Enhanced isolation of influenza viruses in qualified cells improves the probability of well-matched vaccines.

Influenza vaccines are utilised to combat seasonal and pandemic influenza. The key to influenza vaccination currently is the availability of candidate vaccine viruses (CVVs). Ideally, CVVs reflect the antigenic characteristics of the circulating virus, which may vary depending upon the isolation method.

Impact of prior vaccination on antibody response and influenza-like illness among Australian healthcare workers after influenza vaccination in 2016.

Background: Epidemiological studies suggest that influenza vaccine effectiveness decreases with repeated administration. We examined antibody responses to influenza vaccination among healthcare workers (HCWs) by prior vaccination history and determined the incidence of influenza infection.

Methods: HCWs were vaccinated with the 2016 Southern Hemisphere quadrivalent influenza vaccine.

Immune cellular networks underlying recovery from influenza virus infection in acute hospitalized patients.

How innate and adaptive immune responses work in concert to resolve influenza disease is yet to be fully investigated in one single study. Here, we utilize longitudinal samples from patients hospitalized with acute influenza to understand these immune responses. We report the dynamics of 18 important immune parameters, related to clinical, genetic and virological factors, in influenza patients across different severity levels.

Which influenza viruses will emerge following the SARS-CoV-2 pandemic?

The world has experienced five pandemics in just over one hundred years, four due to influenza and one due to coronavirus (SARS-CoV-2). In each case of pandemic influenza, the pandemic influenza strain has replaced the previous seasonal influenza virus. Notably, throughout the SARS-CoV-2 pandemic, there has been a 99% reduction in influenza isolation globally.

New Technologies for Influenza Vaccines.

Vaccine development has been hampered by the long lead times and the high cost required to reach the market. The 2020 pandemic, caused by a new coronavirus (SARS-CoV-2) that was first reported in late 2019, has seen unprecedented rapid activity to generate a vaccine, which belies the traditional vaccine development cycle. Critically, much of this progress has been leveraged off existing technologies, many of which had their beginnings in influenza vaccine development.

Immunogenicity of the inactivated influenza vaccine in children who have undergone allogeneic haematopoietic stem cell transplant.

Influenza vaccination is recommended for children following allogeneic haematopoietic stem cell transplant (HSCT), however there is limited evidence regarding its benefit. A prospective multicentre study was conducted to evaluate the immunogenicity of the inactivated influenza vaccine in children who have undergone HSCT compared with healthy age-matched controls. Participants were vaccinated between 2013 and 2016 according to Australian guidelines.

Influenza A Virus Infection Induces Viral and Cellular Defective Ribosomal Products Encoded by Alternative Reading Frames.

The importance of antiviral CD8 T cell recognition of alternative reading frame (ARF)-derived peptides is uncertain. In this study, we describe an epitope (NS1-ARF2) present in a predicted 14-residue peptide encoded by the +1 register of NS1 mRNA in the influenza A virus (IAV). NS1-ARF2 elicits a robust, highly functional CD8 T cell response in IAV-infected BALB/c mice.

Safety, immunogenicity and protection of A(H3N2) live attenuated influenza vaccines containing wild-type nucleoprotein in a ferret model.

Live attenuated influenza vaccines (LAIVs) are promising tools for the induction of broad protection from influenza due to their ability to stimulate cross-reactive T cells against influenza pathogens. One of the major targets for cytotoxic T-cell immunity is viral nucleoprotein (NP), which is relatively conserved among antigenically distant influenza viruses. Nevertheless, a diversity of epitope composition has been found in the NP protein of different lineages of influenza A viruses.

Investigating Viral Interference Between Influenza A Virus and Human Respiratory Syncytial Virus in a Ferret Model of Infection.

Epidemiological studies have observed that the seasonal peak incidence of influenza virus infection is sometimes separate from the peak incidence of human respiratory syncytial virus (hRSV) infection, with the peak incidence of hRSV infection delayed. This is proposed to be due to viral interference, whereby infection with one virus prevents or delays infection with a different virus. We investigated viral interference between hRSV and 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) in the ferret model.

Circulating T cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity.

Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infections. IIV activates B cells and T follicular helper (T) cells and thus engenders antibody-secreting cells and serum antibody titers. However, the cellular events preceding generation of protective immunity in humans are inadequately understood.

Evidence for Viral Interference and Cross-reactive Protective Immunity Between Influenza B Virus Lineages.

Background: Two influenza B virus lineages, B/Victoria and B/Yamagata, cocirculate in the human population. While the lineages are serologically distinct, cross-reactive responses to both lineages have been detected. Viral interference describes the situation whereby infection with one virus limits infection and replication of a second virus.

Pathogenesis, Humoral Immune Responses, and Transmission between Cohoused Animals in a Ferret Model of Human Respiratory Syncytial Virus Infection.

Small-animal models have been used to obtain many insights regarding the pathogenesis and immune responses induced following infection with human respiratory syncytial virus (hRSV). Among those described to date, infections in cotton rats, mice, guinea pigs, chinchillas, and Syrian hamsters with hRSV strains Long and/or A2 have been well characterized, although clinical isolates have also been examined. Ferrets are also susceptible to hRSV infection, but the pathogenesis and immune responses elicited following infection have not been well characterized.

Influenza vaccination responses: Evaluating impact of repeat vaccination among health care workers.

Objective: To compare the antibody response to influenza between health care workers (HCWs) who have received multiple vaccinations (high vaccination group) and those who have received fewer vaccinations (low vaccination group).

Design: Prospective serosurvey.

Setting: Tertiary referral hospital.

Modelling cross-reactivity and memory in the cellular adaptive immune response to influenza infection in the host.

The cellular adaptive immune response plays a key role in resolving influenza infection. Experiments where individuals are successively infected with different strains within a short timeframe provide insight into the underlying viral dynamics and the role of a cross-reactive immune response in resolving an acute infection. We construct a mathematical model of within-host influenza viral dynamics including three possible factors which determine the strength of the cross-reactive cellular adaptive immune response: the initial naive T cell number, the avidity of the interaction between T cells and the epitopes presented by infected cells, and the epitope abundance per infected cell.

CONSISE statement on the reporting of Seroepidemiologic Studies for influenza (ROSES-I statement): an extension of the STROBE statement.

Background: Population-based serologic studies are a vital tool for understanding the epidemiology of influenza and other respiratory viruses, including the early assessment of the transmissibility and severity of the 2009 influenza pandemic, and Middle East respiratory syndrome coronavirus. However, interpretation of the results of serologic studies has been hampered by the diversity of approaches and the lack of standardized methods and reporting.

Objective: The objective of the CONSISE ROSES-I statement was to improve the quality and transparency of reporting of influenza seroepidemiologic studies and facilitate the assessment of the validity and generalizability of published results.

Neutralizing inhibitors in the airways of naïve ferrets do not play a major role in modulating the virulence of H3 subtype influenza A viruses.

Many insights regarding the pathogenesis of human influenza A virus (IAV) infections have come from studies in mice and ferrets. Surfactant protein (SP)-D is the major neutralizing inhibitor of IAV in mouse airway fluids and SP-D-resistant IAV mutants show enhanced virus replication and virulence in mice. Herein, we demonstrate that sialylated glycoproteins, rather than SP-D, represent the major neutralizing inhibitors against H3 subtype viruses in airway fluids from naïve ferrets.

Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine.

Unlabelled: This study seeks to assess the ability of seasonal trivalent inactivated influenza vaccine (TIV) to induce nonneutralizing antibodies (Abs) with Fc-mediated functions in HIV-uninfected and HIV-infected subjects. Functional influenza-specific Ab responses were studied in 30 HIV-negative and 27 HIV-positive subjects immunized against seasonal influenza. All 57 subjects received the 2015 TIV.

Characterization of the Localized Immune Response in the Respiratory Tract of Ferrets following Infection with Influenza A and B Viruses.

Unlabelled: The burden of infection with seasonal influenza viruses is significant. Each year is typically characterized by the dominance of one (sub)type or lineage of influenza A or B virus, respectively. The incidence of disease varies annually, and while this may be attributed to a particular virus strain or subtype, the impacts of prior immunity, population differences, and variations in clinical assessment are also important.

Structural and functional characterisation of ferret interleukin-2.

While the ferret is a valuable animal model for a number of human viral infections, such as influenza, Hendra and Nipah, evaluating the cellular immune response following infection has been hampered by the lack of a number of species-specific immunological reagents. Interleukin 2 (IL-2) is one such key cytokine. Ferret recombinant IL-2 incorporating a C-terminal histidine tag was expressed and purified and the three-dimensional structure solved and refined at 1.

Innate Immunity and the Inter-exposure Interval Determine the Dynamics of Secondary Influenza Virus Infection and Explain Observed Viral Hierarchies.

Influenza is an infectious disease that primarily attacks the respiratory system. Innate immunity provides both a very early defense to influenza virus invasion and an effective control of viral growth. Previous modelling studies of virus-innate immune response interactions have focused on infection with a single virus and, while improving our understanding of viral and immune dynamics, have been unable to effectively evaluate the relative feasibility of different hypothesised mechanisms of antiviral immunity.

International Laboratory Comparison of Influenza Microneutralization Assays for A(H1N1)pdm09, A(H3N2), and A(H5N1) Influenza Viruses by CONSISE.

The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear.

Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model.

Background: Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference.