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

2011 ◽  
Vol 18 (9) ◽  
pp. 1401-1405 ◽  
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.

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

2015 ◽  
Vol 89 (20) ◽  
pp. 10602-10611 ◽  
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.

scholarly journals Features of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine

2019 ◽  
Vol 9 (3-4) ◽  
pp. 485-494
Author(s):  
L. M. Tsybalova ◽  
L. A. Stepanova ◽  
A. V. Korotkov ◽  
M. A. Shuklina ◽  
M. V. Zaitseva ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Influenza Virus ◽  
Influenza A Virus ◽  
Cd4 T Cells ◽  
Influenza A ◽  
Influenza Infection ◽  
Sublethal Dose ◽  
Universal Vaccine ◽  
Toll Like Receptor 5

Generating cross-reactive vaccines aimed at targeting all human influenza A virus subtypes is among high priority tasks in contemporary vaccinology. Such vaccines will be primarily demanded during pre-pandemic period as well as used to prime some population cohorts prior to vaccination with standard vaccines containing area-relevant epidemic virus. Unlike routine approach universal vaccines do not induce a sterilizing immunity, but significantly ameliorate overt infection and probable complications. Our study was aimed at evaluating characteristics of immune response in experimental animals primed with a candidate universal vaccine challenged with sublethal influenza A virus infection. Mice were immunized intranasally with the recombinant protein FlgH2-2-4M2e containing conservative peptides derived from two influenza A virus proteins: M2 protein ectodomain and 76–130 amino acid sequence from the second hemagglutinin (HA2) subunit genetically linked to bacterial flagellin protein, which is a ligand for Toll-like receptor 5 (TLR5). Control mice received saline. Two weeks after immunization, mice from both groups were infected with a sublethal dose of A/Aichi/2/68 AN3N2 influenza virus strain. Level of immunoglobulins G and A in the blood sera and bronchoalveolar lavages (BAL) were determined two weeks after immunization and 1 month post infection. Percentage of lung CD4+ T and CD4+ Tem (CD44+CD62L–) cells secreting cytokines TNFα, IFNγ, IL-2 was determined. Immunized vs. control mice responded to sublethal infection with the influenza virus by insignificant weight loss and more pronounced production of vaccine peptide-specific (M2e and aa76–130 HA2) and pan-influenza A/Aichi/2/68 virus IgG and A in the blood sera and BAL. After challenge the number of CD4+ T cells secreting cytokines TNFα and/or IL-2 in immunized mice significantly exceeded counterpart T cells in unimmunized animals that was true for both CD4+T and CD4+ Tem cells. Memory CD4+ T cells were previously shown to play a key role in the prime-boost event and heterosubtypic immune response. Thus, we were able to demonstrate a priming effect for recombinant cross-protective vaccine used in our experiment.

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.

Effect of influenza A virus sow vaccination on infection in pigs at weaning: A prospective longitudinal study

2020 ◽  
Author(s):  
Fabian O. Chamba Pardo ◽  
Matthew Allerson ◽  
Marie Culhane ◽  
Robert Morrison ◽  
Peter Davies ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Influenza A Virus ◽  
Influenza A ◽  
Prospective Longitudinal Study ◽  
Prospective Longitudinal

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

2010 ◽  
Vol 84 (7) ◽  
pp. 3312-3319 ◽  
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.

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

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.

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

2010 ◽  
Vol 202 (7) ◽  
pp. 1011-1020 ◽  
Author(s):  
Karen L. Laurie ◽  
Louise A. Carolan ◽  
Deborah Middleton ◽  
Sue Lowther ◽  
Anne Kelso ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Pandemic Influenza ◽  
Protective Immunity ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Multiple Infections ◽  
H1n1 Pandemic

scholarly journals Preliminary Proteomic Analysis of A549 Cells Infected with Avian Influenza Virus H7N9 and Influenza A Virus H1N1

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0156017 ◽  
Author(s):  
Xiaoman Ding ◽  
Jiahai Lu ◽  
Ruoxi Yu ◽  
Xin Wang ◽  
Ting Wang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Influenza A Virus ◽  
Proteomic Analysis ◽  
Influenza A ◽  
A549 Cells ◽  
Virus H1n1

scholarly journals Development of Two Types of Rapid Diagnostic Test Kits To Detect the Hemagglutinin or Nucleoprotein of the Swine-Origin Pandemic Influenza A Virus H1N1

2011 ◽  
Vol 18 (3) ◽  
pp. 494-499 ◽  
Author(s):  
Rika Mizuike ◽  
Tadahiro Sasaki ◽  
Koichi Baba ◽  
Hisahiko Iwamoto ◽  
Yusuke Shibai ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Virus Detection ◽  
Virus H1n1 ◽  
Viral Hemagglutinin ◽  
Detection Assay ◽  
Influenza A H1n1 ◽  
New Type

ABSTRACTSince its emergence in April 2009, pandemic influenza A virus H1N1 (H1N1 pdm), a new type of influenza A virus with a triple-reassortant genome, has spread throughout the world. Initial attempts to diagnose the infection in patients using immunochromatography (IC) relied on test kits developed for seasonal influenza A and B viruses, many of which proved significantly less sensitive to H1N1 pdm. Here, we prepared monoclonal antibodies that react with H1N1 pdm but not seasonal influenza A (H1N1 and H3N2) or B viruses. Using two of these antibodies, one recognizing viral hemagglutinin (HA) and the other recognizing nucleoprotein (NP), we developed kits for the specific detection of H1N1 pdm and tested them using clinical specimens of nasal wash fluid or nasopharyngeal fluid from patients with influenza-like illnesses. The specificities of both IC test kits were very high (93% for the HA kit, 100% for the NP kit). The test sensitivities for detection of H1N1 pdm were 85.5% with the anti-NP antibody, 49.4% with the anti-HA antibody, and 79.5% with a commercially available influenza A virus detection assay. Use of the anti-NP antibody could allow the rapid and accurate diagnosis of H1N1 pdm infections.

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