scholarly journals A single dose vaccination with an elastase-dependent H1N1 live attenuated swine influenza virus protects pigs from challenge with 2009 pandemic H1N1 virus

2014 ◽  
Vol 64 (1) ◽  
pp. 10-23
Author(s):  
Aleksandar Mašić ◽  
Niziti Woldeab ◽  
Carissa Embury-Hyatt ◽  
Yan Zhou ◽  
Shawn Babiuk
Keyword(s):  
Influenza Virus ◽  
Single Dose ◽  
Influenza A Virus ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Virus Infections ◽  
Intranasal Route

Abstract The 2009 outbreak of H1N1 influenza A viruses in humans underscored the importance of pigs in influenza A virus evolution and the emergence of novel viruses with pandemic potential. In addition, influenza A virus infections continued to cause production losses in the agricultural industry resulting in a significant drop of profit. The primary method to control influenza A virus infections in pigs is through vaccination. Previously we demonstrated that two doses of an elastase-dependent live attenuated swine influenza virus administered by either the intratracheal or intranasal route can provide a high degree of protection in pigs against challenge with both homologous and different heterologous swine influenza viruses. Here we report the protection efficacy of a single dose elastase-dependent live attenuated swine influenza virus administered by the intranasal route against challenge with homologous subtypic H1N1 2009 pandemic swine-like influenza virus. Protection was observed in the absence of neutralizing antibodies specific for H1N1 2009 in sera.

scholarly journals NEUTRALIZING ANTIBODIES IN HUMAN SERUM AFTER INFLUENZA A

1941 ◽  
Vol 74 (5) ◽  
pp. 433-439 ◽  
Author(s):  
F. L. Horsfall ◽  
E. R. Rickard
Keyword(s):  
Influenza Virus ◽  
Human Serum ◽  
Influenza A Virus ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Different Strains ◽  
Antibody Levels

The increased concentrations of neutralizing antibodies against influenza A virus in human serum which occur after influenza A do not differentiate between antigenically different strains of this virus or swine influenza virus but instead appear to possess equal reactivity against these agents. The decrease in antibody levels which occurs with time is also independent of the strain of virus used to measure it.

scholarly journals Immunization of Pigs with a Particle-Mediated DNA Vaccine to Influenza A Virus Protects against Challenge with Homologous Virus

1998 ◽  
Vol 72 (2) ◽  
pp. 1491-1496 ◽  
Author(s):  
Michael D. Macklin ◽  
Dennis McCabe ◽  
Martha W. McGregor ◽  
Veronica Neumann ◽  
Todd Meyer ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Influenza A Virus ◽  
Dna Vaccine ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Humoral Response ◽  
Preclinical Model ◽  
Homologous Virus

ABSTRACT Particle-mediated delivery of a DNA expression vector encoding the hemagglutinin (HA) of an H1N1 influenza virus (A/Swine/Indiana/1726/88) to porcine epidermis elicits a humoral immune response and accelerates the clearance of virus in pigs following a homotypic challenge. Mucosal administration of the HA expression plasmid elicits an immune response that is qualitatively different than that elicited by the epidermal vaccination in terms of inhibition of the initial virus infection. In contrast, delivery of a plasmid encoding an influenza virus nucleoprotein from A/PR/8/34 (H1N1) to the epidermis elicits a strong humoral response but no detectable protection in terms of nasal virus shed. The efficacy of the HA DNA vaccine was compared with that of a commercially available inactivated whole-virus vaccine as well as with the level of immunity afforded by previous infection. The HA DNA and inactivated viral vaccines elicited similar protection in that initial infection was not prevented, but subsequent amplification of the infection is limited, resulting in early clearance of the virus. Convalescent animals which recovered from exposure to virulent swine influenza virus were completely resistant to infection when challenged. The porcine influenza A virus system is a relevant preclinical model for humans in terms of both disease and gene transfer to the epidermis and thus provides a basis for advancing the development of DNA-based vaccines.

scholarly journals Resurrected ancestral influenza A viruses recapitulate the avian-to-mammalian adaptation of European avian-like swine influenza virus

2021 ◽  
Author(s):  
Wen Su ◽  
Rhodri Harfoot ◽  
Yvonne Su ◽  
Jennifer DeBeauchamp ◽  
Udayan Joseph ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Polymerase Activity ◽  
Influenza Viruses ◽  
Mammalian Host ◽  
Influenza A Viruses ◽  
Sequence Reconstruction

Abstract The emergence of a pandemic influenza virus may be better anticipated if we better understand the evolutionary steps taken by avian influenza viruses as they adapt to mammals. We used ancestral sequence reconstruction to resurrect viruses representing initial adaptive stages of the European avian-like H1N1 virus as it transitioned from avian to swine hosts. We demonstrate that efficient transmissibility in pigs was gained through stepwise adaptation after 1983. These time-dependent adaptations resulted in changes in hemagglutinin receptor binding specificity and increased viral polymerase activity. An NP-R351K mutation under strong positive selection increased the transmissibility of a reconstructed virus. The stepwise-adaptation of a wholly avian influenza virus to a mammalian host suggests a window where targeted intervention may have highest impact. Successful intervention will, however, require strategic coordination of surveillance and risk assessment activities to identify these adapting viruses and guide pandemic preparedness resources.

scholarly journals Influenza A Virus Field Surveillance at a Swine-Human Interface

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Benjamin L. Rambo-Martin ◽  
Matthew W. Keller ◽  
Malania M. Wilson ◽  
Jacqueline M. Nolting ◽  
Tavis K. Anderson ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Real Time ◽  
Influenza A Virus ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Nanopore Sequencing ◽  
Pandemic Preparedness ◽  
Human Interface ◽  
Analysis Platform

ABSTRACT While working overnight at a swine exhibition, we identified an influenza A virus (IAV) outbreak in swine, Nanopore sequenced 13 IAV genomes from samples we collected, and predicted in real time that these viruses posed a novel risk to humans due to genetic mismatches between the viruses and current prepandemic candidate vaccine viruses (CVVs). We developed and used a portable IAV sequencing and analysis platform called Mia (Mobile Influenza Analysis) to complete and characterize full-length consensus genomes approximately 18 h after unpacking the mobile lab. Exhibition swine are a known source for zoonotic transmission of IAV to humans and pose a potential pandemic risk. Genomic analyses of IAV in swine are critical to understanding this risk, the types of viruses circulating in swine, and whether current vaccines developed for use in humans would be predicted to provide immune protection. Nanopore sequencing technology has enabled genome sequencing in the field at the source of viral outbreaks or at the bedside or pen-side of infected humans and animals. The acquired data, however, have not yet demonstrated real-time, actionable public health responses. The Mia system rapidly identified three genetically distinct swine IAV lineages from three subtypes, A(H1N1), A(H3N2), and A(H1N2). Analysis of the hemagglutinin (HA) sequences of the A(H1N2) viruses identified >30 amino acid differences between the HA1 of these viruses and the most closely related CVV. As an exercise in pandemic preparedness, all sequences were emailed to CDC collaborators who initiated the development of a synthetically derived CVV. IMPORTANCE Swine are influenza virus reservoirs that have caused outbreaks and pandemics. Genomic characterization of these viruses enables pandemic risk assessment and vaccine comparisons, though this typically occurs after a novel swine virus jumps into humans. The greatest risk occurs where large groups of swine and humans comingle. At a large swine exhibition, we used Nanopore sequencing and on-site analytics to interpret 13 swine influenza virus genomes and identified an influenza virus cluster that was genetically highly varied to currently available vaccines. As part of the National Strategy for Pandemic Preparedness exercises, the sequences were emailed to colleagues at the CDC who initiated the development of a synthetically derived vaccine designed to match the viruses at the exhibition. Subsequently, this virus caused 14 infections in humans and was the dominant U.S. variant virus in 2018.

scholarly journals Novel Ranking System for Identifying Efficacious Anti-Influenza Virus PB2 Inhibitors

2015 ◽  
Vol 59 (10) ◽  
pp. 6007-6016 ◽  
Author(s):  
Alice W. Tsai ◽  
Colleen F. McNeil ◽  
Joshua R. Leeman ◽  
Hamilton B. Bennett ◽  
Kwame Nti-Addae ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Therapeutic Agents ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Whole Body ◽  
Infection Model ◽  
Virus Infections

ABSTRACTThrough antigenic drift and shifts, influenza virus infections continue to be an annual cause of morbidity in healthy populations and of death among elderly and at-risk patients. The emergence of highly pathogenic avian influenza viruses such as H5N1 and H7N9 and the rapid spread of the swine-origin H1N1 influenza virus in 2009 demonstrate the continued need for effective therapeutic agents for influenza. While several neuraminidase inhibitors have been developed for the treatment of influenza virus infections, these have shown a limited window for treatment initiation, and resistant variants have been noted in the population. In addition, an older class of antiviral drugs for influenza, the adamantanes, are no longer recommended for treatment due to widespread resistance. There remains a need for new influenza therapeutic agents with improved efficacy as well as an expanded window for the initiation of treatment. Azaindole compounds targeting the influenza A virus PB2 protein and demonstrating excellentin vitroandin vivoproperties have been identified. To evaluate thein vivoefficacy of these PB2 inhibitors, we utilized a mouse influenza A virus infection model. In addition to traditional endpoints, i.e., death, morbidity, and body weight loss, we measured lung function using whole-body plethysmography, and we used these data to develop a composite efficacy score that takes compound exposure into account. This model allowed the rapid identification and ranking of molecules relative to each other and to oseltamivir. The ability to identify compounds with enhanced preclinical properties provides an opportunity to develop more-effective treatments for influenza in patients.

scholarly journals Hemagglutinin stalk domain from H5N1 strain as a potentially universal antigen.

2014 ◽  
Vol 61 (3) ◽  
Author(s):  
Karolina Uranowska ◽  
Jolanta Tyborowska ◽  
Anna Jurek ◽  
Bogusław Szewczyk ◽  
Beata Gromadzka
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Virus Antigen ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Health Concern ◽  
Stalk Domain ◽  
Major Surface

Influenza A virus infections are the major public health concern and cause significant morbidity and mortality each year worldwide. Vaccination is the main strategy of influenza epidemic prevention. However, seasonal vaccines induce strain-specific immunity and must be reformulated annually based on prediction of the strains that will circulate in the next season. Thus, it is essential to develop vaccines that would induce broad and persistent immunity to influenza viruses. Hemagglutinin is the major surface antigen of the influenza virus. Recent studies revealed the importance of HA stalk-specific antibodies in neutralization of different influenza virus strains. Therefore, it is important to design an immunogen that would focus the immune response on the HA stalk domain in order to elicit neutralizing antibodies. In the present study, we report characterization of a conserved truncated protein, potentially a universal influenza virus antigen from the H5N1 Highly Pathogenic Avian Influenza A virus strain. Our results indicate that exposure of the HA stalk domain containing conserved epitopes results in cross reactivity with different antibodies (against group 1 and 2 HAs). Additionally, we conclude that HA stalk domain contains not only conformational epitopes recognized by universal FI6 antibody, but also linear epitopes recognized by other antibodies.

scholarly journals Influenza at the animal–human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1)

2014 ◽  
Vol 19 (18) ◽  
Author(s):  
G S Freidl ◽  
A Meijer ◽  
E de Bruin ◽  
M de Nardi ◽  
O Munoz ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Human Infection ◽  
Influenza Viruses ◽  
Diagnostic Methods ◽  
World Health ◽  
Review Of The Literature

Factors that trigger human infection with animal influenza virus progressing into a pandemic are poorly understood. Within a project developing an evidence-based risk assessment framework for influenza viruses in animals, we conducted a review of the literature for evidence of human infection with animal influenza viruses by diagnostic methods used. The review covering Medline, Embase, SciSearch and CabAbstracts yielded 6,955 articles, of which we retained 89; for influenza A(H5N1) and A(H7N9), the official case counts of the World Health Organization were used. An additional 30 studies were included by scanning the reference lists. Here, we present the findings for confirmed infections with virological evidence. We found reports of 1,419 naturally infected human cases, of which 648 were associated with avian influenza virus (AIV) A(H5N1), 375 with other AIV subtypes, and 396 with swine influenza virus (SIV). Human cases naturally infected with AIV spanned haemagglutinin subtypes H5, H6, H7, H9 and H10. SIV cases were associated with endemic SIV of H1 and H3 subtype descending from North American and Eurasian SIV lineages and various reassortants thereof. Direct exposure to birds or swine was the most likely source of infection for the cases with available information on exposure.

scholarly journals CHANGING VIRAL SUSCEPTIBILITY OF A HUMAN CELL LINE IN CONTINUOUS CULTIVATION

1961 ◽  
Vol 113 (1) ◽  
pp. 95-110 ◽  
Author(s):  
Sam C. Wong ◽  
Edwin D. Kilbourne
Keyword(s):  
Influenza Virus ◽  
Cell Line ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Continuous Cultivation ◽  
Influenza Viruses ◽  
Infective Virus ◽  
Serial Transfer ◽  
Variant Cell

During its serial transfer and cultivation in this laboratory, a human conjunctival cell line (Chang) was observed to change in morphology. Concurrently no change was noted in the susceptibility of the cells to viruses capable of infecting the original cell line. However, it was noted that the derived variant cell line had acquired susceptibility to the induction of cytopathic effects and incomplete virus formation by several strains of influenza viruses. It was then discovered that swine influenza virus and the N-WS strain of influenza A virus could be serially propagated in the derived cell line with production of infective virus. The swine virus required adaptation, but the N-WS strain did not. N-WS and swine influenza viruses multiply with infective virus formation only in the variant conjunctival cell and in no other cell line. Antigenic, cytologic, and virologic evidence is presented that the influenza virus-susceptible variant cell is of human origin and is not a contaminating cell exogenously introduced. Transition of a cell line from complete insusceptibility to susceptibility to virus infection and multiplication has not been described previously.

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