Comparison of Three Serological Assays to Determine the Cross-Reactivity of Antibodies from Eight Genetically Diverse U.S. Swine Influenza Viruses

To understand the evolution of swine-origin H3N2v influenza viruses that have infected 320 humans in the USA since August 2011, we performed a phylogenetic analysis at a whole genome scale of North American swine influenza viruses (n = 200). All viral isolates evolved from the prototypical North American H3 cluster 4 (c4), with evidence for further diversification into subclusters. At least ten distinct reassorted H3N2/pandemic H1N1 (rH3N2p) genotypes were identified in swine. Genotype 1 (G1) was most frequently detected in swine and all human H3N2v viruses clustered within a single G1 clade. These data suggest that the genetic requirements for transmission to humans may be restricted to a specific subset of swine viruses. Mutations at putative antigenic sites as well as reduced serological cross-reactivity among the H3 subclusters suggest antigenic drift of these contemporary viruses.

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Efficacy of Heterologous Prime-Boost Vaccination with H3N2 Influenza Viruses in Pre-Immune Individuals: Studies in the Pig Model

Viruses ◽

10.3390/v12090968 ◽

2020 ◽

Vol 12 (9) ◽

pp. 968

Author(s):

Sharon Chepkwony ◽

Anna Parys ◽

Elien Vandoorn ◽

Koen Chiers ◽

Kristien Van Reeth

Keyword(s):

Lymph Nodes ◽

Influenza A ◽

Serum Antibody ◽

Swine Influenza ◽

Cross Reactivity ◽

Influenza Viruses ◽

Antibody Responses ◽

Pig Model ◽

Boost Vaccination ◽

H3n2 Influenza

In a previous study in influenza-naïve pigs, heterologous prime-boost vaccination with monovalent, adjuvanted whole inactivated vaccines (WIV) based on the European swine influenza A virus (SwIAV) strain, A/swine/Gent/172/2008 (G08), followed by the US SwIAV strain, A/swine/Pennsylvania/A01076777/2010 (PA10), was shown to induce broadly cross-reactive hemagglutination inhibition (HI) antibodies against 12 out of 15 antigenically distinct H3N2 influenza strains. Here, we used the pig model to examine the efficacy of that particular heterologous prime-boost vaccination regimen, in individuals with pre-existing infection-immunity. Pigs were first inoculated intranasally with the human H3N2 strain, A/Nanchang/933/1995. Seven weeks later, they were vaccinated intramuscularly with G08 followed by PA10 or vice versa. We examined serum antibody responses against the hemagglutinin and neuraminidase, and antibody-secreting cell (ASC) responses in peripheral blood, draining lymph nodes, and nasal mucosa (NMC), in ELISPOT assays. Vaccination induced up to 10-fold higher HI antibody titers than in naïve pigs, with broader cross-reactivity, and protection against challenge with an antigenically distant H3N2 strain. It also boosted ASC responses in lymph nodes and NMC. Our results show that intramuscular administration of WIV can lead to enhanced antibody responses and cross-reactivity in pre-immune subjects, and recall of ASC responses in lymph nodes and NMC.

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IMMUNOLOGICAL RELATIONSHIP BETWEEN THE SWINE AND HUMAN INFLUENZA VIRUSES IN SWINE

Journal of Experimental Medicine ◽

10.1084/jem.66.2.151 ◽

1937 ◽

Vol 66 (2) ◽

pp. 151-168 ◽

Cited By ~ 11

Author(s):

Richard E. Shope

Keyword(s):

Influenza Virus ◽

Influenza Infection ◽

Swine Influenza Virus ◽

Swine Influenza ◽

Influenza Viruses ◽

Human Influenza ◽

Human Influenza Virus ◽

Immunological Relationship ◽

Cross Immunity ◽

The Cross

Swine recovered from infection with either swine influenza or swine influenza virus alone are usually not only immune but refractory to human influenza infection. Swine recovered from infection with a mixture of human influenza virus and H. influenzae suis are usually immune to swine influenza while those recovered from infection with human influenza virus alone are usually not immune to swine influenza. The possible mechanisms involved in the cross-immunity between the influenza viruses are discussed.

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Evaluation of Influenza Virus A/H3N2 and B Vaccines on the Basis of Cross-Reactivity of Postvaccination Human Serum Antibodies against Influenza Viruses A/H3N2 and B Isolated in MDCK Cells and Embryonated Hen Eggs

Clinical and Vaccine Immunology ◽

10.1128/cvi.05726-11 ◽

2012 ◽

Vol 19 (6) ◽

pp. 897-908 ◽

Cited By ~ 22

Author(s):

Noriko Kishida ◽

Seiichiro Fujisaki ◽

Masaru Yokoyama ◽

Hironori Sato ◽

Reiko Saito ◽

...

Keyword(s):

Influenza Virus ◽

Human Serum ◽

Neutralizing Antibodies ◽

Influenza A ◽

Geometric Mean ◽

Cross Reactivity ◽

Influenza Viruses ◽

Serum Antibodies ◽

Influenza Virus A ◽

The Cross

ABSTRACTThe vaccine strains against influenza virus A/H3N2 for the 2010-2011 season and influenza virus B for the 2009-2010 and 2010-2011 seasons in Japan are a high-growth reassortant A/Victoria/210/2009 (X-187) strain and an egg-adapted B/Brisbane/60/2008 (Victoria lineage) strain, respectively. Hemagglutination inhibition (HI) tests with postinfection ferret antisera indicated that the antisera raised against the X-187 and egg-adapted B/Brisbane/60/2008 vaccine production strains poorly inhibited recent epidemic isolates of MDCK-grown A/H3N2 and B/Victoria lineage viruses, respectively. The low reactivity of the ferret antisera may be attributable to changes in the hemagglutinin (HA) protein of production strains during egg adaptation. To evaluate the efficacy of A/H3N2 and B vaccines, the cross-reactivities of postvaccination human serum antibodies against A/H3N2 and B/Victoria lineage epidemic isolates were assessed by a comparison of the geometric mean titers (GMTs) of HI and neutralization (NT) tests. Serum antibodies elicited by the X-187 vaccine had low cross-reactivity to both MDCK- and egg-grown A/H3N2 isolates by HI test and narrow cross-reactivity by NT test in all age groups. On the other hand, the GMTs to B viruses detected by HI test were below the marginal level, so the cross-reactivity was assessed by NT test. The serum neutralizing antibodies elicited by the B/Brisbane/60/2008 vaccine reacted well with egg-grown B viruses but exhibited remarkably low reactivity to MDCK-grown B viruses. The results of these human serological studies suggest that the influenza A/H3N2 vaccine for the 2010-2011 season and B vaccine for the 2009-2010 and 2010-2011 seasons may possess insufficient efficacy and low efficacy, respectively.

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Lower seroreactivity to European than to North American H3N2 swine influenza viruses in humans, Luxembourg, 2010

Eurosurveillance ◽

10.2807/1560-7917.es2015.20.13.21078 ◽

2015 ◽

Vol 20 (13) ◽

Cited By ~ 4

Author(s):

Y Qiu ◽

C P Muller ◽

K Van Reeth

Keyword(s):

Human Serum ◽

North American ◽

Strong Correlation ◽

Haemagglutination Inhibition ◽

Swine Influenza ◽

Cross Reactivity ◽

Influenza Viruses ◽

Serum Samples ◽

Human Serum Samples ◽

The North

Seroreactivity to H3N2 swine influenza viruses (SIVs) was evaluated in serum samples collected from 843 people aged 0 to 100 years in 2010 in Luxembourg. Sera were analysed by haemagglutination inhibition (HI) and virus neutralisation (VN) assays targeting a European H3N2 SIV, a North American H3N2 variant of swine origin (H3N2v) and human seasonal H3N2 viruses isolated in 1975, 1995 and 2005. HI antibodies (titre?≥?10) against European H3N2 SIV were almost exclusively detected in those born before 1990, of whom 70% were seropositive. HI antibodies against H3N2v were predominantly found in those born before 2000, with 86% seropositive. Titres against the North American H3N2v were higher than against the European H3N2 SIV. VN patterns were similar, but with higher rates and titres. We also demonstrated lower seroreactivity to European H3N2 SIV than to North American H3N2v virus. Finally, we found a strong correlation between HI titres against the European H3N2 SIV and H3N2v and their respective human ancestors, A/Victoria/3/75 and A/Nanchang/933/95. This finding and the minimal contacts between humans and pigs in Luxembourg suggest that anti-SIV antibodies in human serum samples reflect serological cross-reactivity with historical human H3N2 viruses. Our findings help assess the pandemic risk of H3N2 SIV.

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Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1921186117 ◽

2020 ◽

Vol 117 (29) ◽

pp. 17204-17210 ◽

Cited By ~ 30

Author(s):

Honglei Sun ◽

Yihong Xiao ◽

Jiyu Liu ◽

Dayan Wang ◽

Fangtao Li ◽

...

Keyword(s):

Influenza Virus ◽

H1n1 Virus ◽

Swine Influenza Virus ◽

Swine Influenza ◽

Airway Epithelial Cells ◽

Cross Reactivity ◽

Human Infection ◽

Influenza Viruses ◽

Progeny Virus ◽

Genotype 4

Pigs are considered as important hosts or “mixing vessels” for the generation of pandemic influenza viruses. Systematic surveillance of influenza viruses in pigs is essential for early warning and preparedness for the next potential pandemic. Here, we report on an influenza virus surveillance of pigs from 2011 to 2018 in China, and identify a recently emerged genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bears 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes and has been predominant in swine populations since 2016. Similar to pdm/09 virus, G4 viruses bind to human-type receptors, produce much higher progeny virus in human airway epithelial cells, and show efficient infectivity and aerosol transmission in ferrets. Moreover, low antigenic cross-reactivity of human influenza vaccine strains with G4 reassortant EA H1N1 virus indicates that preexisting population immunity does not provide protection against G4 viruses. Further serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 y to 35 y old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity. Such infectivity greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses.

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A Single Amino Acid at Position 158 in Hemagglutinin Affects the Antigenic Property of Eurasian Avian-like H1N1 Swine Influenza Viruses

10.22541/au.162201750.02228441/v1 ◽

2021 ◽

Author(s):

Zeng Wang ◽

Yan Chen ◽

Huayuan Chen ◽

Fei Meng ◽

Shiyu Tao ◽

...

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Antigenic Variation ◽

Swine Influenza ◽

Antigenic Property ◽

Cross Reactivity ◽

Influenza Viruses ◽

Antigenic Drift ◽

Single Amino Acid ◽

Ha Protein

Influenza viruses have been posing a great threat to public health and animal industry. The developed vaccines have been widely used to reduce the risk of potential pandemic; however, the ongoing antigenic drift makes influenza virus escape from host immune response and hampers vaccine efficacy. Until now, the genetic basis of antigenic variation remains largely unknown. In this study, we used A/swine/Guangxi/18/2011 (GX/18) and A/swine/Guangdong/104/2013 (GD/104) as models to explore the molecular determinant for antigenic variation of Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses (SIVs), and found that the GD/104 virus exhibited 32~64-fold lower antigenic cross-reactivity with antibodies against GX/18 virus. Therefore, we generated polyclonal antibodies against GX/18 or GD/104 virus and a monoclonal antibody (mAb), named mAb102-95, targeted to the hemagglutinin (HA) protein of GX/18 virus, and found that a single amino acid substitution at position 158 in HA protein substantially altered the antigenicity of virus. The reactivity of GX/18 virus containing G158E mutation with the mAb102-95 decreased 8-fold than that of the parental strain. Contrarily, the reactivity of GD/104 virus bearing E158G mutation with the mAb102-95 increased by 32 times as compared with that of the parental virus. Structural analysis showed that the amino acid mutation from G to E was accompanied with the R group changing from -H to -(CH ) -COOH. The induced steric effect and increased hydrophilicity of HA protein surface jointly contributed to the antigenic drift of EA H1N1 SIVs. Our study provides experimental evidence that G158E mutation in HA protein affects the antigenic property of EA H1N1 SIVs, and widens our horizon on the antigenic drift of influenza virus.

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An isoform of the Ole e 7 allergen assembled by proteomics could explain the cross-reactivity with pollen and food nsLTPs

10.26226/morressier.5acc8ad2d462b8028d89a829 ◽

2018 ◽

Author(s):

Carmen Oeo

Keyword(s):

Cross Reactivity ◽

The Cross

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

Journal of Virology ◽

10.1128/jvi.02257-12 ◽

2012 ◽

Vol 87 (3) ◽

pp. 1400-1410 ◽

Cited By ~ 45

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.

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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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