scholarly journals Bat influenza vectored NS1-truncated live vaccine protects pigs against heterologous virus challenge

2020 ◽  
Author(s):  
Jinhwa Lee ◽  
Yonghai Li ◽  
Yuhao Li ◽  
A. Giselle Cino-Ozuna ◽  
Michael Duff ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Live Vaccine ◽  
H3n2 Virus ◽  
Swine Industry ◽  
Vaccine Candidates ◽  
Virus Challenge ◽  
Significant Difference

AbstractSwine influenza is an important disease for the swine industry. Currently used whole inactivated virus (WIV) vaccines can induce vaccine-associated enhanced respiratory disease (VAERD) in pigs when the vaccine strains mismatch with the infected viruses. Live attenuated influenza virus vaccine (LAIV) is effective to protect pigs against homologous and heterologous swine influenza virus infections without inducing VAERD, but has safety concerns due to potential reassortment with circulating viruses. Herein, we used a chimeric bat influenza Bat09:mH3mN2 virus, which contains both surface HA and NA gene open reading frames of the A/swine/Texas/4199-2/1998 (H3N2) and six internal genes from the novel bat H17N10 virus, to develop modified live-attenuated viruses (MLVs) as vaccine candidates which cannot reassort with canonical influenza A viruses by co-infection. Two attenuated MLV vaccine candidates including the virus that expresses a truncated NS1 (Bat09:mH3mN2-NS1-128, MLV1) or expresses both a truncated NS1 and the swine IL-18 (Bat09:mH3mN2-NS1-128-IL-18, MLV2) were generated and evaluated in pigs against a heterologous H3N2 virus using the WIV vaccineb as a control. Compared to the WIV vaccine, both MLV vaccines were able to reduce lesions and virus replication in lungs and limit nasal virus shedding without VAERD, also induced significantly higher levels of mucosal IgA response in lungs and significantly increased numbers of antigen-specific IFN-γ secreting cells against the challenge virus. However, no significant difference was observed in efficacy between the MLV1 and MLV2. These results indicate that bat influenza vectored MLV vaccines can be used as a safe live vaccine to prevent swine influenza.

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 High Risk of Influenza Virus Infection Among Swine Workers: Examining a Dynamic Cohort in China

2019 ◽  
Vol 71 (3) ◽  
pp. 622-629 ◽  
Author(s):  
Laura K Borkenhagen ◽  
Guo-Lin Wang ◽  
Ryan A Simmons ◽  
Zhen-Qiang Bi ◽  
Bing Lu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
High Risk ◽  
Virus Infection ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Influenza Virus Infection ◽  
Swine Influenza ◽  
Influenza A Viruses ◽  
Increased Risk ◽  
Swine Workers

Abstract Background China is thought to be a hotspot for zoonotic influenza virus emergence, yet there have been few prospective studies examining the occupational risks of such infections. Methods We present the first 2 years of data collected from a 5-year, prospective, cohort study of swine-exposed and -unexposed participants at 6 swine farms in China. We conducted serological and virological surveillance to examine evidence for swine influenza A virus infection in humans. Results Of the 658 participants (521 swine-exposed and 137 swine-unexposed), 207 (31.5%) seroconverted against at least 1 swine influenza virus subtype (swine H1N1 or H3N2). Swine-exposed participants’ microneutralization titers, especially those enrolled at confined animal feeding operations (CAFOs), were higher against the swine H1N1 virus than were other participants at 12 and 24 months. Despite elevated titers, among the 187 study subjects for whom we had complete follow-up, participants working at swine CAFOs had significantly greater odds of seroconverting against both the swine H1N1 (odds ratio [OR] 19.16, 95% confidence interval [CI] 3.55–358.65) and swine H3N2 (OR 2.97, 95% CI 1.16–8.01) viruses, compared to unexposed and non-CAFO swine workers with less intense swine exposure. Conclusions While some of the observed increased risk against swine viruses may have been explained by exposure to human influenza strains, study data suggest that even with elevated preexisting antibodies, swine-exposed workers were at high risk of infection with enzootic swine influenza A viruses.

scholarly journals Vaccines That Reduce Viral Shedding Do Not Prevent Transmission of H1N1 Pandemic 2009 Swine Influenza a Virus Infection to Unvaccinated Pigs

2020 ◽  
Author(s):  
Helen E. Everett ◽  
Pauline M. van Diemen ◽  
Mario Aramouni ◽  
Andrew Ramsay ◽  
Vivien J. Coward ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Vaccine Coverage ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Inhibitory Antibody ◽  
Virus Shedding ◽  
Virus Challenge ◽  
Viral Shedding ◽  
Swine Influenza A Virus

Swine influenza A virus (swIAV) infection causes substantial economic loss and disease burden in humans and animals. The 2009 pandemic H1N1 (pH1N1) influenza A virus is now endemic in both populations. In this study we evaluated the efficacy of different vaccines in reducing nasal shedding in pigs following pH1N1 virus challenge. We also assessed transmission from immunized and challenged to naive, directly in-contact pigs. Pigs were immunised with either adjuvanted, whole inactivated virus (WIV) vaccines or viral vectored (ChAdOx1 and MVA) vaccines expressing either the homologous or heterologous influenza A virus hemagglutinin (HA) glycoprotein as well as an influenza viral pseudotype (S-FLU) vaccine expressing heterologous HA. Only two vaccines containing homologous HA, which also induced high hemagglutination inhibitory antibody titers, significantly reduced virus shedding in challenged animals. Nevertheless, virus transmission from challenged to naive, in-contact animals occurred in all groups, although was delayed in groups of vaccinated animals with reduced virus shedding. IMPORTANCE This study was designed to determine whether vaccination of pigs with conventional, WIV or viral-vectored vaccines reduces pH1N1 swine influenza virus shedding following challenge and can prevent transmission to naive in-contact animals. Even when viral shedding was significantly reduced following challenge, infection was transmissible to susceptible co-housed recipients. This knowledge is important to inform disease surveillance and control strategies, and to determine the vaccine coverage required in a population, thereby defining disease moderation or herd protection. WIV or viral-vectored vaccines homologous to the challenge strain significantly reduced virus shedding from directly infected pigs, but vaccination did not completely prevent transmission to co-housed naive pigs.

scholarly journals Migration of the Swine Influenza Virus δ-Cluster Hemagglutinin N-Linked Glycosylation Site from N142 to N144 Results in Loss of Antibody Cross-Reactivity

2012 ◽  
Vol 19 (9) ◽  
pp. 1457-1464 ◽  
Author(s):  
Ben M. Hause ◽  
Douglas L. Stine ◽  
Zizhang Sheng ◽  
Zhao Wang ◽  
Suvobrata Chakravarty ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Consensus Sequence ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Cross Reactivity ◽  
Glycosylation Site ◽  
Sequencing Analysis ◽  
Serum Neutralization ◽  
Glycosylation Sites

ABSTRACTRoutine antigenic characterization of swine influenza virus isolates in a high-throughput serum neutralization (HTSN) assay found that approximately 20% of isolates were not neutralized by a panel of reference antisera. Genetic analysis revealed that nearly all of the neutralization-resistant isolates possessed a seasonal human-lineage hemagglutinin (HA; δ cluster). Subsequent sequencing analysis of full-length HA identified a conserved N144 residue present only in neutralization-resistant strains. N144 lies in a predicted N-linked glycosylation consensus sequence, i.e., N-X-S/T (where X is any amino acid except for proline). Interestingly, neutralization-sensitive viruses all had predicted N-linked glycosylation sites at N137 or N142, with threonine (T) occupying position 144 of HA. Consistent with the HTSN assay, hemagglutination inhibition (HI) and serum neutralization (SN) assays demonstrated that migration of the potential N-linked glycosylation site from N137 or N142 to N144 resulted in a >8-fold decrease in titers. These results were further confirmed in a reverse genetics system where syngeneic viruses varying only by predicted N-glycosylation sites at either N142 or N144 exhibited distinct antigenic characteristics like those observed in field isolates. Molecular modeling of the hemagglutinin protein containing N142 or N144 in complex with a neutralizing antibody suggested that N144-induced potential glycosylation may sterically hinder access of antibodies to the hemagglutinin head domain, allowing viruses to escape neutralization. Since N-linked glycosylation at these sites has been implicated in genetic and antigenic evolution of human influenza A viruses, we conclude that the relocation of the hemagglutinin N-linked glycosylation site from N142 to N144 renders swine influenza virus δ-cluster viruses resistant to antibody-mediated neutralization.

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 Pathogenesis of Pandemic Influenza A (H1N1) and Triple-Reassortant Swine Influenza A (H1) Viruses in Mice

2010 ◽  
Vol 84 (9) ◽  
pp. 4194-4203 ◽  
Author(s):  
Jessica A. Belser ◽  
Debra A. Wadford ◽  
Claudia Pappas ◽  
Kortney M. Gustin ◽  
Taronna R. Maines ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
H1n1 Virus ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
The United States ◽  
Chemokine Production ◽  
Highly Pathogenic ◽  
Influenza A H1n1 ◽  
2009 H1n1

ABSTRACT The pandemic H1N1 virus of 2009 (2009 H1N1) continues to cause illness worldwide, primarily in younger age groups. To better understand the pathogenesis of these viruses in mammals, we used a mouse model to evaluate the relative virulence of selected 2009 H1N1 viruses and compared them to a representative human triple-reassortant swine influenza virus that has circulated in pigs in the United States for over a decade preceding the current pandemic. Additional comparisons were made with the reconstructed 1918 virus, a 1976 H1N1 swine influenza virus, and a highly pathogenic H5N1 virus. Mice were inoculated intranasally with each virus and monitored for morbidity, mortality, viral replication, hemostatic parameters, cytokine production, and lung histology. All 2009 H1N1 viruses replicated efficiently in the lungs of mice and possessed a high degree of infectivity but did not cause lethal disease or exhibit extrapulmonary virus spread. Transient weight loss, lymphopenia, and proinflammatory cytokine and chemokine production were present following 2009 H1N1 virus infection, but these levels were generally muted compared with a triple-reassortant swine virus and the 1918 virus. 2009 H1N1 viruses isolated from fatal cases did not demonstrate enhanced virulence in this model compared with isolates from mild human cases. Histologically, infection with the 2009 viruses resulted in lesions in the lung varying from mild to moderate bronchiolitis with occasional necrosis of bronchiolar epithelium and mild to moderate peribronchiolar alveolitis. Taken together, these studies demonstrate that the 2009 H1N1 viruses exhibited mild to moderate virulence in mice compared with highly pathogenic viruses.

scholarly journals Isolation of H3N2 Swine Influenza Virus in South Korea

2003 ◽  
Vol 15 (1) ◽  
pp. 30-34 ◽  
Author(s):  
Dae S. Song ◽  
Jae Y. Lee ◽  
Jin S. Oh ◽  
Kwang S. Lyoo ◽  
Kyung J. Yoon ◽  
...  
Keyword(s):  
Influenza Virus ◽  
South Korea ◽  
Respiratory Disease ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
H3n2 Virus ◽  
Pcr Products ◽  
Swine Population ◽  
Swine Herds

Swine influenza is a significant respiratory disease causing occasional reproductive problems in nïve swine herds. Although different subtypes of swine influenza virus (SIV) have been implicated in clinical outbreaks of swine influenza in Asian countries, no virus isolation has been made to identify SIV of subtypes other than the H1N1 subtype in the Korean swine population. In December 1998, an outbreak of acute respiratory disease was identified in a commercial swine farm located in the Kyunggi province of South Korea. A causative agent, which agglutinated rooster red blood cells, was detected from the lungs of 3 piglets from the index herd and was determined to be type A influenza virus using a commercial influenza virus typing kit. Hemagglutination activity (HA) of the isolates was completely inhibited by a swine antiserum against a recent US H3N2 SIV isolate (A/Sw/IA/41305/1998) but not by H1N1 swine antiserum (A/Sw/IA/1979). Reverse transcription–polymerase chain reaction (RT-PCR) revealed all 3 isolates were H3 SIV subtypes. Sequence analysis of hemagglutinin gene PCR products supported the belief that the Korean H3 SIV isolates were genetically similar to the known mammalian H3 influenza viruses. This is the first report on a clinical outbreak of swine influenza caused by the H3N2 virus in Korea.

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 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.

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