Multiple Infections with Seasonal Influenza A Virus Induce Cross‐Protective Immunity against A(H1N1) Pandemic Influenza Virus in a Ferret Model

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.

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Immunogenicity, Boostability, and Sustainability of the Immune Response after Vaccination against Influenza A Virus (H1N1) 2009 in a Healthy Population

Clinical and Vaccine Immunology ◽

10.1128/cvi.05046-11 ◽

2011 ◽

Vol 18 (9) ◽

pp. 1401-1405 ◽

Cited By ~ 36

Author(s):

Elisabeth Huijskens ◽

John Rossen ◽

Paul Mulder ◽

Ruud van Beek ◽

Hennie van Vugt ◽

...

Keyword(s):

Immune Response ◽

Influenza Virus ◽

Influenza A Virus ◽

Influenza A ◽

Seasonal Influenza ◽

Virus H1n1 ◽

Prospective Longitudinal Study ◽

Virus Vaccination ◽

Short Period ◽

Prospective Longitudinal

ABSTRACTThe emergence of a new influenza A virus (H1N1) variant in 2009 led to a worldwide vaccination program, which was prepared in a relatively short period of time. This study investigated the humoral immunity against this virus before and after vaccination with a 2009 influenza A virus (H1N1) monovalent MF59-adjuvanted vaccine, as well as the persistence of vaccine-induced antibodies. Our prospective longitudinal study included 498 health care workers (mean age, 43 years; median age, 44 years). Most (89%) had never or only occasionally received a seasonal influenza virus vaccine, and 11% were vaccinated annually (on average, for >10 years). Antibody titers were determined by a hemagglutination inhibition (HI) assay at baseline, 3 weeks after the first vaccination, and 5 weeks and 7 months after the second vaccination. Four hundred thirty-five persons received two doses of the 2009 vaccine. After the first dose, 79.5% developed a HI titer of ≥40. This percentage increased to 83.3% after the second dose. Persistent antibodies were found in 71.9% of the group that had not received annual vaccinations and in 43.8% of the group that had received annual vaccinations. The latter group tended to have lower HI titers (P=0.09). With increasing age, HI titers decreased significantly, by 2.4% per year. A single dose of the 2009 vaccine was immunogenic in almost 80% of the study population, whereas an additional dose resulted in significantly increased titers only in persons over 50. Finally, a reduced HI antibody response against the 2009 vaccine was found in adults who had previously received seasonal influenza virus vaccination. More studies on the effect of yearly seasonal influenza virus vaccination on the immune response are warranted.

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Intermonomer Interactions in Hemagglutinin Subunits HA1 and HA2 Affecting Hemagglutinin Stability and Influenza Virus Infectivity

Journal of Virology ◽

10.1128/jvi.00939-15 ◽

2015 ◽

Vol 89 (20) ◽

pp. 10602-10611 ◽

Cited By ~ 14

Author(s):

Wei Wang ◽

Christopher J. DeFeo ◽

Esmeralda Alvarado-Facundo ◽

Russell Vassell ◽

Carol D. Weiss

Keyword(s):

Influenza Virus ◽

Influenza A Virus ◽

Influenza A ◽

Seasonal Influenza ◽

Virus Entry ◽

H1n1 Influenza ◽

Fusion Peptide ◽

Virus Infectivity ◽

Influenza Virus Hemagglutinin ◽

2009 H1n1

ABSTRACTInfluenza virus hemagglutinin (HA) mediates virus entry by binding to cell surface receptors and fusing the viral and endosomal membranes following uptake by endocytosis. The acidic environment of endosomes triggers a large-scale conformational change in the transmembrane subunit of HA (HA2) involving a loop (B loop)-to-helix transition, which releases the fusion peptide at the HA2 N terminus from an interior pocket within the HA trimer. Subsequent insertion of the fusion peptide into the endosomal membrane initiates fusion. The acid stability of HA is influenced by residues in the fusion peptide, fusion peptide pocket, coiled-coil regions of HA2, and interactions between the surface (HA1) and HA2 subunits, but details are not fully understood and vary among strains. Current evidence suggests that the HA from the circulating pandemic 2009 H1N1 influenza A virus [A(H1N1)pdm09] is less stable than the HAs from other seasonal influenza virus strains. Here we show that residue 205 in HA1 and residue 399 in the B loop of HA2 (residue 72, HA2 numbering) in different monomers of the trimeric A(H1N1)pdm09 HA are involved in functionally important intermolecular interactions and that a conserved histidine in this pair helps regulate HA stability. An arginine-lysine pair at this location destabilizes HA at acidic pH and mediates fusion at a higher pH, while a glutamate-lysine pair enhances HA stability and requires a lower pH to induce fusion. Our findings identify key residues in HA1 and HA2 that interact to help regulate H1N1 HA stability and virus infectivity.IMPORTANCEInfluenza virus hemagglutinin (HA) is the principal antigen in inactivated influenza vaccines and the target of protective antibodies. However, the influenza A virus HA is highly variable, necessitating frequent vaccine changes to match circulating strains. Sequence changes in HA affect not only antigenicity but also HA stability, which has important implications for vaccine production, as well as viral adaptation to hosts. HA from the pandemic 2009 H1N1 influenza A virus is less stable than other recent seasonal influenza virus HAs, but the molecular interactions that contribute to HA stability are not fully understood. Here we identify molecular interactions between specific residues in the surface and transmembrane subunits of HA that help regulate the HA conformational changes needed for HA stability and virus entry. These findings contribute to our understanding of the molecular mechanisms controlling HA function and antigen stability.

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Influenza Viruses in Mice: Deep Sequencing Analysis of Serial Passage and Effects of Sialic Acid Structural Variation

Journal of Virology ◽

10.1128/jvi.01039-19 ◽

2019 ◽

Vol 93 (23) ◽

Cited By ~ 6

Author(s):

Brian R. Wasik ◽

Ian E. H. Voorhees ◽

Karen N. Barnard ◽

Brynn K. Alford-Lawrence ◽

Wendy S. Weichert ◽

...

Keyword(s):

Influenza Virus ◽

Sialic Acid ◽

Influenza A Virus ◽

Deep Sequencing ◽

Influenza A ◽

Natural Host ◽

H1n1 Pandemic ◽

Influenza A Viruses ◽

Canine Influenza Virus ◽

Canine Influenza

ABSTRACT Influenza A viruses have regularly jumped to new host species to cause epidemics or pandemics, an evolutionary process that involves variation in the viral traits necessary to overcome host barriers and facilitate transmission. Mice are not a natural host for influenza virus but are frequently used as models in studies of pathogenesis, often after multiple passages to achieve higher viral titers that result in clinical disease such as weight loss or death. Here, we examine the processes of influenza A virus infection and evolution in mice by comparing single nucleotide variations of a human H1N1 pandemic virus, a seasonal H3N2 virus, and an H3N2 canine influenza virus during experimental passage. We also compared replication and sequence variation in wild-type mice expressing N-glycolylneuraminic acid (Neu5Gc) with those seen in mice expressing only N-acetylneuraminic acid (Neu5Ac). Viruses derived from plasmids were propagated in MDCK cells and then passaged in mice up to four times. Full-genome deep sequencing of the plasmids, cultured viruses, and viruses from mice at various passages revealed only small numbers of mutational changes. The H3N2 canine influenza virus showed increases in frequency of sporadic mutations in the PB2, PA, and NA segments. The H1N1 pandemic virus grew well in mice, and while it exhibited the maintenance of some minority mutations, there was no clear evidence for adaptive evolution. The H3N2 seasonal virus did not establish in the mice. Finally, there were no clear sequence differences associated with the presence or absence of Neu5Gc. IMPORTANCE Mice are commonly used as a model to study the growth and virulence of influenza A viruses in mammals but are not a natural host and have distinct sialic acid receptor profiles compared to humans. Using experimental infections with different subtypes of influenza A virus derived from different hosts, we found that evolution of influenza A virus in mice did not necessarily proceed through the linear accumulation of host-adaptive mutations, that there was variation in the patterns of mutations detected in each repetition, and that the mutation dynamics depended on the virus examined. In addition, variation in the viral receptor, sialic acid, did not affect influenza virus evolution in this model. Overall, our results show that while mice provide a useful animal model for influenza virus pathology, host passage evolution will vary depending on the specific virus tested.

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Assessment of Seasonal Influenza A Virus-Specific CD4 T-Cell Responses to 2009 Pandemic H1N1 Swine-Origin Influenza A Virus

Journal of Virology ◽

10.1128/jvi.02226-09 ◽

2010 ◽

Vol 84 (7) ◽

pp. 3312-3319 ◽

Cited By ~ 80

Author(s):

Xinhui Ge ◽

Venus Tan ◽

Paul L. Bollyky ◽

Nathan E. Standifer ◽

Eddie A. James ◽

...

Keyword(s):

T Cells ◽

Influenza Virus ◽

Amino Acid ◽

T Cell ◽

Influenza A Virus ◽

Influenza A ◽

Seasonal Influenza ◽

T Cell Responses ◽

Pandemic H1n1 ◽

Cell Responses

ABSTRACT Very limited evidence has been reported to show human adaptive immune responses to the 2009 pandemic H1N1 swine-origin influenza A virus (S-OIV). We studied 17 S-OIV peptides homologous to immunodominant CD4 T epitopes from hemagglutinin (HA), neuraminidase (NA), nuclear protein (NP), M1 matrix protein (MP), and PB1 of a seasonal H1N1 strain. We concluded that 15 of these 17 S-OIV peptides would induce responses of seasonal influenza virus-specific T cells. Of these, seven S-OIV sequences were identical to seasonal influenza virus sequences, while eight had at least one amino acid that was not conserved. T cells recognizing epitopes derived from these S-OIV antigens could be detected ex vivo. Most of these T cells expressed memory markers, although none of the donors had been exposed to S-OIV. Functional analysis revealed that specific amino acid differences in the sequences of these S-OIV peptides would not affect or partially affect memory T-cell responses. These findings suggest that without protective antibody responses, individuals vaccinated against seasonal influenza A may still benefit from preexisting cross-reactive memory CD4 T cells reducing their susceptibility to S-OIV infection.

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Cloned Defective Interfering Influenza Virus Protects Ferrets from Pandemic 2009 Influenza A Virus and Allows Protective Immunity to Be Established

PLoS ONE ◽

10.1371/journal.pone.0049394 ◽

2012 ◽

Vol 7 (12) ◽

pp. e49394 ◽

Cited By ~ 22

Author(s):

Nigel J. Dimmock ◽

Brian K. Dove ◽

Paul D. Scott ◽

Bo Meng ◽

Irene Taylor ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A Virus ◽

Protective Immunity ◽

Influenza A

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Concurrent comparison of epidemiology, clinical presentation and outcome between adult patients suffering from the pandemic influenza A (H1N1) 2009 virus and the seasonal influenza A virus infection

Postgraduate Medical Journal ◽

10.1136/pgmj.2009.096206 ◽

2010 ◽

Vol 86 (1019) ◽

pp. 515-521 ◽

Cited By ~ 43

Author(s):

K. K. W. To ◽

S. S. Y. Wong ◽

I. W. S. Li ◽

I. F. N. Hung ◽

H. Tse ◽

...

Keyword(s):

Virus Infection ◽

Influenza A Virus ◽

Pandemic Influenza ◽

Influenza A ◽

Seasonal Influenza ◽

Clinical Presentation ◽

Adult Patients ◽

Influenza A H1n1 ◽

Influenza A Virus Infection

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Epidemiological Surveillance of Influenza Virus Matrix Gene in Pigs, in Lagos, Nigeria, 2015-2016

Annals of Science and Technology ◽

10.2478/ast-2018-0001 ◽

2017 ◽

Vol 2 (1) ◽

pp. 1-7

Author(s):

Abdul-Azeez A. Anjorin ◽

Olumuyiwa B. Salu ◽

Akeeb O.B. Oyefolu ◽

Bamidele O. Oke ◽

James B. Ayorinde ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A Virus ◽

Pandemic Influenza ◽

Influenza A ◽

Virus Disease ◽

Influenza Viruses ◽

Epidemiological Surveillance ◽

Viral Gene ◽

Cross Sectional ◽

Matrix Gene

AbstractThe co-infection of different influenza A virus enable viral gene re-assortments especially in pigs that serve as mixing vessel with the possibility of emergence of novel subtypes. Such re-assortants pose serious public health threat, as epitomised by the emergence of pandemic influenza in 2009. In Nigeria, there is mixture of animal species and highly populated densities that can increase the risk of influenza virus endemicity, genetic reshuffling and emergence of future pandemic influenza viruses. Thus, this study was aimed at determining influenza virus disease burden in pigs. This study was a cross sectional molecular surveillance of influenza virus. A total of 194 pig nasal samples from reported cases and randomly sampled were collected from pig farms in Ojo and Ikorodu in Lagos State between October, 2015 and April, 2016. The samples were investigated for the presence of influenza virus matrix gene by Reverse Transcriptase Polymerase Chain Reaction and detected by gel electrophoresis. P-values were calculated using Chi-square and Fisher’s exact tests. The result showed that 25 (12.9%) samples were positive for influenza A virus, out of which, 20 (80%) were samples from Ojo while 5 (20%) were samples from Ikorodu. Epidemiological parameters for the sampled locations, methods either as reported case or randomised, and sex compared were significant at 95% confidence interval. This study determined influenza viral burden in pigs with a molecular prevalence of 12.9% to influenza A. It further confirmed the sub-clinical and clinical circulation of Influenza A virus in pigs in Ojo and Ikorodu in Lagos. Therefore, the detection of influenza A virus in commercial pigs in Nigeria accentuates the importance of continuous surveillance and monitoring of the virus in order to prevent the advent of virulent strains that may spread to Pig-handlers and the community at large.

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Development of DNA-Biochip for Identification of Influenza A Virus Subtypes

Problems of Particularly Dangerous Infections ◽

10.21055/0370-1069-2012-2(112)-89-93 ◽

2012 ◽

pp. 89-93

Author(s):

A. N. Shikov ◽

E. I. Sergeeva ◽

O. K. Demina ◽

V. A. Ternovoy ◽

V. V. Ryabinin ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A Virus ◽

Influenza A ◽

Seasonal Influenza ◽

Highly Pathogenic Avian Influenza ◽

Influenza Viruses ◽

Highly Pathogenic ◽

Influenza Virus A ◽

Pathogenic Avian Influenza ◽

Pathogenic Avian Influenza Virus

Developed was the DNA-biochip to identify subtypes of influenza A virus, pathogenic for humans. Microchip was capable of detecting H1, H3, H5-subtypes of hemagglutinin (including H1-subtype of pandemic A/H1N1(2009) influenza virus ) and neuraminidase subtypes N1,N2 of influenza virus. This microchip was successfully tested on the strains of A/H5N1 highly pathogenic avian influenza virus, A/H1N1(2009) pandemic influenza virus, A/H1N1 and A/H3N2 seasonal influenza viruses.

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