scholarly journals Experimental Infection of Pigs with the Human 1918 Pandemic Influenza Virus

2009 ◽  
Vol 83 (9) ◽  
pp. 4287-4296 ◽  
Author(s):  
Hana M. Weingartl ◽  
Randy A. Albrecht ◽  
Kelly M. Lager ◽  
Shawn Babiuk ◽  
Peter Marszal ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Pandemic Influenza ◽  
H1n1 Virus ◽  
Swine Influenza ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
H1n1 Influenza Virus ◽  
Severe Respiratory Distress ◽  
Pandemic H1n1 Influenza ◽  
Spanish Flu

ABSTRACT Swine influenza was first recognized as a disease entity during the 1918 “Spanish flu” pandemic. The aim of this work was to determine the virulence of a plasmid-derived human 1918 pandemic H1N1 influenza virus (reconstructed 1918, or 1918/rec, virus) in swine using a plasmid-derived A/swine/Iowa/15/1930 H1N1 virus (1930/rec virus), representing the first isolated influenza virus, as a reference. Four-week-old piglets were inoculated intratracheally with either the 1930/rec or the 1918/rec virus or intranasally with the 1918/rec virus. A transient increase in temperature and mild respiratory signs developed postinoculation in all virus-inoculated groups. In contrast to other mammalian hosts (mice, ferrets, and macaques) where infection with the 1918/rec virus was lethal, the pigs did not develop severe respiratory distress or become moribund. Virus titers in the lower respiratory tract as well as macro- and microscopic lesions at 3 and 5 days postinfection (dpi) were comparable between the 1930/rec and 1918/rec virus-inoculated animals. In contrast to the 1930/rec virus-infected animals, at 7 dpi prominent lung lesions were present in only the 1918/rec virus-infected animals, and all the piglets developed antibodies at 7 dpi. Presented data support the hypothesis that the 1918 pandemic influenza virus was able to infect and replicate in swine, causing a respiratory disease, and that the virus was likely introduced into the pig population during the 1918 pandemic, resulting in the current lineage of the classical H1N1 swine influenza viruses.

scholarly journals Contemporary Seasonal Influenza A (H1N1) Virus Infection Primes for a More Robust Response To Split Inactivated Pandemic Influenza A (H1N1) Virus Vaccination in Ferrets

2010 ◽  
Vol 17 (12) ◽  
pp. 1998-2006 ◽  
Author(s):  
Ali H. Ellebedy ◽  
Thomas P. Fabrizio ◽  
Ghazi Kayali ◽  
Thomas H. Oguin ◽  
Scott A. Brown ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Seasonal Influenza ◽  
H1n1 Virus ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Inactivated Vaccine ◽  
H1n1 Influenza Virus ◽  
Influenza A H1n1

ABSTRACT Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8+ cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans.

Recombinant H1N1 virus-like particle vaccine elicits protective immunity in ferrets against the 2009 pandemic H1N1 influenza virus

Vaccine ◽  
2010 ◽  
Vol 28 (30) ◽  
pp. 4771-4776 ◽  
Author(s):  
Peter Pushko ◽  
Thomas Kort ◽  
Margret Nathan ◽  
Melissa B. Pearce ◽  
Gale Smith ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Protective Immunity ◽  
H1n1 Virus ◽  
H1n1 Influenza ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus ◽  
Pandemic H1n1 Influenza ◽  
Virus Like Particle

Emergence and characterisation of pandemic H1N1 influenza viruses in Hungarian swine herds

2013 ◽  
Vol 61 (1) ◽  
pp. 125-134 ◽  
Author(s):  
Ádám Bálint ◽  
István Kiss ◽  
Krisztián Bányai ◽  
Imre Biksi ◽  
Katalin Szentpáli-Gavallér ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Viral Fitness ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus ◽  
Pandemic H1n1 Influenza ◽  
Molecular Features ◽  
Swine Herds

In 2010, two novel porcine H1N1 influenza viruses were isolated from pigs with influenza-like illness in Hungarian swine herds. Sequence and phylogenetic analysis of these strains revealed that they shared molecular features with the pandemic H1N1 influenza virus strains, which emerged globally during 2009. The PB2, HA and NA genes contained unique amino acid changes compared to the available new H1N1 influenza virus sequences of pig origin. Furthermore, the investigated strains could be separated with respect to parallel amino acid substitutions affecting the polymerase genes (PB2, PB1 and PA) and the nucleoprotein (NP) gene, supporting the proposed complementarities between these proteins, all required for the viral fitness. Molecular characterisation of two Hungarian human pandemic H1N1 isolates was also performed, so that we could compare contemporaneous strains of different host species origins. Shared molecular motifs in various genes of animal and human influenza strains suggested that the Hungarian porcine strains could have originated from humans through direct interspecies transmission. This study is among the few that support the natural human-to-pig transmission of the pandemic H1N1 influenza virus.

scholarly journals Swine Influenza H1N1 Virus Induces Acute Inflammatory Immune Responses in Pig Lungs: a Potential Animal Model for Human H1N1 Influenza Virus

2010 ◽  
Vol 84 (21) ◽  
pp. 11210-11218 ◽  
Author(s):  
Mahesh Khatri ◽  
Varun Dwivedi ◽  
Steven Krakowka ◽  
Cordelia Manickam ◽  
Ahmed Ali ◽  
...  
Keyword(s):  
Animal Model ◽  
T Cells ◽  
Influenza Virus ◽  
Immune Responses ◽  
Swine Influenza ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Nasal Discharge ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus

ABSTRACT Pigs are capable of generating reassortant influenza viruses of pandemic potential, as both the avian and mammalian influenza viruses can infect pig epithelial cells in the respiratory tract. The source of the current influenza pandemic is H1N1 influenza A virus, possibly of swine origin. This study was conducted to understand better the pathogenesis of H1N1 influenza virus and associated host mucosal immune responses during acute infection in humans. Therefore, we chose a H1N1 swine influenza virus, Sw/OH/24366/07 (SwIV), which has a history of transmission to humans. Clinically, inoculated pigs had nasal discharge and fever and shed virus through nasal secretions. Like pandemic H1N1, SwIV also replicated extensively in both the upper and lower respiratory tracts, and lung lesions were typical of H1N1 infection. We detected innate, proinflammatory, Th1, Th2, and Th3 cytokines, as well as SwIV-specific IgA antibody in lungs of the virus-inoculated pigs. Production of IFN-γ by lymphocytes of the tracheobronchial lymph nodes was also detected. Higher frequencies of cytotoxic T lymphocytes, γδ T cells, dendritic cells, activated T cells, and CD4+ and CD8+ T cells were detected in SwIV-infected pig lungs. Concomitantly, higher frequencies of the immunosuppressive T regulatory cells were also detected in the virus-infected pig lungs. The findings of this study have relevance to pathogenesis of the pandemic H1N1 influenza virus in humans; thus, pigs may serve as a useful animal model to design and test effective mucosal vaccines and therapeutics against influenza virus.

Reassortment ability of the 2009 pandemic H1N1 influenza virus with circulating human and avian influenza viruses: Public health risk implications

2013 ◽  
Vol 175 (2) ◽  
pp. 151-154 ◽  
Author(s):  
Maria Stincarelli ◽  
Rosaria Arvia ◽  
Maria Alessandra De Marco ◽  
Valeria Clausi ◽  
Fabiana Corcioli ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza Virus ◽  
Avian Influenza ◽  
Health Risk ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus ◽  
Avian Influenza Viruses ◽  
Pandemic H1n1 Influenza

scholarly journals DNA Vaccination Elicits Protective Immune Responses against Pandemic and Classic Swine Influenza Viruses in Pigs

2011 ◽  
Vol 18 (11) ◽  
pp. 1987-1995 ◽  
Author(s):  
J. Patrick Gorres ◽  
Kelly M. Lager ◽  
Wing-Pui Kong ◽  
Michael Royals ◽  
John-Paul Todd ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza Virus ◽  
Swine Influenza ◽  
H1n1 Influenza ◽  
Dna Vaccination ◽  
Influenza Viruses ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus ◽  
Promising Alternative ◽  
Pork Industry

ABSTRACTSwine influenza is a highly contagious viral infection in pigs that significantly impacts the pork industry due to weight loss and secondary infections. There is also the potential of a significant threat to public health, as was seen in 2009 when the pandemic H1N1 influenza virus strain emerged from reassortment events among avian, swine, and human influenza viruses within pigs. As classic and pandemic H1N1 strains now circulate in swine, an effective vaccine may be the best strategy to protect the pork industry and public health. Current inactivated-virus vaccines available for swine influenza protect only against viral strains closely related to the vaccine strain, and egg-based production of these vaccines is insufficient to respond to large outbreaks. DNA vaccines are a promising alternative since they can potentially induce broad-based protection with more efficient production methods. In this study we evaluated the potentials of monovalent and trivalent DNA vaccine constructs to (i) elicit both humoral and gamma interferon (IFN-γ) responses and (ii) protect pigs against viral shedding and lung disease after challenge with pandemic H1N1 or classic swine H1N1 influenza virus. We also compared the efficiency of a needle-free vaccine delivery method to that of a conventional needle/syringe injection. We report that DNA vaccination elicits robust serum antibody and cellular responses after three immunizations and confers significant protection against influenza virus challenge. Needle-free delivery elicited improved antibody responses with the same efficiency as conventional injection and should be considered for development as a practical alternative for vaccine administration.

scholarly journals Sequential Seasonal H1N1 Influenza Virus Infections Protect Ferrets against Novel 2009 H1N1 Influenza Virus

2012 ◽  
Vol 87 (3) ◽  
pp. 1400-1410 ◽  
Author(s):  
Donald M. Carter ◽  
Chalise E. Bloom ◽  
Eduardo J. M. Nascimento ◽  
Ernesto T. A. Marques ◽  
Jodi K. Craigo ◽  
...  
Keyword(s):  
Influenza Virus ◽  
H1n1 Influenza ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
The Novel ◽  
Virus Infections ◽  
H1n1 Influenza Virus ◽  
Virus Shedding ◽  
2009 H1n1 ◽  
Novel H1n1 Influenza

ABSTRACTIndividuals <60 years of age had the lowest incidence of infection, with ∼25% of these people having preexisting, cross-reactive antibodies to novel 2009 H1N1 influenza. Many people >60 years old also had preexisting antibodies to novel H1N1. These observations are puzzling because the seasonal H1N1 viruses circulating during the last 60 years were not antigenically similar to novel H1N1. We therefore hypothesized that a sequence of exposures to antigenically different seasonal H1N1 viruses can elicit an antibody response that protects against novel 2009 H1N1. Ferrets were preinfected with seasonal H1N1 viruses and assessed for cross-reactive antibodies to novel H1N1. Serum from infected ferrets was assayed for cross-reactivity to both seasonal and novel 2009 H1N1 strains. These results were compared to those of ferrets that were sequentially infected with H1N1 viruses isolated prior to 1957 or more-recently isolated viruses. Following seroconversion, ferrets were challenged with novel H1N1 influenza virus and assessed for viral titers in the nasal wash, morbidity, and mortality. There was no hemagglutination inhibition (HAI) cross-reactivity in ferrets infected with any single seasonal H1N1 influenza viruses, with limited protection to challenge. However, sequential H1N1 influenza infections reduced the incidence of disease and elicited cross-reactive antibodies to novel H1N1 isolates. The amount and duration of virus shedding and the frequency of transmission following novel H1N1 challenge were reduced. Exposure to multiple seasonal H1N1 influenza viruses, and not to any single H1N1 influenza virus, elicits a breadth of antibodies that neutralize novel H1N1 even though the host was never exposed to the novel H1N1 influenza viruses.

scholarly journals Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 793
Author(s):  
Ying Huang ◽  
Monique S. França ◽  
James D. Allen ◽  
Hua Shi ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
H1n1 Virus ◽  
Influenza Virus Infection ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Next Generation ◽  
Wild Type ◽  
Influenza A H1n1

Vaccination is the best way to prevent influenza virus infections, but the diversity of antigenically distinct isolates is a persistent challenge for vaccine development. In order to conquer the antigenic variability and improve influenza virus vaccine efficacy, our research group has developed computationally optimized broadly reactive antigens (COBRAs) in the form of recombinant hemagglutinins (rHAs) to elicit broader immune responses. However, previous COBRA H1N1 vaccines do not elicit immune responses that neutralize H1N1 virus strains in circulation during the recent years. In order to update our COBRA vaccine, two new candidate COBRA HA vaccines, Y2 and Y4, were generated using a new seasonal-based COBRA methodology derived from H1N1 isolates that circulated during 2013–2019. In this study, the effectiveness of COBRA Y2 and Y4 vaccines were evaluated in mice, and the elicited immune responses were compared to those generated by historical H1 COBRA HA and wild-type H1N1 HA vaccines. Mice vaccinated with the next generation COBRA HA vaccines effectively protected against morbidity and mortality after infection with H1N1 influenza viruses. The antibodies elicited by the COBRA HA vaccines were highly cross-reactive with influenza A (H1N1) pdm09-like viruses isolated from 2009 to 2021, especially with the most recent circulating viruses from 2019 to 2021. Furthermore, viral loads in lungs of mice vaccinated with Y2 and Y4 were dramatically reduced to low or undetectable levels, resulting in minimal lung injury compared to wild-type HA vaccines following H1N1 influenza virus infection.

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