: The literature on first generation COVID-19 vaccines show they were less effective against new SARS-CoV-2 variants of concern including Omicron (BA.1, BA.2, BA.

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, parallel, randomised, modified double-blind, placebo-controlled trial.

Background: COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern. This study aimed to describe the clinical efficacy and safety of a bivalent SARS-CoV-2 recombinant protein vaccine as a two-injection primary series during a period of circulation of the omicron (B.1.

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 Protein Vaccine.

Background: COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern.

Methods: We conducted a global Phase 3, multi-stage efficacy study (NCT04904549) among adults aged ≥18 years. Participants were randomized 1:1 to receive two intramuscular injections 21 days apart of a bivalent SARS-CoV-2 recombinant protein vaccine with AS03-adjuvant (5 μg of ancestral (D614) and 5 μg of B.

Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S.

Background: The Ad26.COV2.S vaccine was highly effective against severe-critical coronavirus disease 2019 (Covid-19), hospitalization, and death in the primary phase 3 efficacy analysis.

Safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein vaccine (CoV2 preS dTM) in healthy adults: interim findings from a phase 2, randomised, dose-finding, multicentre study.

Background: We evaluated our SARS-CoV-2 prefusion spike recombinant protein vaccine (CoV2 preS dTM) with different adjuvants, unadjuvanted, and in a one-injection and two-injection dosing schedule in a previous phase 1-2 study. Based on interim results from that study, we selected a two-injection schedule and the AS03 adjuvant for further clinical development. However, lower than expected antibody responses, particularly in older adults, and higher than expected reactogenicity after the second vaccination were observed.

Examination of the interaction between age-specific predation and chronic disease in the Greater Yellowstone Ecosystem.

Predators may create healthier prey populations by selectively removing diseased individuals. Predators typically prefer some ages of prey over others, which may, or may not, align with those prey ages that are most likely to be diseased. The interaction of age-specific infection and predation has not been previously explored and likely has sizable effects on disease dynamics.

Broadly Reactive IgG Responses to Heterologous H5 Prime-Boost Influenza Vaccination Are Shaped by Antigenic Relatedness to Priming Strains.

Prime-boost vaccinations of humans with different H5 strains have generated broadly protective antibody levels. However, the effect of an individual's H5 exposure history on antibody responses to subsequent H5 vaccination is poorly understood. To investigate this, we analyzed the IgG responses to H5 influenza A/Indonesia/5/2005 (Ind05) virus vaccination in three cohorts: (i) a doubly primed group that had received two H5 virus vaccinations, namely, against influenza A/Vietnam/203/2004 (Vie04) virus 5 years prior and A/Hong Kong/156/1997 (HK97) 11 years prior to the Ind05 vaccination; (ii) a singly primed group that had received a vaccination against Vie04 virus 5 years prior to the Ind05 vaccination; and (iii) an H5-naive group that received two doses of the Ind05 vaccine 28 days apart.

Social networks based on frequency of roost cohabitation do not reflect association rates of within their roosts.

Bats are a group of mammals well known for forming dynamic social groups. Studies of bat social structures are often based upon the frequency at which bats occupy the same roosts because observing bats directly is not always possible. However, it is not always clear how closely bats occupying the same roost associate with each other, obscuring whether associations result from social relationships or factors such as shared preferences for roosts.

Prevalence of Mycoplasma spp. in the Respiratory Tract of Healthy North American Bison (Bison bison) and Comparison with Serum Antibody Status.

Mycoplasma bovis is a primary cause of respiratory and reproductive diseases in North American bison (Bison bison), with significant morbidity and mortality. The epidemiology of M. bovis in bison is poorly understood, hindering efforts to develop effective control measures.

Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19.

Background: The Ad26.COV2.S vaccine is a recombinant, replication-incompetent human adenovirus type 26 vector encoding full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in a prefusion-stabilized conformation.

Adjuvanted recombinant hemagglutinin H7 vaccine to highly pathogenic influenza A(H7N9) elicits high and sustained antibody responses in healthy adults.

An unprecedented number of human infections with avian influenza A(H7N9) in the fifth epidemic wave during the winter of 2016-2017 in China and their antigenic divergence from the viruses that emerged in 2013 prompted development of updated vaccines for pandemic preparedness. We report on the findings of a clinical study in healthy adults designed to evaluate the safety and immunogenicity of three dose levels of recombinant influenza vaccine derived from highly pathogenic A/Guangdong/17SF003/2016 (H7N9) virus adjuvanted with AS03 or MF59 oil-in water emulsions. Most of the six study groups meet the FDA CBER-specified vaccine licensure criterion of 70% seroprotection rate (SPR) for hemagglutination inhibition antibodies to the homologous virus.

Improving pandemic preparedness through better, faster influenza vaccines.

. Timely availability of effective influenza vaccine will be critical to mitigate the next influenza pandemic. The mission of Biomedical Advanced Research and Development Authority (BARDA) is to develop medical countermeasures against pandemics, including influenza and other health security threats.

Gaps in Serologic Immunity against Contemporary Swine-Origin Influenza A Viruses among Healthy Individuals in the United States.

Influenza A Viruses (IAV) in domestic swine (IAV-S) are associated with sporadic zoonotic transmission at the human-animal interface. Previous pandemic IAVs originated from animals, which emphasizes the importance of characterizing human immunity against the increasingly diverse IAV-S. We analyzed serum samples from healthy human donors ( = 153) using hemagglutination-inhibition (HAI) assay to assess existing serologic protection against a panel of contemporary IAV-S isolated from swine in the United States ( = 11).

Serological evidence for historical and present-day exposure of North American bison to Mycoplasma bovis.

Background: Mycoplasma bovis causes mastitis, otitis, pneumonia and arthritis in cattle and is a major contributor to bovine respiratory disease complex. Around the year 2000, it emerged as a significant threat to the health of North American bison. Whether healthy bison are carriers of M.

A Mutated PB1 Residue 319 Synergizes with the PB2 N265S Mutation of the Live Attenuated Influenza Vaccine to Convey Temperature Sensitivity.

Current influenza vaccines have modest efficacy. This is especially true for current live attenuated influenza vaccines (LAIV), which have been inferior to the inactivated versions in recent years. Therefore, a new generation of live vaccines may be needed.

Viewpoint of a WHO Advisory Group Tasked to Consider Establishing a Closely-monitored Challenge Model of Coronavirus Disease 2019 (COVID-19) in Healthy Volunteers.

WHO convened an Advisory Group (AG) to consider the feasibility, potential value, and limitations of establishing a closely-monitored challenge model of experimental severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) in healthy adult volunteers. The AG included experts in design, establishment, and performance of challenges. This report summarizes issues that render a COVID-19 model daunting to establish (the potential of SARS-CoV-2 to cause severe/fatal illness, its high transmissibility, and lack of a "rescue treatment" to prevent progression from mild/moderate to severe clinical illness) and it proffers prudent strategies for stepwise model development, challenge virus selection, guidelines for manufacturing challenge doses, and ways to contain SARS-CoV-2 and prevent transmission to household/community contacts.

A phase 2 study of the bivalent VLP norovirus vaccine candidate in older adults; impact of MPL adjuvant or a second dose.

Introduction: Acute norovirus gastroenteritis causes significant morbidity and in uncommon cases fatality in older adults. We investigated the safety and immunogenicity of bivalent virus-like particle (VLP) vaccine candidate formulations with and without monophosphoryl lipid A (adjuvant MPL) in this population.

Methods: In this phase II, double-blind, controlled trial 294 healthy adults, ≥ 60 years of age, were randomized (1:1:1:1) to four groups to receive one or two intramuscular immunizations 28 days apart, with 26 18-49 year-old controls who received one MPL-free dose.

Characterizing Emerging Canine H3 Influenza Viruses.

The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk.

Evidence That Blunted CD4 T-Cell Responses Underlie Deficient Protective Antibody Responses to Influenza Vaccines in Repeatedly Vaccinated Human Subjects.

Despite the benefits of yearly influenza vaccination, accumulating evidence suggests that diminished vaccine efficacy may be related to repeated vaccination. Although studied at the level of B-cell responses, CD4 T-cell responses have not yet been examined. In this study, we analyze CD4 T-cell responses to influenza vaccination in subjects who differ in their vaccine history.

Monoclonal Antibody Responses after Recombinant Hemagglutinin Vaccine versus Subunit Inactivated Influenza Virus Vaccine: a Comparative Study.

Vaccination is the best measure of protection against influenza virus infection. Vaccine-induced antibody responses target mainly the hemagglutinin (HA) surface glycoprotein, composed of the head and the stalk domains. Recently two novel vaccine platforms have been developed for seasonal influenza vaccination: a recombinant HA vaccine produced in insect cells (Flublok) and Flucelvax, prepared from virions produced in mammalian cells.

Repeat vaccination reduces antibody affinity maturation across different influenza vaccine platforms in humans.

Several vaccines are approved in the United States for seasonal influenza vaccination every year. Here we compare the impact of repeat influenza vaccination on hemagglutination inhibition (HI) titers, antibody binding and affinity maturation to individual hemagglutinin (HA) domains, HA1 and HA2, across vaccine platforms. Fold change in HI and antibody binding to HA1 trends higher for H1N1pdm09 and H3N2 but not against B strains in groups vaccinated with FluBlok compared with FluCelvax and Fluzone.

Continuous Readout versus Titer-Based Assays of Influenza Vaccine Trials: Sensitivity, Specificity, and False Discovery Rates.

The current gold standard for measuring antibody-based immunity to influenza viruses relies on the hemagglutinin inhibition assay (HAI), an 80-year-old technology, and the microneutralization assay (MN). Both assays use serial dilution to provide a discrete, ranked readout of 8-14 categorical titer values for each sample. In contrast to other methods of measuring vaccine antibody levels that produce a continuous readout (i.

Improved Specificity and False Discovery Rates for Multiplex Analysis of Changes in Strain-Specific Anti-Influenza IgG.

We describe a statistical approach to compare absolute antibody concentrations, both within and across subjects, derived from a multidimensional measurement of IgG binding to the influenza surface receptor hemagglutinin (HA). This approach addresses a fundamental problem in the field of vaccine immunology: how to accurately compare the levels of antibodies against multiple influenza strains. The mPlex-Flu assay can simultaneously measure the concentration of IgG antibodies against up to 50 influenza strains with only ≤10   of serum.