Comparable Fitness and Transmissibility between Oseltamivir-Resistant Pandemic 2009 and Seasonal H1N1 Influenza Viruses with the H275Y Neuraminidase Mutation

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.

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

Vaccines ◽

10.3390/vaccines9070793 ◽

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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Origin of the European avian-like swine influenza viruses

Journal of General Virology ◽

10.1099/vir.0.068569-0 ◽

2014 ◽

Vol 95 (11) ◽

pp. 2372-2376 ◽

Cited By ~ 10

Author(s):

Andi Krumbholz ◽

Jeannette Lange ◽

Andreas Sauerbrei ◽

Marco Groth ◽

Matthias Platzer ◽

...

Keyword(s):

Avian Influenza ◽

Phylogenetic Trees ◽

Sequence Data ◽

Swine Influenza ◽

H1n1 Influenza ◽

Molecular Data ◽

Influenza Viruses ◽

Time Resolved ◽

Genotype Constellation ◽

Tree Inference

The avian-like swine influenza viruses emerged in 1979 in Belgium and Germany. Thereafter, they spread through many European swine-producing countries, replaced the circulating classical swine H1N1 influenza viruses, and became endemic. Serological and subsequent molecular data indicated an avian source, but details remained obscure due to a lack of relevant avian influenza virus sequence data. Here, the origin of the European avian-like swine influenza viruses was analysed using a collection of 16 European swine H1N1 influenza viruses sampled in 1979–1981 in Germany, the Netherlands, Belgium, Italy and France, as well as several contemporaneous avian influenza viruses of various serotypes. The phylogenetic trees suggested a triple reassortant with a unique genotype constellation. Time-resolved maximum clade credibility trees indicated times to the most recent common ancestors of 34–46 years (before 2008) depending on the RNA segment and the method of tree inference.

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In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses

Nature ◽

10.1038/nature08260 ◽

2009 ◽

Vol 460 (7258) ◽

pp. 1021-1025 ◽

Cited By ~ 763

Author(s):

Yasushi Itoh ◽

Kyoko Shinya ◽

Maki Kiso ◽

Tokiko Watanabe ◽

Yoshihiro Sakoda ◽

...

Keyword(s):

H1n1 Influenza ◽

Influenza Viruses ◽

In Vivo Characterization

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Comparison Of Host Responses Elicited By Avian H5N1, 2009 Pandemic H1N1, And Seasonal H1N1 Influenza Viruses In Human Airway Epithelial Cells

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a6022 ◽

2011 ◽

Author(s):

Anand C. Patel ◽

Noah Yoo ◽

Subhajit Poddar ◽

Nadezhda E. Yun ◽

Yong Zhang ◽

...

Keyword(s):

Epithelial Cells ◽

H1n1 Influenza ◽

Airway Epithelial Cells ◽

Influenza Viruses ◽

Host Responses ◽

Pandemic H1n1 ◽

Airway Epithelial ◽

Human Airway ◽

Human Airway Epithelial Cells

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Historical H1N1 Influenza Virus Imprinting Increases Vaccine Protection by Influencing the Activity and Sustained Production of Antibodies Elicited at Vaccination in Ferrets

Vaccines ◽

10.3390/vaccines7040133 ◽

2019 ◽

Vol 7 (4) ◽

pp. 133 ◽

Cited By ~ 7

Author(s):

Magen E. Francis ◽

Mara McNeil ◽

Nicholas J. Dawe ◽

Mary K. Foley ◽

Morgan L. King ◽

...

Keyword(s):

Influenza Virus ◽

Immune Responses ◽

Time Course ◽

Recovery Period ◽

Haemagglutination Inhibition ◽

H1n1 Influenza ◽

Influenza Viruses ◽

Immune Memory ◽

Sublethal Dose ◽

Virus Infections

Influenza virus imprinting is now understood to significantly influence the immune responses and clinical outcome of influenza virus infections that occur later in life. Due to the yearly cycling of influenza viruses, humans are imprinted with the circulating virus of their birth year and subsequently build a complex influenza virus immune history. Despite this knowledge, little is known about how the imprinting strain influences vaccine responses. To investigate the immune responses of the imprinted host to split-virion vaccination, we imprinted ferrets with a sublethal dose of the historical seasonal H1N1 strain A/USSR/90/1977. After a +60-day recovery period to build immune memory, ferrets were immunized and then challenged on Day 123. Antibody specificity and recall were investigated throughout the time course. At challenge, the imprinted vaccinated ferrets did not experience significant disease, while naïve-vaccinated ferrets had significant weight loss. Haemagglutination inhibition assays showed that imprinted ferrets had a more robust antibody response post vaccination and increased virus neutralization activity. Imprinted-vaccinated animals had increased virus-specific IgG antibodies compared to the other experimental groups, suggesting B-cell maturity and plasticity at vaccination. These results should be considered when designing the next generation of influenza vaccines.

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Antigenic drift of hemagglutinin and neuraminidase in seasonal H1N1 influenza viruses from Saudi Arabia in 2014 to 2015

Journal of Medical Virology ◽

10.1002/jmv.25759 ◽

2020 ◽

Vol 92 (12) ◽

pp. 3016-3027 ◽

Cited By ~ 1

Author(s):

Asif Naeem ◽

Karim Elbakkouri ◽

Ali Alfaiz ◽

Maaweya E. Hamed ◽

Hadel Alsaran ◽

...

Keyword(s):

Saudi Arabia ◽

H1n1 Influenza ◽

Influenza Viruses ◽

Antigenic Drift

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Evolution of 2009 H1N1 influenza viruses during the pandemic correlates with increased viral pathogenicity and transmissibility in the ferret model

Scientific Reports ◽

10.1038/srep28583 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 11

Author(s):

Anna Otte ◽

Anthony C. Marriott ◽

Carola Dreier ◽

Brian Dove ◽

Kyra Mooren ◽

...

Keyword(s):

H1n1 Influenza ◽

Influenza Viruses ◽

2009 H1n1

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New 2013 incidence peak in childhood narcolepsy: more than vaccination?

SLEEP ◽

10.1093/sleep/zsaa172 ◽

2020 ◽

Author(s):

Zhongxing Zhang ◽

Jari K Gool ◽

Rolf Fronczek ◽

Yves Dauvilliers ◽

Claudio L A Bassetti ◽

...

Keyword(s):

De Novo ◽

Influenza Pandemic ◽

Disease Onset ◽

Fold Increase ◽

H1n1 Influenza ◽

Incidence Rates ◽

Influenza Viruses ◽

Smoothing Methods ◽

Immune Mediated ◽

Data Driven Modeling

Abstract Increased incidence rates of narcolepsy type-1 (NT1) have been reported worldwide after the 2009–2010 H1N1 influenza pandemic (pH1N1). While some European countries found an association between the NT1 incidence increase and the H1N1 vaccination Pandemrix, reports from Asian countries suggested the H1N1 virus itself to be linked to the increased NT1 incidence. Using robust data-driven modeling approaches, that is, locally estimated scatterplot smoothing methods, we analyzed the number of de novo NT1 cases (n = 508) in the last two decades using the European Narcolepsy Network database. We confirmed the peak of NT1 incidence in 2010, that is, 2.54-fold (95% confidence interval [CI]: [2.11, 3.19]) increase in NT1 onset following 2009–2010 pH1N1. This peak in 2010 was found in both childhood NT1 (2.75-fold increase, 95% CI: [1.95, 4.69]) and adulthood NT1 (2.43-fold increase, 95% CI: [2.05, 2.97]). In addition, we identified a new peak in 2013 that is age-specific for children/adolescents (i.e. 2.09-fold increase, 95% CI: [1.52, 3.32]). Most of these children/adolescents were HLA DQB1*06:02 positive and showed a subacute disease onset consistent with an immune-mediated type of narcolepsy. The new 2013 incidence peak is likely not related to Pandemrix as it was not used after 2010. Our results suggest that the increased NT1 incidence after 2009–2010 pH1N1 is not unique and our study provides an opportunity to develop new hypotheses, for example, considering other (influenza) viruses or epidemiological events to further investigate the pathophysiology of immune-mediated narcolepsy.

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