Fever following immunization with influenza A (H1N1) vaccine in children : a survey-based study in the Netherlands

NARCIS (Netherlands)

Broos, Nancy; van Puijenbroek, Eugène P; van Grootheest, Kees

2010-01-01

BACKGROUND: In November 2009, all children in the Netherlands from 6 months up to 4 years of age were indicated to receive the Influenza A (H1N1) vaccine. Fever is a common adverse event following immunization in children. Pandemrix®, an inactivated, split-virus influenza A (H1N1) vaccine, was used

Immune protection induced on day 10 following administration of the 2009 A/H1N1 pandemic influenza vaccine.

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Yizhuo Sun

Full Text Available BACKGROUND: The 2009 swine-origin influenza virus (S-OIV H1N1 pandemic has caused more than 18,000 deaths worldwide. Vaccines against the 2009 A/H1N1 influenza virus are useful for preventing infection and controlling the pandemic. The kinetics of the immune response following vaccination with the 2009 A/H1N1 influenza vaccine need further investigation. METHODOLOGY/PRINCIPAL FINDINGS: 58 volunteers were vaccinated with a 2009 A/H1N1 pandemic influenza monovalent split-virus vaccine (15 µg, single-dose. The sera were collected before Day 0 (pre-vaccination and on Days 3, 5, 10, 14, 21, 30, 45 and 60 post vaccination. Specific antibody responses induced by the vaccination were analyzed using hemagglutination inhibition (HI assay and enzyme-linked immunosorbent assay (ELISA. After administration of the 2009 A/H1N1 influenza vaccine, specific and protective antibody response with a major subtype of IgG was sufficiently developed as early as Day 10 (seroprotection rate: 93%. This specific antibody response could maintain for at least 60 days without significant reduction. Antibody response induced by the 2009 A/H1N1 influenza vaccine could not render protection against seasonal H1N1 influenza (seroconversion rate: 3% on Day 21. However, volunteers with higher pre-existing seasonal influenza antibody levels (pre-vaccination HI titer ≥1∶40, Group 1 more easily developed a strong antibody protection effect against the 2009 A/H1N1 influenza vaccine as compared with those showing lower pre-existing seasonal influenza antibody levels (pre-vaccination HI titer <1∶40, Group 2. The titer of the specific antibody against the 2009 A/H1N1 influenza was much higher in Group 1 (geometric mean titer: 146 on Day 21 than that in Group 2 (geometric mean titer: 70 on Day 21. CONCLUSIONS/SIGNIFICANCE: Recipients could gain sufficient protection as early as 10 days after vaccine administration. The protection could last at least 60 days. Individuals with a

Induction of long-term protective immune responses by influenza H5N1 virus-like particles.

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Sang-Moo Kang

Full Text Available Recurrent outbreaks of highly pathogenic H5N1 avian influenza virus pose a threat of eventually causing a pandemic. Early vaccination of the population would be the single most effective measure for the control of an emerging influenza pandemic.Influenza virus-like particles (VLPs produced in insect cell-culture substrates do not depend on the availability of fertile eggs for vaccine manufacturing. We produced VLPs containing influenza A/Viet Nam1203/04 (H5N1 hemagglutinin, neuraminidase, and matrix proteins, and investigated their preclinical immunogenicity and protective efficacy. Mice immunized intranasally with H5N1 VLPs developed high levels of H5N1 specific antibodies and were 100% protected against a high dose of homologous H5N1 virus infection at 30 weeks after immunization. Protection is likely to be correlated with humoral and cellular immunologic memory at systemic and mucosal sites as evidenced by rapid anamnestic responses to re-stimulation with viral antigen in vivo and in vitro.These results provide support for clinical evaluation of H5N1 VLP vaccination as a public health intervention to mitigate a possible pandemic of H5N1 influenza.

Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus.

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Kreijtz, J H C M; Bodewes, R; van den Brand, J M A; de Mutsert, G; Baas, C; van Amerongen, G; Fouchier, R A M; Osterhaus, A D M E; Rimmelzwaan, G F

2009-08-06

The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1). Prior infection with influenza virus A/Hong Kong/2/68 reduced clinical signs, body weight loss, mortality and virus replication in the lungs as compared to naive mice infected with HPAI virus A/Indonesia/5/05. Priming by infection with respiratory syncytial virus, a non-related virus did not have a beneficial effect on the outcome of A/H5N1 infections, indicating that adaptive immune responses were responsible for the protective effect. In mice primed by infection with influenza A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM and PA(224-232) SCLENFRAYV were observed. A small proportion of these CTL was cross-reactive with the peptide variant derived from the influenza A/H5N1 virus (ASNENMEVM and SSLENFRAYV respectively) and upon challenge infection with the influenza A/H5N1 virus cross-reactive CTL were selectively expanded. These CTL, in addition to those directed to conserved epitopes, shared by the influenza A/H3N2 and A/H5N1 viruses, most likely contributed to accelerated clearance of the influenza A/H5N1 virus infection. Although also other arms of the adaptive immune response may contribute to heterosubtypic immunity, the induction of virus-specific CTL may be an attractive target for development of broad protective vaccines. Furthermore the

Risk factors and immunity in a nationally representative population following the 2009 influenza A(H1N1 pandemic.

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Don Bandaranayake

Full Text Available BACKGROUND: Understanding immunity, incidence and risk factors of the 2009 influenza A(H1N1 pandemic (2009 H1N1 through a national seroprevalence study is necessary for informing public health interventions and disease modelling. METHODS AND FINDINGS: We collected 1687 serum samples and individual risk factor data between November-2009 to March-2010, three months after the end of the 2009 H1N1 wave in New Zealand. Participants were randomly sampled from selected general practices countrywide and hospitals in the Auckland region. Baseline immunity was measured from 521 sera collected during 2004 to April-2009. Haemagglutination inhibition (HI antibody titres of ≥1:40 against 2009 H1N1 were considered seroprotective as well as seropositive. The overall community seroprevalence was 26.7% (CI:22.6-29.4. The seroprevalence varied across age and ethnicity. Children aged 5-19 years had the highest seroprevalence (46.7%;CI:38.3-55.0, a significant increase from the baseline (14%;CI:7.2-20.8. Older adults aged ≥60 had no significant difference in seroprevalence between the serosurvey (24.8%;CI:18.7-30.9 and baseline (22.6%;CI:15.3-30.0. Pacific peoples had the highest seroprevalence (49.5%;CI:35.1-64.0. There was no significant difference in seroprevalence between both primary (29.6%;CI:22.6-36.5 and secondary healthcare workers (25.3%;CI:20.8-29.8 and community participants. No significant regional variation was observed. Multivariate analysis indicated age as the most important risk factor followed by ethnicity. Previous seasonal influenza vaccination was associated with higher HI titres. Approximately 45.2% of seropositive individuals reported no symptoms. CONCLUSIONS: Based on age and ethnicity standardisation to the New Zealand Population, about 29.5% of New Zealanders had antibody titers at a level consistent with immunity to 2009 H1N1. Around 18.3% of New Zealanders were infected with the virus during the first wave including about one child

Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades

DEFF Research Database (Denmark)

Bragstad, Karoline; Martel, Cyril; Thomsen, Joakim S.

2011-01-01

Please cite this paper as: Bragstad et al. (2010) Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades. Influenza and Other Respiratory Viruses 5(1), 13-23. Background Alternative influenza vaccines...... and vaccine production forms are needed as the conventional protein vaccines do not induce broad cross-reactivity against drifted strains. Furthermore, fast vaccine production is especially important in a pandemic situation, and broader vaccine reactivity would diminish the need for frequent change...... in the vaccine formulations. Objective In this study, we compared the ability of pandemic influenza DNA vaccines to induce immunity against distantly related strains within a subtype with the immunity induced by conventional trivalent protein vaccines against homologous virus challenge. Methods Ferrets were...

A pandemic influenza H1N1 live vaccine based on modified vaccinia Ankara is highly immunogenic and protects mice in active and passive immunizations.

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Annett Hessel

Full Text Available BACKGROUND: The development of novel influenza vaccines inducing a broad immune response is an important objective. The aim of this study was to evaluate live vaccines which induce both strong humoral and cell-mediated immune responses against the novel human pandemic H1N1 influenza virus, and to show protection in a lethal animal challenge model. METHODOLOGY/PRINCIPAL FINDINGS: For this purpose, the hemagglutinin (HA and neuraminidase (NA genes of the influenza A/California/07/2009 (H1N1 strain (CA/07 were inserted into the replication-deficient modified vaccinia Ankara (MVA virus--a safe poxviral live vector--resulting in MVA-H1-Ca and MVA-N1-Ca vectors. These live vaccines, together with an inactivated whole virus vaccine, were assessed in a lung infection model using immune competent Balb/c mice, and in a lethal challenge model using severe combined immunodeficient (SCID mice after passive serum transfer from immunized mice. Balb/c mice vaccinated with the MVA-H1-Ca virus or the inactivated vaccine were fully protected from lung infection after challenge with the influenza H1N1 wild-type strain, while the neuraminidase virus MVA-N1-Ca induced only partial protection. The live vaccines were already protective after a single dose and induced substantial amounts of neutralizing antibodies and of interferon-gamma-secreting (IFN-gamma CD4- and CD8 T-cells in lungs and spleens. In the lungs, a rapid increase of HA-specific CD4- and CD8 T cells was observed in vaccinated mice shortly after challenge with influenza swine flu virus, which probably contributes to the strong inhibition of pulmonary viral replication observed. In addition, passive transfer of antisera raised in MVA-H1-Ca vaccinated immune-competent mice protected SCID mice from lethal challenge with the CA/07 wild-type virus. CONCLUSIONS/SIGNIFICANCE: The non-replicating MVA-based H1N1 live vaccines induce a broad protective immune response and are promising vaccine candidates for

Memory immune responses against pandemic (H1N1 2009 influenza virus induced by a whole particle vaccine in cynomolgus monkeys carrying Mafa-A1*052:02.

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Masahiko Arikata

Full Text Available We made an H1N1 vaccine candidate from a virus library consisting of 144 ( = 16 HA×9 NA non-pathogenic influenza A viruses and examined its protective effects against a pandemic (2009 H1N1 strain using immunologically naïve cynomolgus macaques to exclude preexisting immunity and to employ a preclinical study since preexisting immunity in humans previously vaccinated or infected with influenza virus might make comparison of vaccine efficacy difficult. Furthermore, macaques carrying a major histocompatibility complex class I molecule, Mafa-A1*052:02, were used to analyze peptide-specific CD8(+ T cell responses. Sera of macaques immunized with an inactivated whole particle formulation without addition of an adjuvant showed higher neutralization titers against the vaccine strain A/Hokkaido/2/1981 (H1N1 than did sera of macaques immunized with a split formulation. Neutralization activities against the pandemic strain A/Narita/1/2009 (H1N1 in sera of macaques immunized twice with the split vaccine reached levels similar to those in sera of macaques immunized once with the whole particle vaccine. After inoculation with the pandemic virus, the virus was detected in nasal samples of unvaccinated macaques for 6 days after infection and for 2.67 days and 5.33 days on average in macaques vaccinated with the whole particle vaccine and the split vaccine, respectively. After the challenge infection, recall neutralizing antibody responses against the pandemic virus and CD8(+ T cell responses specific for nucleoprotein peptide NP262-270 bound to Mafa-A1*052:02 in macaques vaccinated with the whole particle vaccine were observed more promptly or more vigorously than those in macaques vaccinated with the split vaccine. These findings demonstrated that the vaccine derived from our virus library was effective for pandemic virus infection in macaques and that the whole particle vaccine conferred more effective memory and broader cross-reactive immune responses

New Orf virus (Parapoxvirus) recombinant expressing H5 hemagglutinin protects mice against H5N1 and H1N1 influenza A virus.

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Rohde, Jörg; Amann, Ralf; Rziha, Hanns-Joachim

2013-01-01

Previously we demonstrated the versatile utility of the Parapoxvirus Orf virus (ORFV) as a vector platform for the development of potent recombinant vaccines. In this study we present the generation of new ORFV recombinants expressing the hemagglutinin (HA) or nucleoprotein (NP) of the highly pathogenic avian influenza virus (HPAIV) H5N1. Correct foreign gene expression was examined in vitro by immunofluorescence, Western blotting and flow cytometry. The protective potential of both recombinants was evaluated in the mouse challenge model. Despite adequate expression of NP, the recombinant D1701-V-NPh5 completely failed to protect mice from lethal challenge. However, the H5 HA-expressing recombinant D1701-V-HAh5n mediated solid protection in a dose-dependent manner. Two intramuscular (i.m.) injections of the HA-expressing recombinant protected all animals from lethal HPAIV infection without loss of body weight. Notably, the immunized mice resisted cross-clade H5N1 and heterologous H1N1 (strain PR8) influenza virus challenge. In vivo antibody-mediated depletion of CD4-positive and/or CD8-posititve T-cell subpopulations during immunization and/or challenge infection implicated the relevance of CD4-positive T-cells for induction of protective immunity by D1701-V-HAh5n, whereas the absence of CD8-positive T-cells did not significantly influence protection. In summary, this study validates the potential of the ORFV vectored vaccines also to combat HPAIV.

New Orf virus (Parapoxvirus recombinant expressing H5 hemagglutinin protects mice against H5N1 and H1N1 influenza A virus.

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Jörg Rohde

Full Text Available Previously we demonstrated the versatile utility of the Parapoxvirus Orf virus (ORFV as a vector platform for the development of potent recombinant vaccines. In this study we present the generation of new ORFV recombinants expressing the hemagglutinin (HA or nucleoprotein (NP of the highly pathogenic avian influenza virus (HPAIV H5N1. Correct foreign gene expression was examined in vitro by immunofluorescence, Western blotting and flow cytometry. The protective potential of both recombinants was evaluated in the mouse challenge model. Despite adequate expression of NP, the recombinant D1701-V-NPh5 completely failed to protect mice from lethal challenge. However, the H5 HA-expressing recombinant D1701-V-HAh5n mediated solid protection in a dose-dependent manner. Two intramuscular (i.m. injections of the HA-expressing recombinant protected all animals from lethal HPAIV infection without loss of body weight. Notably, the immunized mice resisted cross-clade H5N1 and heterologous H1N1 (strain PR8 influenza virus challenge. In vivo antibody-mediated depletion of CD4-positive and/or CD8-posititve T-cell subpopulations during immunization and/or challenge infection implicated the relevance of CD4-positive T-cells for induction of protective immunity by D1701-V-HAh5n, whereas the absence of CD8-positive T-cells did not significantly influence protection. In summary, this study validates the potential of the ORFV vectored vaccines also to combat HPAIV.

Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

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Grgić, Helena; Costa, Marcio; Friendship, Robert M; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

2015-01-01

The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

Reasons for Low Pandemic H1N1 2009 Vaccine Acceptance within a College Sample

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Russell D. Ravert

2012-01-01

Full Text Available This study examined health beliefs associated with novel influenza A (H1N1 immunization among US college undergraduates during the 2009-2010 pandemic. Undergraduates (ages 18–24 years from a large Midwestern University were invited to complete an online survey during March, 2010, five months after H1N1 vaccines became available. Survey items measured H1N1 vaccine history and H1N1-related attitudes based on the health belief literature. Logistic regression was used to identify attitudes associated with having received an H1N1 vaccine, and thematic analysis of student comments was conducted to further understand influences on vaccine decisions. Among the 296 students who participated in the survey, 15.2% reported having received an H1N1 vaccine. In regression analysis, H1N1 immunization was associated with seasonal flu vaccine history, perceived vaccine effectiveness, perceived obstacles to vaccination, and vaccine safety concerns. Qualitative results illustrate the relationship of beliefs to vaccine decisions, particularly in demonstrating that students often held concerns that vaccine could cause H1N1 or side effects. Vaccine safety, efficacy, and obstacles to immunization were major considerations in deciding whether to accept the H1N1 pandemic vaccine. Therefore, focusing on those aspects might be especially useful in future vaccine efforts within the college population.

Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus.

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Yasui, Fumihiko; Itoh, Yasushi; Ikejiri, Ai; Kitabatake, Masahiro; Sakaguchi, Nobuo; Munekata, Keisuke; Shichinohe, Shintaro; Hayashi, Yukiko; Ishigaki, Hirohito; Nakayama, Misako; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa; Kohara, Michinori

2016-11-28

H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.

Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

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Helena Grgić

Full Text Available The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1pdm09. One H1N2 isolate had hemagglutinin (HA, polymerase A (PA and non-structural (NS genes closely related to A(H1N1pdm09, and neuraminidase (NA, matrix (M, polymerase B1 (PB1, polymerase B2 (PB2, and nucleoprotein (NP genes originating from a triple-reassortant H3N2 virus (tr H3N2. The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

Linear DNA vaccine prepared by large-scale PCR provides protective immunity against H1N1 influenza virus infection in mice.

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Wang, Fei; Chen, Quanjiao; Li, Shuntang; Zhang, Chenyao; Li, Shanshan; Liu, Min; Mei, Kun; Li, Chunhua; Ma, Lixin; Yu, Xiaolan

2017-06-01

Linear DNA vaccines provide effective vaccination. However, their application is limited by high cost and small scale of the conventional polymerase chain reaction (PCR) generally used to obtain sufficient amounts of DNA effective against epidemic diseases. In this study, a two-step, large-scale PCR was established using a low-cost DNA polymerase, RKOD, expressed in Pichia pastoris. Two linear DNA vaccines encoding influenza H1N1 hemagglutinin (HA) 1, LEC-HA, and PTO-LEC-HA (with phosphorothioate-modified primers), were produced by the two-step PCR. Protective effects of the vaccines were evaluated in a mouse model. BALB/c mice were immunized three times with the vaccines or a control DNA fragment. All immunized animals were challenged by intranasal administration of a lethal dose of influenza H1N1 virus 2 weeks after the last immunization. Sera of the immunized animals were tested for the presence of HA-specific antibodies, and the total IFN-γ responses induced by linear DNA vaccines were measured. The results showed that the DNA vaccines but not the control DNA induced strong antibody and IFN-γ responses. Additionally, the PTO-LEC-HA vaccine effectively protected the mice against the lethal homologous mouse-adapted virus, with a survival rate of 100% versus 70% in the LEC-HA-vaccinated group, showing that the PTO-LEC-HA vaccine was more effective than LEC-HA. In conclusion, the results indicated that the linear H1N1 HA-coding DNA vaccines induced significant immune responses and protected mice against a lethal virus challenge. Thus, the low-cost, two-step, large-scale PCR can be considered a potential tool for rapid manufacturing of linear DNA vaccines against emerging infectious diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

The impact of immunosenescence on humoral immune response variation after influenza A/H1N1 vaccination in older subjects.

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Iana H Haralambieva

Full Text Available Although influenza causes significant morbidity and mortality in the elderly, the factors underlying the reduced vaccine immunogenicity and efficacy in this age group are not completely understood. Age and immunosenescence factors, and their impact on humoral immunity after influenza vaccination, are of growing interest for the development of better vaccines for the elderly.We assessed associations between age and immunosenescence markers (T cell receptor rearrangement excision circles - TREC content, peripheral white blood cell telomerase - TERT expression and CD28 expression on T cells and influenza A/H1N1 vaccine-induced measures of humoral immunity in 106 older subjects at baseline and three timepoints post-vaccination.TERT activity (TERT mRNA expression was significantly positively correlated with the observed increase in the influenza-specific memory B cell ELISPOT response at Day 28 compared to baseline (p-value=0.025. TREC levels were positively correlated with the baseline and early (Day 3 influenza A/H1N1-specific memory B cell ELISPOT response (p-value=0.042 and p-value=0.035, respectively. The expression and/or expression change of CD28 on CD4+ and/or CD8+ T cells at baseline and Day 3 was positively correlated with the influenza A/H1N1-specific memory B cell ELISPOT response at baseline, Day 28 and Day 75 post-vaccination. In a multivariable analysis, the peak antibody response (HAI and/or VNA at Day 28 was negatively associated with age, the percentage of CD8+CD28 low T cells, IgD+CD27- naïve B cells, and percentage overall CD20- B cells and plasmablasts, measured at Day 3 post-vaccination. The early change in influenza-specific memory B cell ELISPOT response was positively correlated with the observed increase in influenza A/H1N1-specific HAI antibodies at Day 28 and Day 75 relative to baseline (p-value=0.007 and p-value=0.005, respectively.Our data suggest that influenza-specific humoral immunity is significantly influenced by

Mucosal immunity induced by adenovirus-based H5N1 HPAI vaccine confers protection against a lethal H5N2 avian influenza virus challenge

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Park, Ki Seok; Lee, Jiyeung; Ahn, So Shin; Byun, Young-Ho; Seong, Baik Lin; Baek, Yun Hee; Song, Min-Suk; Choi, Young Ki; Na, Yun Jeong; Hwang, Inhwan; Sung, Young Chul; Lee, Chang Geun

2009-01-01

Development of effective vaccines against highly pathogenic avian influenza (HPAI) H5N1 viruses is a global public health priority. Considering the difficulty in predicting HPAI H5N1 pandemic strains, one strategy used in their design includes the development of formulations with the capacity of eliciting broad cross-protective immunity against multiple viral antigens. To this end we constructed a replication-defective recombinant adenovirus-based avian influenza virus vaccine (rAdv-AI) expressing the codon-optimized M2eX-HA-hCD40L and the M1-M2 fusion genes from HPAI H5N1 human isolate. Although there were no significant differences in the systemic immune responses observed between the intramuscular prime-intramuscular boost regimen (IM/IM) and the intranasal prime-intramuscular boost regimen (IN/IM), IN/IM induced more potent CD8 + T cell and antibody responses at mucosal sites than the IM/IM vaccination, resulting in more effective protection against lethal H5N2 avian influenza (AI) virus challenge. These findings suggest that the strategies used to induce multi-antigen-targeted mucosal immunity, such as IN/IM delivery of rAdv-AI, may be a promising approach for developing broad protective vaccines that may be more effective against the new HPAI pandemic strains.

Cytokine response patterns in severe pandemic 2009 H1N1 and seasonal influenza among hospitalized adults.

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Nelson Lee

Full Text Available BACKGROUND: Studying cytokine/chemokine responses in severe influenza infections caused by different virus subtypes may improve understanding on pathogenesis. METHODS: Adults hospitalized for laboratory-confirmed seasonal and pandemic 2009 A/H1N1 (pH1N1 influenza were studied. Plasma concentrations of 13 cytokines/chemokines were measured at presentation and then serially, using cytometric-bead-array with flow-cytometry and ELISA. PBMCs from influenza patients were studied for cytokine/chemokine expression using ex-vivo culture (Whole Blood Assay,±PHA/LPS stimulation. Clinical variables were prospectively recorded and analyzed. RESULTS: 63 pH1N1 and 53 seasonal influenza patients were studied. pH1N1 patients were younger (mean±S.D. 42.8±19.2 vs 70.5±16.7 years, and fewer had comorbidities. Respiratory/cardiovascular complications were common in both groups (71.4% vs 81.1%, although severe pneumonia with hypoxemia (54.0% vs 28.3% and ICU admissions (25.4% vs 1.9% were more frequent with pH1N1. Hyperactivation of the proinflammatory cytokines IL-6, CXCL8/IL-8, CCL2/MCP-1 and sTNFR-1 was found in pH1N1 pneumonia (2-15 times normal and in complicated seasonal influenza, but not in milder pH1N1 infections. The adaptive-immunity (Th1/Th17-related CXCL10/IP-10, CXCL9/MIG and IL-17A however, were markedly suppressed in severe pH1N1 pneumonia (2-27 times lower than seasonal influenza; P-values<0.01. This pattern was further confirmed with serial measurements. Hypercytokinemia tended to be sustained in pH1N1 pneumonia, associated with a slower viral clearance [PCR-negativity: day 3-4, 55% vs 85%; day 6-7, 67% vs 100%]. Elevated proinflammatory cytokines, particularly IL-6, predicted ICU admission (adjusted OR 12.6, 95%CI 2.6-61.5, per log(10unit increase; P = 0.002, and correlated with fever, tachypnoea, deoxygenation, and length-of-stay (Spearman's rho, P-values<0.01 in influenza infections. PBMCs in seasonal influenza patients were activated and

Evolutionary trends of A(H1N1 influenza virus hemagglutinin since 1918.

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Jun Shen

2009-11-01

Full Text Available The Pandemic (H1N1 2009 is spreading to numerous countries and causing many human deaths. Although the symptoms in humans are mild at present, fears are that further mutations in the virus could lead to a potentially more dangerous outbreak in subsequent months. As the primary immunity-eliciting antigen, hemagglutinin (HA is the major agent for host-driven antigenic drift in A(H3N2 virus. However, whether and how the evolution of HA is influenced by existing immunity is poorly understood for A(H1N1. Here, by analyzing hundreds of A(H1N1 HA sequences since 1918, we show the first evidence that host selections are indeed present in A(H1N1 HAs. Among a subgroup of human A(H1N1 HAs between 1918 approximately 2008, we found strong diversifying (positive selection at HA(1 156 and 190. We also analyzed the evolutionary trends at HA(1 190 and 225 that are critical determinants for receptor-binding specificity of A(H1N1 HA. Different A(H1N1 viruses appeared to favor one of these two sites in host-driven antigenic drift: epidemic A(H1N1 HAs favor HA(1 190 while the 1918 pandemic and swine HAs favor HA(1 225. Thus, our results highlight the urgency to understand the interplay between antigenic drift and receptor binding in HA evolution, and provide molecular signatures for monitoring future antigenically drifted 2009 pandemic and seasonal A(H1N1 influenza viruses.

Leptin and leptin-related gene polymorphisms, obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals.

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Ovsyannikova, Inna G; White, Sarah J; Larrabee, Beth R; Grill, Diane E; Jacobson, Robert M; Poland, Gregory A

2014-02-07

Obesity is a risk factor for complicated influenza A/H1N1 disease and poor vaccine immunogenicity. Leptin, an adipocyte-derived hormone/cytokine, has many immune regulatory functions and therefore could explain susceptibility to infections and poor vaccine outcomes. We recruited 159 healthy adults (50-74 years old) who were immunized with inactivated TIV influenza vaccine that contained A/California/7/2009/H1N1 virus. We found a strong correlation between leptin concentration and BMI (r=0.55, pGHRL genes that were associated with leptin levels and four SNPs in the PTPN1/LEPR/STAT3 genes associated with peripheral blood TREC levels (p<0.05). Heterozygosity of the synonymous variant rs2230604 in the PTPN1 gene was associated with a significantly lower (531 vs. 259, p=0.005) TREC level, as compared to the homozygous major variant. We also found eight SNPs in the LEP/PPARG/CRP genes associated with variations in influenza-specific HAI and B-cell responses (p<0.05). Our results suggest that specific allelic variations in the leptin-related genes may influence adaptive immune responses to influenza vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.

Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens

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Pushko, Peter; Tretyakova, Irina; Hidajat, Rachmat; Zsak, Aniko; Chrzastek, Klaudia; Tumpey, Terrence M.; Kapczynski, Darrell R.

2017-01-01

Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. - Highlights: •VLPs were prepared that co-localized H5, H7 and H9 subtypes in a VLP envelope. •VLPs were characterized including electron microscopy, HA assay and NA enzyme activity. •Experimental VLP vaccine was evaluated in an avian influenza challenge model. •VLPs induced immune responses against heterologous H5, H7 and H9 virus challenges.

Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens

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Pushko, Peter, E-mail: ppushko@medigen-usa.com [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States); Tretyakova, Irina; Hidajat, Rachmat [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States); Zsak, Aniko; Chrzastek, Klaudia [USDA SEPRL, 934 College Station Rd, Athens, GA (United States); Tumpey, Terrence M. [Influenza Division, CDC,1600 Clifton Road N.E., Atlanta, GA (United States); Kapczynski, Darrell R. [USDA SEPRL, 934 College Station Rd, Athens, GA (United States)

2017-01-15

Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. - Highlights: •VLPs were prepared that co-localized H5, H7 and H9 subtypes in a VLP envelope. •VLPs were characterized including electron microscopy, HA assay and NA enzyme activity. •Experimental VLP vaccine was evaluated in an avian influenza challenge model. •VLPs induced immune responses against heterologous H5, H7 and H9 virus challenges.

Protection of guinea pigs by vaccination with a recombinant swinepox virus co-expressing HA1 genes of swine H1N1 and H3N2 influenza viruses.

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Xu, Jiarong; Yang, Deji; Huang, Dongyan; Xu, Jiaping; Liu, Shichao; Lin, Huixing; Zhu, Haodan; Liu, Bao; Lu, Chengping

2013-03-01

Swine influenza (SI) is an acute respiratory infectious disease of swine caused by swine influenza virus (SIV). SIV is not only an important respiratory pathogen in pigs but also a potent threat to human health. Here, we report the construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs. Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and H3N2. The IFN-γ and IL-4 concentrations in the supernatant of lymphocytes stimulated with purified SIV HA1 antigen were significantly higher (P guinea pigs against SIV H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung lesions. However, the control guinea pigs experienced distinct gross and micrographic lung lesions at 7 days post-challenge. Our data suggest that the recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.

Mongrelised genetics of H1N1 virus: A bird′s eyeview

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Nagarathna C

2010-01-01

Full Text Available H1N1 influenza, also known as "novel H1N1 virus" has led to a "global outcry." This virus is more virulent when compared with other seasonal flu viruses. Virulence may change as the adaptive mutation gene increases within the virus. A study at the US Centre for Disease Control and Prevention published in May 2009 found that children had no preexisting immunity to the new strain as they showed no cross-reactive antibody reaction when compared with adults aged 18-64 years, who showed a cross-reactive antibody reaction of 6-9% and older adults with 33% immunity. This review article depicts H1N1 virus, its virulence with genetic evolution potential and preventive protocol for the dental professionals. This would allow us to comprehend the changes in the disease process and contribute in its prevention as "prevention is better than cure."

Humans and ferrets with prior H1N1 influenza virus infections do not exhibit evidence of original antigenic sin after infection or vaccination with the 2009 pandemic H1N1 influenza virus.

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O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J; Subbarao, Kanta

2014-05-01

The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus.

Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus.

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Busquets, Núria; Segalés, Joaquim; Córdoba, Lorena; Mussá, Tufaria; Crisci, Elisa; Martín-Valls, Gerard E; Simon-Grifé, Meritxell; Pérez-Simó, Marta; Pérez-Maíllo, Monica; Núñez, Jose I; Abad, Francesc X; Fraile, Lorenzo; Pina, Sonia; Majó, Natalia; Bensaid, Albert; Domingo, Mariano; Montoya, María

2010-01-01

The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains. © INRA, EDP Sciences, 2010.

Immune response after one or two doses of pandemic influenza A (H1N1) monovalent, AS03-adjuvanted vaccine in HIV infected adults

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Bybeck Nielsen, Allan; Nielsen, Henriette Schjønning; Nielsen, Lars

2012-01-01

INTRODUCTION: Continued research is needed to evaluate and improve the immunogenicity of influenza vaccines in HIV infected patients. We aimed to determine the antibody responses after one or two doses of the AS03-adjuvanted pandemic influenza A (H1N1) vaccine in HIV infected patients. METHOD......: Following the influenza season 2009/2010, 219 HIV infected patients were included and divided into three groups depending on whether they received none (n=60), one (n=31) or two (n=128) doses of pandemic influenza A (H1N1) vaccine. At inclusion, antibody titers for all patients were analyzed and compared...... to pre-pandemic antibody titers analyzed from serum samples in a local storage facility. RESULTS: 4-9 months after a single immunization, we found a seroprotection rate of 77.4% and seroconversion rate of 67.7%. After two immunizations the rates increased significantly to seroprotection rate of 97...

Influence of maternal immunity on vaccine efficacy and susceptibility of one day old chicks against Egyptian highly pathogenic avian influenza H5N1.

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Abdelwhab, E M; Grund, Christian; Aly, Mona M; Beer, Martin; Harder, Timm C; Hafez, Hafez M

2012-02-24

In Egypt, continuous circulation of highly pathogenic avian influenza (HPAI) H5N1 viruses of clade 2.2.1 in vaccinated commercial poultry challenges strenuous control efforts. Here, vaccine-derived maternal AIV H5 specific immunity in one-day old chicks was investigated as a factor of vaccine failure in long-term blanket vaccination campaigns in broiler chickens. H5 seropositive one-day old chicks were derived from breeders repeatedly immunized with a commercial inactivated vaccine based on the Potsdam/H5N2 strain. When challenged using the antigenically related HPAIV strain Italy/98 (H5N2) clinical protection was achieved until at least 10 days post-hatch although virus replication was not fully suppressed. No protection at all was observed against the Egyptian HPAIV strain EGYvar/H5N1 representing a vaccine escape lineage. Other groups of chicks with maternal immunity were vaccinated once at 3 or 14 days of age using either the Potsdam/H5N2 vaccine or a vaccine based on EGYvar/H5N1. At day 35 of age these chicks were challenged with the Egyptian HPAIV strain EGYcls/H5N1 which co-circulates with EGYvar/H5N1 but does not represent an antigenic drift variant. The Potsdam/H5N2 vaccinated groups were not protected against EGYcls/H5N1 infection while, in contrast, the EGYvar/H5N1 vaccinated chicks withstand challenge with EGYvar/H5N1 infection. In addition, the results showed that maternal antibodies could interfere with the immune response when a homologous vaccine strain was used. Copyright © 2011. Published by Elsevier B.V.

Effect of simultaneous vaccination with H1N1 and GAD-alum on GAD65-induced immune response.

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Tavira, Beatriz; Cheramy, Mikael; Axelsson, Stina; Åkerman, Linda; Ludvigsson, Johnny; Casas, Rosaura

2017-07-01

A European Phase III trial of GAD formulated with aluminium hydroxide (GAD-alum) failed to reach its primary endpoint (preservation of stimulated C-peptide secretion from baseline to 15 months in type 1 diabetes patients), but subgroup analysis showed a clinical effect when participants from Nordic countries were excluded, raising concern as to whether the mass vaccination of the Swedish and Finnish populations with the Pandemrix influenza vaccine could have influenced the study outcomes. In the current study, we aimed to assess whether Pandemrix vaccination affects the specific immune responses induced by GAD-alum and the C-peptide response. In this secondary analysis, we analysed data acquired from the Swedish participants in the Phase III GAD-alum trial who received subcutaneous GAD-alum vaccination (two doses, n = 43; four doses, n = 46) or placebo (n = 48). GAD autoantibodies (GADA) and H1N1 autoantibodies, GAD 65 -induced cytokine secretion and change in fasting and stimulated C-peptide levels from baseline to 15 months were analysed with respect to the relative time between H1N1 vaccination and the first injection of GAD-alum. GADA levels at 15 months were associated with the relative time between GAD-alum and Pandemrix administration in participants who received two doses of the GAD-alum vaccine (p = 0.015, r = 0.4). Both in participants treated with two doses and four doses of GAD-alum, GADA levels were higher when the relative time between vaccines was ≥210 days (p < 0.05). In the group that received two doses of GAD-alum, levels of several GAD 65 -induced cytokines were higher in participants who received the H1N1 vaccination and the first GAD-alum injection at least 150 days apart, and the change in fasting and stimulated C-peptide at 15 months was associated with the relative time between vaccines. Neither of these effects were observed in individuals who received four doses of GAD-alum. In individuals who received two doses of GAD

Detection of extensive cross-neutralization between pandemic and seasonal A/H1N1 Influenza Viruses using a pseudotype neutralization assay.

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Béatrice Labrosse

Full Text Available BACKGROUND: Cross-immunity between seasonal and pandemic A/H1N1 influenza viruses remains uncertain. In particular, the extent that previous infection or vaccination by seasonal A/H1N1 viruses can elicit protective immunity against pandemic A/H1N1 is unclear. METHODOLOGY/PRINCIPAL FINDINGS: Neutralizing titers against seasonal A/H1N1 (A/Brisbane/59/2007 and against pandemic A/H1N1 (A/California/04/2009 were measured using an HIV-1-based pseudovirus neutralization assay. Using this highly sensitive assay, we found that a large fraction of subjects who had never been exposed to pandemic A/H1N1 express high levels of pandemic A/H1N1 neutralizing titers. A significant correlation was seen between neutralization of pandemic A/H1N1 and neutralization of a standard seasonal A/H1N1 strain. Significantly higher pandemic A/H1N1 neutralizing titers were measured in subjects who had received vaccination against seasonal influenza in 2008-2009. Higher pandemic neutralizing titers were also measured in subjects over 60 years of age. CONCLUSIONS/SIGNIFICANCE: Our findings reveal that the extent of protective cross-immunity between seasonal and pandemic A/H1N1 influenza viruses may be more important than previously estimated. This cross-immunity could provide a possible explanation of the relatively mild profile of the recent influenza pandemic.

Cross-protection against European swine influenza viruses in the context of infection immunity against the 2009 pandemic H1N1 virus: studies in the pig model of influenza.

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Qiu, Yu; De Hert, Karl; Van Reeth, Kristien

2015-09-24

Pigs are natural hosts for the same influenza virus subtypes as humans and are a valuable model for cross-protection studies with influenza. In this study, we have used the pig model to examine the extent of virological protection between a) the 2009 pandemic H1N1 (pH1N1) virus and three different European H1 swine influenza virus (SIV) lineages, and b) these H1 viruses and a European H3N2 SIV. Pigs were inoculated intranasally with representative strains of each virus lineage with 6- and 17-week intervals between H1 inoculations and between H1 and H3 inoculations, respectively. Virus titers in nasal swabs and/or tissues of the respiratory tract were determined after each inoculation. There was substantial though differing cross-protection between pH1N1 and other H1 viruses, which was directly correlated with the relatedness in the viral hemagglutinin (HA) and neuraminidase (NA) proteins. Cross-protection against H3N2 was almost complete in pigs with immunity against H1N2, but was weak in H1N1/pH1N1-immune pigs. In conclusion, infection with a live, wild type influenza virus may offer substantial cross-lineage protection against viruses of the same HA and/or NA subtype. True heterosubtypic protection, in contrast, appears to be minimal in natural influenza virus hosts. We discuss our findings in the light of the zoonotic and pandemic risks of SIVs.

Dynamic gene expression analysis in a H1N1 influenza virus mouse pneumonia model.

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Bao, Yanyan; Gao, Yingjie; Shi, Yujing; Cui, Xiaolan

2017-06-01

H1N1, a major pathogenic subtype of influenza A virus, causes a respiratory infection in humans and livestock that can range from a mild infection to more severe pneumonia associated with acute respiratory distress syndrome. Understanding the dynamic changes in the genome and the related functional changes induced by H1N1 influenza virus infection is essential to elucidating the pathogenesis of this virus and thereby determining strategies to prevent future outbreaks. In this study, we filtered the significantly expressed genes in mouse pneumonia using mRNA microarray analysis. Using STC analysis, seven significant gene clusters were revealed, and using STC-GO analysis, we explored the significant functions of these seven gene clusters. The results revealed GOs related to H1N1 virus-induced inflammatory and immune functions, including innate immune response, inflammatory response, specific immune response, and cellular response to interferon-beta. Furthermore, the dynamic regulation relationships of the key genes in mouse pneumonia were revealed by dynamic gene network analysis, and the most important genes were filtered, including Dhx58, Cxcl10, Cxcl11, Zbp1, Ifit1, Ifih1, Trim25, Mx2, Oas2, Cd274, Irgm1, and Irf7. These results suggested that during mouse pneumonia, changes in the expression of gene clusters and the complex interactions among genes lead to significant changes in function. Dynamic gene expression analysis revealed key genes that performed important functions. These results are a prelude to advancements in mouse H1N1 influenza virus infection biology, as well as the use of mice as a model organism for human H1N1 influenza virus infection studies.

Altered response to A(H1N1)pnd09 vaccination in pregnant women

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Bischoff, Anne Louise; Følsgaard, Nilofar Vahman; Carson, Charlotte Giwercman

2013-01-01

BACKGROUND: Pregnant women were suspected to be at particular risk when H1N1pnd09 influenza became pandemic in 2009. Our primary objective was to compare the immune responses conferred by MF59®-adjuvanted vaccine (Focetria®) in H1N1pnd09-naïve pregnant and non-pregnant women. The secondary aims...... were to compare influences of dose and adjuvant on the immune response. METHODS: The study was nested in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010) pregnancy cohort in 2009-2010 and conducted as a single-blinded block-randomised [1∶1∶1] controlled clinical trial in pregnant...... women after gestational week 20: (1) 7.5 µg H1N1pnd09 antigen with MF59-adjuvant (Pa7.5 µg); (2) 3.75 µg antigen half MF59-adjuvanted (Pa3.75 µg); (3) 15 µg antigen unadjuvanted (P15 µg); and in non-pregnant women receiving (4) 7.5 µg antigen full adjuvanted (NPa7.5 µg). Blood samples were collected...

Evaluating the most effective distribution strategies to assure administration of pandemic H1N1 influenza vaccine to New York State children and adolescents: evaluation using the New York State Immunization Information System.

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Bednarczyk, Robert A; DuVall, Sarah; Meldrum, Megan D; Flynn, Michael K; Santilli, Loretta A; Easton, Delia E; Sharma, Priya; Blog, Debra S; Zansky, Shelley M; McNutt, Louise-Anne; Birkhead, Guthrie S

2013-01-01

To examine differences in H1N1 influenza vaccine distribution strategies that may impact the ability to rapidly administer vaccine during a pandemic or public health emergency. Retrospective evaluation of immunization data in the New York State Immunization Information System (NYSIIS). Analysis of existing NYSIIS data. Children and adolescents younger than 19 years for whom information on at least 1 H1N1 influenza vaccine was present in NYSIIS. Median time to administer vaccines to children and adolescents younger than 19 years by December 31, 2009, by county; venue of H1N1 vaccine administration (local health department [LHD] or private medical provider); comparison of immunization-seeking behavior for routine childhood vaccinations and H1N1 vaccine. A total of 459 189 first or only doses of H1N1 influenza vaccine were recorded in NYSIIS as being administered to New York State, outside of New York City, children aged less than 19 years, between October 2, 2009, and December 31, 2009. Overall, LHD administered 31% of H1N1 vaccine doses; in counties having population less than 100,000, LHD administered 63% of H1N1 doses compared with 23% in counties having population more than 100,000. Time to median administration was faster for LHD in smaller counties and similar for LHD and private medical providers in larger counties. Children who always received routine childhood immunizations either within or outside of their county of residence often had the same practice for H1N1 vaccine, with 85% of children following these patterns. Children who did not follow these patterns were more likely to receive H1N1 influenza vaccine through LHD. Local health departments were able to rapidly administer large quantities of H1N1 influenza vaccine, and patterns of health care seeking relying on increased use of LHD needs to be further studied for future public health emergency planning.

Airway Mucosal Immune-suppression in Neonates of Mothers Receiving A(H1N1)pnd09 Vaccination During Pregnancy

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Pedersen, Susanne Brix; Bischoff, Anne L.; Folsgaard, Nilofar V.

2015-01-01

, IL-5, IL-13, eotaxin-1, eotaxin-3, TARC, MDC, IL-17, IL-1 beta, IL-8, transforming growth factor beta (TGF)-beta 1, IL-10 and IL-2. Infections were monitored the first year of life by daily diary cards and clinical controls. Results: Neonates of mothers vaccinated during pregnancy had significant up...... significant and positive association to up-regulation of TGF-beta 1 levels (P = 0.0003) and significant negative association to other mediators. The study was not powered to study differences in the incidence of infections in early infancy which did not differ between the study groups. Conclusion: Influenza A......(H1N1) pnd09 vaccination during pregnancy up-regulates TGF-beta 1 and down-regulates key mediators of the protective immunity....

In Silico Identification of Highly Conserved Epitopes of Influenza A H1N1, H2N2, H3N2, and H5N1 with Diagnostic and Vaccination Potential

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José Esteban Muñoz-Medina

2015-01-01

Full Text Available The unpredictable, evolutionary nature of the influenza A virus (IAV is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. In this study, we completed an in silico analysis of the reported epitopes of the 4 IAV proteins that are antigenically most significant (HA, NA, NP, and M2 in the 3 strains with the greatest world circulation in the last century (H1N1, H2N2, and H3N2 and in one of the main aviary subtypes responsible for zoonosis (H5N1. For this purpose, the HMMER program was used to align 3,016 epitopes reported in the Immune Epitope Database and Analysis Resource (IEDB and distributed in 34,294 stored sequences in the Pfam database. Eighteen epitopes were identified: 8 in HA, 5 in NA, 3 in NP, and 2 in M2. These epitopes have remained constant since they were first identified (~91 years and are present in strains that have circulated on 5 continents. These sites could be targets for vaccination design strategies based on epitopes and/or as markers in the implementation of diagnostic techniques.

Replication, Pathogenesis and Transmission of Pandemic (H1N1) 2009 Virus in Non-Immune Pigs

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Brookes, Sharon M; Nunez, Alejandor; Choudhury, Bhudipa

2010-01-01

The declaration of the human influenza A pandemic (H1N1) 2009 (H1N1/09) raised important questions, including origin and host range [1,2]. Two of the three pandemics in the last century resulted in the spread of virus to pigs (H1N1, 1918; H3N2, 1968) with subsequent independent establishment...... and evolution within swine worldwide [3]. A key public and veterinary health consideration in the context of the evolving pandemic is whether the H1N1/09 virus could become established in pig populations [4]. We performed an infection and transmission study in pigs with A/California/07/09. In combination......, with clearly demonstrable pulmonary pathology, there was apparent selection of a virus variant with glycine (225G). These findings provide potential clues to the existence and biological significance of viral receptor-binding variants with 225D and 225G during the 1918 pandemic [5]....

Signal Immune Reactions of Macrophages Differentiated from THP-1 Monocytes to Infection with Pandemic H1N1PDM09 Virus and H5N2 and H9N2 Avian Influenza A Virus.

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Sokolova, T M; Poloskov, V V; Shuvalov, A N; Rudneva, I A; Timofeeva, T A

2018-03-01

In culture of THP-1 cells differentiated into macrophages with PMA (THP-PMA macrophages) infected with influenza viruses of subtypes H1, H5 and H9, we measured the expression of TLR7 and RIG1 receptor genes, sensors of viral RNA and ribonucleoprotein, and the levels of production of inflammatory cytokines IL-1β, TNFα, IL-10, and IFNα. The sensitivity and inflammatory response of THP-PMA macrophages to pandemic influenza A virus H1N1pdm09 and avian influenza H5N2 and H9N2 viruses correlate with the intracellular level of their viral RNA and activation of the RIG1 gene. Abortive infection is accompanied by intensive macrophage secretion of TNFα, IL-1β, and toxic factors inducing cell death. Activity of endosomal TLR7 receptor gene changed insignificantly in 24 h after infection and significantly decreased in 48 and 72 h under the action of H5N2 and H9N2, which correlated with manifestation of the cytopathogenic effect of these viruses. H5N2 and H9N2 avian viruses in THP-PMA macrophages are strong activators of the expression of the gene of the cytoplasmic RIG1 receptor 24 and 48 h after infection, and the pandemic virus H1N1pdm09 is a weak stimulator of RIG1 gene. Avian influenza H5N2 and H9N2 viruses are released by rapid induction of the inflammatory response in macrophages. At the late stages of infection, we observed a minor increase in IL-10 secretion in macrophages and, probably, the polarization of a part of the population in type M2. The studied influenza A viruses are weak inductors of IFN in THP-PMA macrophages. In the culture medium of THP-PMA macrophages infected with H9N2 and H5N2 viruses, MTT test revealed high levels of toxic factors causing the death of Caco-2 cells. In contrast to avian viruses, pandemic virus H1N1pdm09 did not induce production of toxic factors.

Influenza A H5N1 and HIV co-infection: case report

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Simmons Cameron

2010-06-01

Full Text Available Abstract Background The role of adaptive immunity in severe influenza is poorly understood. The occurrence of influenza A/H5N1 in a patient with HIV provided a rare opportunity to investigate this. Case Presentation A 30-year-old male was admitted on day 4 of influenza-like-illness with tachycardia, tachypnea, hypoxemia and bilateral pulmonary infiltrates. Influenza A/H5N1 and HIV tests were positive and the patient was treated with Oseltamivir and broad-spectrum antibiotics. Initially his condition improved coinciding with virus clearance by day 6. He clinically deteriorated as of day 10 with fever recrudescence and increasing neutrophil counts and died on day 16. His admission CD4 count was 100/μl and decreased until virus was cleared. CD8 T cells shifted to a CD27+CD28- phenotype. Plasma chemokine and cytokine levels were similar to those found previously in fatal H5N1. Conclusions The course of H5N1 infection was not notably different from other cases. Virus was cleared despite profound CD4 T cell depletion and aberrant CD8 T cell activation but this may have increased susceptibility to a fatal secondary infection.

Evidence of cross-reactive immunity to 2009 pandemic influenza A virus in workers seropositive to swine H1N1 influenza viruses circulating in Italy.

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Maria A De Marco

Full Text Available BACKGROUND: Pigs play a key epidemiologic role in the ecology of influenza A viruses (IAVs emerging from animal hosts and transmitted to humans. Between 2008 and 2010, we investigated the health risk of occupational exposure to swine influenza viruses (SIVs in Italy, during the emergence and spread of the 2009 H1N1 pandemic (H1N1pdm virus. METHODOLOGY/PRINCIPAL FINDINGS: Serum samples from 123 swine workers (SWs and 379 control subjects (Cs, not exposed to pig herds, were tested by haemagglutination inhibition (HI assay against selected SIVs belonging to H1N1 (swH1N1, H1N2 (swH1N2 and H3N2 (swH3N2 subtypes circulating in the study area. Potential cross-reactivity between swine and human IAVs was evaluated by testing sera against recent, pandemic and seasonal, human influenza viruses (H1N1 and H3N2 antigenic subtypes. Samples tested against swH1N1 and H1N1pdm viruses were categorized into sera collected before (n. 84 SWs; n. 234 Cs and after (n. 39 SWs; n. 145 Cs the pandemic peak. HI-antibody titers ≥10 were considered positive. In both pre-pandemic and post-pandemic peak subperiods, SWs showed significantly higher swH1N1 seroprevalences when compared with Cs (52.4% vs. 4.7% and 59% vs. 9.7%, respectively. Comparable HI results were obtained against H1N1pdm antigen (58.3% vs. 7.7% and 59% vs. 31.7%, respectively. No differences were found between HI seroreactivity detected in SWs and Cs against swH1N2 (33.3% vs. 40.4% and swH3N2 (51.2 vs. 55.4% viruses. These findings indicate the occurrence of swH1N1 transmission from pigs to Italian SWs. CONCLUSION/SIGNIFICANCE: A significant increase of H1N1pdm seroprevalences occurred in the post-pandemic peak subperiod in the Cs (p<0.001 whereas SWs showed no differences between the two subperiods, suggesting a possible occurrence of cross-protective immunity related to previous swH1N1 infections. These data underline the importance of risk assessment and occupational health surveillance activities aimed

Clinical and Immune Responses to Inactivated Influenza A(H1N1)pdm09 Vaccine in Children

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Kotloff, Karen L.; Halasa, Natasha B.; Harrison, Christopher J.; Englund, Janet A.; Walter, Emmanuel B.; King, James C.; Creech, C. Buddy; Healy, Sara A.; Dolor, Rowena J.; Stephens, Ina; Edwards, Kathryn M.; Noah, Diana L.; Hill, Heather; Wolff, Mark

2014-01-01

Background As the influenza AH1N1 pandemic emerged in 2009, children were found to experience high morbidity and mortality and were prioritized for vaccination. This multicenter, randomized, double-blind, age-stratified trial assessed the safety and immunogenicity of inactivated influenza A(H1N1)pdm09 vaccine in healthy children aged 6 months to 17 years. Methods Children received two doses of approximately 15 μg or 30 μg hemagglutin antigen 21 days apart. Reactogenicity was assessed for 8 days after each dose, adverse events through day 42, and serious adverse events or new-onset chronic illnesses through day 201. Serum hemagglutination inhibition (HAI) titers were measured on days 0 (pre-vaccination), 8, 21, 29, and 42. Results A total of 583 children received the first dose and 571 received the second dose of vaccine. Vaccinations were generally well-tolerated and no related serious adverse events were observed. The 15 μg dosage elicited a seroprotective HAI (≥1:40) in 20%, 47%, and 93% of children in the 6-35 month, 3-9 year, and 10-17 year age strata 21 days after dose 1 and in 78%, 82%, and 98% of children 21 days after dose 2, respectively. The 30 μg vaccine dosage induced similar responses. Conclusions The inactivated influenza A(H1N1)pdm09 vaccine exhibited a favorable safety profile at both dosage levels. While a single 15 or 30 μg dose induced seroprotective antibody responses in most 10-17 year olds, younger children required 2 doses, even when receiving dosages 4-6 fold higher than recommended. Well-tolerated vaccines are needed that induce immunity after a single dose for use in young children during influenza pandemics. PMID:25222307

Recombinant Parainfluenza Virus 5 Expressing Hemagglutinin of Influenza A Virus H5N1 Protected Mice against Lethal Highly Pathogenic Avian Influenza Virus H5N1 Challenge

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Li, Zhuo; Mooney, Alaina J.; Gabbard, Jon D.; Gao, Xiudan; Xu, Pei; Place, Ryan J.; Hogan, Robert J.; Tompkins, S. Mark

2013-01-01

A safe and effective vaccine is the best way to prevent large-scale highly pathogenic avian influenza virus (HPAI) H5N1 outbreaks in the human population. The current FDA-approved H5N1 vaccine has serious limitations. A more efficacious H5N1 vaccine is urgently needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, is not known to cause any illness in humans. PIV5 is an attractive vaccine vector. In our studies, a single dose of a live recombinant PIV5 expressing a hemagglutinin (HA) gene of H5N1 (rPIV5-H5) from the H5N1 subtype provided sterilizing immunity against lethal doses of HPAI H5N1 infection in mice. Furthermore, we have examined the effect of insertion of H5N1 HA at different locations within the PIV5 genome on the efficacy of a PIV5-based vaccine. Interestingly, insertion of H5N1 HA between the leader sequence, the de facto promoter of PIV5, and the first viral gene, nucleoprotein (NP), did not lead to a viable virus. Insertion of H5N1 HA between NP and the next gene, V/phosphorprotein (V/P), led to a virus that was defective in growth. We have found that insertion of H5N1 HA at the junction between the small hydrophobic (SH) gene and the hemagglutinin-neuraminidase (HN) gene gave the best immunity against HPAI H5N1 challenge: a dose as low as 1,000 PFU was sufficient to protect against lethal HPAI H5N1 challenge in mice. The work suggests that recombinant PIV5 expressing H5N1 HA has great potential as an HPAI H5N1 vaccine. PMID:23077314

Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses.

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Lyoo, Kwang-Soo; Kim, Jeong-Ki; Jung, Kwonil; Kang, Bo-Kyu; Song, Daesub

2014-09-24

The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decreased. Both the H1N1 and H1N2 infected pigs lacked gross lesions at PID 2, but they showed moderate to severe pneumonia on PID 4, 7 and 14. The pigs infected with H1N1 had significant scores of gross and histopathological lesions when compared with the other pigs infected with H1N2, H3N2, and mock at PID 14. Mean SIV antigen-positive scores were rarely detected for pigs infected with H1N2 and H3N2 from PID 7, whereas a significantly increased amount of viral antigens were found in the bronchioles and alveolar epithelium of the H1N1infected pigs at PID 14. We demonstrated that Korean SIV subtypes had different pulmonary pathologic patterns. The Korean H3N2 rapidly induced acute lung lesions such as broncho-interstitial pneumonia, while the Korean H1N1 showed longer course of infection as compared to other strains.

Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses

OpenAIRE

Lyoo, Kwang-Soo; Kim, Jeong-Ki; Jung, Kwonil; Kang, Bo-Kyu; Song, Daesub

2014-01-01

Background The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. Findings The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decrease...

The seroprevalence of pandemic influenza H1N1 (2009 virus in China.

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Cuiling Xu

2011-04-01

Full Text Available Mainland China experienced pandemic influenza H1N1 (2009 virus (pH1N1 with peak activity during November-December 2009. To understand the geographic extent, risk factors, and attack rate of pH1N1 infection in China we conducted a nationwide serological survey to determine the prevalence of antibodies to pH1N1.Stored serum samples (n = 2,379 collected during 2006-2008 were used to estimate baseline serum reactogenicity to pH1N1. In January 2010, we used a multistage-stratified random sampling method to select 50,111 subjects who met eligibility criteria and collected serum samples and administered a standardized questionnaire. Antibody response to pH1N1 was measured using haemagglutination inhibition (HI assay and the weighted seroprevalence was calculated using the Taylor series linearization method. Multivariable logistic regression analyses were used to examine risk factors for pH1N1 seropositivity. Baseline seroprevalence of pH1N1 antibody (HI titer ≥40 was 1.2%. The weighted seroprevalence of pH1N1 among the Chinese population was 21.5%(vaccinated: 62.0%; unvaccinated: 17.1%. Among unvaccinated participants, those aged 6-15 years (32.9% and 16-24 years (30.3% had higher seroprevalence compared with participants aged 25-59 years (10.7% and ≥60 years (9.9%, P<0.0001. Children in kindergarten and students had higher odds of seropositivity than children in family care (OR: 1.36 and 2.05, respectively. We estimated that 207.7 million individuals (15.9% experienced pH1N1 infection in China.The Chinese population had low pre-existing immunity to pH1N1 and experienced a relatively high attack rate in 2009 of this virus. We recommend routine control measures such as vaccination to reduce transmission and spread of seasonal and pandemic influenza viruses.

Protection from the 2009 H1N1 pandemic influenza by an antibody from combinatorial survivor-based libraries.

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Arun K Kashyap

2010-07-01

Full Text Available Influenza viruses elude immune responses and antiviral chemotherapeutics through genetic drift and reassortment. As a result, the development of new strategies that attack a highly conserved viral function to prevent and/or treat influenza infection is being pursued. Such novel broadly acting antiviral therapies would be less susceptible to virus escape and provide a long lasting solution to the evolving virus challenge. Here we report the in vitro and in vivo activity of a human monoclonal antibody (A06 against two isolates of the 2009 H1N1 pandemic influenza virus. This antibody, which was obtained from a combinatorial library derived from a survivor of highly pathogenic H5N1 infection, neutralizes H5N1, seasonal H1N1 and 2009 "Swine" H1N1 pandemic influenza in vitro with similar potency and is capable of preventing and treating 2009 H1N1 influenza infection in murine models of disease. These results demonstrate broad activity of the A06 antibody and its utility as an anti-influenza treatment option, even against newly evolved influenza strains to which there is limited immunity in the general population.

Hemagglutinin-based polyanhydride nanovaccines against H5N1 influenza elicit protective virus neutralizing titers and cell-mediated immunity

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Ross KA

2014-12-01

Full Text Available Kathleen A Ross,1 Hyelee Loyd,2 Wuwei Wu,2 Lucas Huntimer,3 Shaheen Ahmed,4 Anthony Sambol,5 Scott Broderick,6 Zachary Flickinger,2 Krishna Rajan,6 Tatiana Bronich,4 Surya Mallapragada,1 Michael J Wannemuehler,3 Susan Carpenter,2 Balaji Narasimhan1 1Chemical and Biological Engineering, Iowa State University, Ames, IA, USA; 2Animal Science, Iowa State University, Ames, IA, USA; 3Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA; 4Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA; 5Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA; 6Materials Science and Engineering, Iowa State University, Ames, IA, USA Abstract: H5N1 avian influenza is a significant global concern with the potential to become the next pandemic threat. Recombinant subunit vaccines are an attractive alternative for pandemic vaccines compared to traditional vaccine technologies. In particular, polyanhydride nanoparticles encapsulating subunit proteins have been shown to enhance humoral and cell-mediated immunity and provide protection upon lethal challenge. In this work, a recombinant H5 hemagglutinin trimer (H53 was produced and encapsulated into polyanhydride nanoparticles. The studies performed indicated that the recombinant H53 antigen was a robust immunogen. Immunizing mice with H53 encapsulated into polyanhydride nanoparticles induced high neutralizing antibody titers and enhanced CD4+ T cell recall responses in mice. Finally, the H53-based polyanhydride nanovaccine induced protective immunity against a low-pathogenic H5N1 viral challenge. Informatics analyses indicated that mice receiving the nanovaccine formulations and subsequently challenged with virus were similar to naïve mice that were not challenged. The current studies provide a basis to further exploit the advantages of polyanhydride nanovaccines in pandemic scenarios. Keywords: polymer, nanoparticle, vaccine, subunit

H1N1 influenza (Swine flu)

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Swine flu; H1N1 type A influenza ... The H1N1 virus is now considered a regular flu virus. It is one of the three viruses included in the regular (seasonal) flu vaccine . You cannot get H1N1 flu virus from ...

Distinct T and NK cell populations may serve as immune correlates of protection against symptomatic pandemic influenza A(H1N1 virus infection during pregnancy.

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Miloje Savic

Full Text Available Maternal influenza infection during pregnancy is associated with increased risk of morbidity and mortality. However, the link between the anti-influenza immune responses and health-related risks during infection is not well understood. We have analyzed memory T and NK cell mediated immunity (CMI responses in pandemic influenza A(H1N1pdm09 (pdm09 virus infected non-vaccinated pregnant women participating in the Norwegian Influenza Pregnancy Cohort (NorFlu. The cohort includes information on immunization, self-reported health and disease status, and biological samples (plasma and PBMC. Infected cases (N = 75 were defined by having a serum hemagglutination inhibition (HI titer > = 20 to influenza pdm09 virus at the time of delivery, while controls (N = 75 were randomly selected among non-infected pregnant women (HI titer <10. In ELISpot assays cases had higher frequencies of IFNγ+ CD8+ T cells responding to pdm09 virus or conserved CD8 T cell-restricted influenza A virus epitopes, compared to controls. Within this T cell population, frequencies of CD95+ late effector (CD45RA+CCR7- and naive (CD45RA+CCR7+ CD8+ memory T cells correlated inversely with self-reported influenza illness (ILI symptoms. ILI symptoms in infected women were also associated with lower numbers of poly-functional (IFNγ+TNFα+, IL2+IFNγ+, IL2+IFNγ+TNFα+ CD4+ T cells and increased frequencies of IFNγ+CD3-CD7+ NK cells compared to asymptomatic cases, or controls, after stimulation with the pdm09 virus. Taken together, virus specific and functionally distinct T and NK cell populations may serve as cellular immune correlates of clinical outcomes of pandemic influenza disease in pregnant women. Our results may provide information important for future universal influenza vaccine design.

Distinct T and NK cell populations may serve as immune correlates of protection against symptomatic pandemic influenza A(H1N1) virus infection during pregnancy.

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Savic, Miloje; Dembinski, Jennifer L; Laake, Ida; Hungnes, Olav; Cox, Rebecca; Oftung, Fredrik; Trogstad, Lill; Mjaaland, Siri

2017-01-01

Maternal influenza infection during pregnancy is associated with increased risk of morbidity and mortality. However, the link between the anti-influenza immune responses and health-related risks during infection is not well understood. We have analyzed memory T and NK cell mediated immunity (CMI) responses in pandemic influenza A(H1N1)pdm09 (pdm09) virus infected non-vaccinated pregnant women participating in the Norwegian Influenza Pregnancy Cohort (NorFlu). The cohort includes information on immunization, self-reported health and disease status, and biological samples (plasma and PBMC). Infected cases (N = 75) were defined by having a serum hemagglutination inhibition (HI) titer > = 20 to influenza pdm09 virus at the time of delivery, while controls (N = 75) were randomly selected among non-infected pregnant women (HI titer <10). In ELISpot assays cases had higher frequencies of IFNγ+ CD8+ T cells responding to pdm09 virus or conserved CD8 T cell-restricted influenza A virus epitopes, compared to controls. Within this T cell population, frequencies of CD95+ late effector (CD45RA+CCR7-) and naive (CD45RA+CCR7+) CD8+ memory T cells correlated inversely with self-reported influenza illness (ILI) symptoms. ILI symptoms in infected women were also associated with lower numbers of poly-functional (IFNγ+TNFα+, IL2+IFNγ+, IL2+IFNγ+TNFα+) CD4+ T cells and increased frequencies of IFNγ+CD3-CD7+ NK cells compared to asymptomatic cases, or controls, after stimulation with the pdm09 virus. Taken together, virus specific and functionally distinct T and NK cell populations may serve as cellular immune correlates of clinical outcomes of pandemic influenza disease in pregnant women. Our results may provide information important for future universal influenza vaccine design.

Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.

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Gohil, Devanshi; Kothari, Sweta; Shinde, Pramod; Meharunkar, Rhuta; Warke, Rajas; Chowdhary, Abhay; Deshmukh, Ranjana

2017-08-01

Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country. Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations. The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period. Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation. Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains. Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites. Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion. Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually. The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.

Immune influence of pregnancy on human H7N9 infection: a case report

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G. Cui

2015-05-01

Full Text Available Introduction: H7N9 infection has raised serious concerns worldwide. Pregnant women were considered to be at a high risk of influenza infection. Normal pregnancy was dependent on T helper (Th 2 deviation. However, whether pregnancy influences the immune status of influenza H7N9 patients has not been reported. Case report: Here, we reported a case of pregnant woman in the first trimester with H7N9 infection compared with the two non-pregnant female H7N9 patients for clinical features and relevant immunological changes. We found that there were no differences in plasma levels of Th1 and Th2 cytokines between the pregnant and non-pregnant patients, and there was no Th2 deviation in the acute phase. However, the Th2 deviation was recurrent along with the clearance of infection in the H7N9 pregnant patient. Conclusion: These cases highlighted that the pregnant patient infected with H7N9 could induce an effective Th1 immune response equal to that of non-pregnant patients with H7N9 virus infection, although the pregnancy itself could lead to a Th2 deviation. These data suggested that pregnant patients could acquire a similar antiviral response for H7N9 infection versus non-pregnant patients. Keywords: Influenza, H7N9, Pregnancy, Immunologic characteristics, Cytokines

Potency of whole virus particle and split virion vaccines using dissolving microneedle against challenges of H1N1 and H5N1 influenza viruses in mice.

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Nakatsukasa, Akihiro; Kuruma, Koji; Okamatsu, Masatoshi; Hiono, Takahiro; Suzuki, Mizuho; Matsuno, Keita; Kida, Hiroshi; Oyamada, Takayoshi; Sakoda, Yoshihiro

2017-05-15

Transdermal vaccination using a microneedle (MN) confers enhanced immunity compared with subcutaneous (SC) vaccination. Here we developed a novel dissolving MN patch for the influenza vaccine. The potencies of split virion and whole virus particle (WVP) vaccines prepared from A/Puerto Rico/8/1934 (H1N1) and A/duck/Hokkaido/Vac-3/2007 (H5N1), respectively, were evaluated. MN vaccination induced higher neutralizing antibody responses than SC vaccination in mice. Moreover, MN vaccination with a lower dose of antigens conferred protective immunity against lethal challenges of influenza viruses than SC vaccination in mice. These results suggest that the WVP vaccines administered using MN are an effective combination for influenza vaccine to be further validated in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antigenic variation of H1N1, H1N2 and H3N2 swine influenza viruses in Japan and Vietnam.

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Takemae, Nobuhiro; Nguyen, Tung; Ngo, Long Thanh; Hiromoto, Yasuaki; Uchida, Yuko; Pham, Vu Phong; Kageyama, Tsutomu; Kasuo, Shizuko; Shimada, Shinichi; Yamashita, Yasutaka; Goto, Kaoru; Kubo, Hideyuki; Le, Vu Tri; Van Vo, Hung; Do, Hoa Thi; Nguyen, Dang Hoang; Hayashi, Tsuyoshi; Matsuu, Aya; Saito, Takehiko

2013-04-01

The antigenicity of the influenza A virus hemagglutinin is responsible for vaccine efficacy in protecting pigs against swine influenza virus (SIV) infection. However, the antigenicity of SIV strains currently circulating in Japan and Vietnam has not been well characterized. We examined the antigenicity of classical H1 SIVs, pandemic A(H1N1)2009 (A(H1N1)pdm09) viruses, and seasonal human-lineage SIVs isolated in Japan and Vietnam. A hemagglutination inhibition (HI) assay was used to determine antigenic differences that differentiate the recent Japanese H1N2 and H3N2 SIVs from the H1N1 and H3N2 domestic vaccine strains. Minor antigenic variation between pig A(H1N1)pdm09 viruses was evident by HI assay using 13 mAbs raised against homologous virus. A Vietnamese H1N2 SIV, whose H1 gene originated from a human strain in the mid-2000s, reacted poorly with post-infection ferret serum against human vaccine strains from 2000-2010. These results provide useful information for selection of optimal strains for SIV vaccine production.

Differential host determinants contribute to the pathogenesis of 2009 pandemic H1N1 and human H5N1 influenza A viruses in experimental mouse models.

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Otte, Anna; Sauter, Martina; Alleva, Lisa; Baumgarte, Sigrid; Klingel, Karin; Gabriel, Gülsah

2011-07-01

Influenza viruses are responsible for high morbidities in humans and may, eventually, cause pandemics. Herein, we compared the pathogenesis and host innate immune responses of a seasonal H1N1, two 2009 pandemic H1N1, and a human H5N1 influenza virus in experimental BALB/c and C57BL/6J mouse models. We found that both 2009 pandemic H1N1 isolates studied (A/Hamburg/05/09 and A/Hamburg/NY1580/09) were low pathogenic in BALB/c mice [log mouse lethal dose 50 (MLD(50)) >6 plaque-forming units (PFU)] but displayed remarkable differences in virulence in C57BL/6J mice. A/Hamburg/NY1580/09 was more virulent (logMLD(50) = 3.5 PFU) than A/Hamburg/05/09 (logMLD(50) = 5.2 PFU) in C57BL/6J mice. In contrast, the H5N1 influenza virus was more virulent in BALB/c mice (logMLD(50) = 0.3 PFU) than in C57BL/6J mice (logMLD(50) = 1.8 PFU). Seasonal H1N1 influenza revealed marginal pathogenicity in BALB/c or C57BL/6J mice (logMLD(50) >6 PFU). Enhanced susceptibility of C57BL/6J mice to pandemic H1N1 correlated with a depressed cytokine response. In contrast, enhanced H5N1 virulence in BALB/c mice correlated with an elevated proinflammatory cytokine response. These findings highlight that host determinants responsible for the pathogenesis of 2009 pandemic H1N1 influenza viruses are different from those contributing to H5N1 pathogenesis. Our results show, for the first time to our knowledge, that the C57BL/6J mouse strain is more appropriate for the evaluation and identification of intrinsic pathogenicity markers of 2009 pandemic H1N1 influenza viruses that are "masked" in BALB/c mice. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform.

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Gabitzsch, Elizabeth S; Balint-Junior, Joseph P; Xu, Younong; Balcaitis, Stephanie; Sanders-Beer, Brigitte; Karl, Julie; Weinhold, Kent J; Paessler, Slobodan; Jones, Frank R

2012-11-26

Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (Pnow hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform. Copyright © 2012 Elsevier Ltd. All rights reserved.

Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses

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Sujuan Chen

2017-06-01

Full Text Available H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128 were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14, and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.

Seasonal influenza vaccine and protection against pandemic (H1N1 2009-associated illness among US military personnel.

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Matthew C Johns

Full Text Available INTRODUCTION: A novel A/H1N1 virus is the cause of the present influenza pandemic; vaccination is a key countermeasure, however, few data assessing prior seasonal vaccine effectiveness (VE against the pandemic strain of H1N1 (pH1N1 virus are available. MATERIALS AND METHODS: Surveillance of influenza-related medical encounter data of active duty military service members stationed in the United States during the period of April-October 2009 with comparison of pH1N1-confirmed cases and location and date-matched controls. Crude odds ratios (OR and VE estimates for immunized versus non-immunized were calculated as well as adjusted OR (AOR controlling for sex, age group, and history of prior influenza vaccination. Separate stratified VE analyses by vaccine type (trivalent inactivated [TIV] or live attenuated [LAIV], age groups and hospitalization status were also performed. For the period of April 20 to October 15, 2009, a total of 1,205 cases of pH1N1-confirmed cases were reported, 966 (80% among males and over one-half (58% under 25 years of age. Overall VE for service members was found to be 45% (95% CI, 33 to 55%. Immunization with prior season's TIV (VE = 44%, 95% CI, 32 to 54% as well as LAIV (VE = 24%, 95% CI, 6 to 38% were both found to be associated with protection. Of significance, VE against a severe disease outcome was higher (VE = 62%, 95% CI, 14 to 84% than against milder outcomes (VE = 42%, 95% CI, 29 to 53%. CONCLUSION: A moderate association with protection against clinically apparent, laboratory-confirmed Pandemic (H1N1 2009-associated illness was found for immunization with either TIV or LAIV 2008-09 seasonal influenza vaccines. This association with protection was found to be especially apparent for severe disease as compared to milder outcome, as well as in the youngest and older populations. Prior vaccination with seasonal influenza vaccines in 2004-08 was also independently associated with protection.

1918 pandemic H1N1 DNA vaccine protects ferrets against 2007 H1N1 virus infection

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Bragstad, Karoline; Martel, Cyril Jean-Marie; Aasted, Bent

of the H1N1 pandemic virus from 1918 induce protection in ferrets against infection with a H1N1 (A/New Caledonia/20/99(H1N1)) virus which was included in the conventional vaccine for the 2006-2007 season. The viruses are separated by a time interval of 89 years and differ by 21.2% in the HA1 protein...

Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates.

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Shufang Fan

2009-05-01

Full Text Available The continued spread of highly pathogenic H5N1 influenza viruses among poultry and wild birds, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. Inactivated subvirion or whole-virion H5N1 vaccines have shown promising immunogenicity in clinical trials, but their ability to elicit protective immunity in unprimed human populations remains unknown. A cold-adapted, live attenuated vaccine with the hemagglutinin (HA and neuraminidase (NA genes of an H5N1 virus A/VN/1203/2004 (clade 1 was protective against the pulmonary replication of homologous and heterologous wild-type H5N1 viruses in mice and ferrets. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H5N1 vaccine (AH/AAca that contains HA and NA genes from a recent H5N1 isolate, A/Anhui/2/05 virus (AH/05 (clade 2.3, and the backbone of the cold-adapted influenza H2N2 A/AnnArbor/6/60 virus (AAca. AH/AAca was attenuated in chickens, mice, and monkeys, and it induced robust neutralizing antibody responses as well as HA-specific CD4+ T cell immune responses in rhesus macaques immunized twice intranasally. Importantly, the vaccinated macaques were fully protected from challenge with either the homologous AH/05 virus or a heterologous H5N1 virus, A/bar-headed goose/Qinghai/3/05 (BHG/05; clade 2.2. These results demonstrate for the first time that a cold-adapted H5N1 vaccine can elicit protective immunity against highly pathogenic H5N1 virus infection in a nonhuman primate model and provide a compelling argument for further testing of double immunization with live attenuated H5N1 vaccines in human trials.

Studies on the antibody response of mice and humans after immunization with potential influenza virus A (H1N1) vaccines

International Nuclear Information System (INIS)

Poumbourios, P.; Jackson, D.C.; Oxford, J.S.

1993-01-01

The antibody response of mice and adult humans to immunization with subunit vaccines derived from a pair of antigenically distinct influenza A H1N1 viruses isolate in eggs was investigated. Although the haemagglutinin molecule of each virus differed by only three amino acid residues, highly specific antibody responses were elicited in mice as determined by haemagglutination inhibition and radioimmunoprecipitation assays. Results from competitive radioimmunoassays using monoclonal antibodies of known specificity and a study of the reactivity of mouse antisera with H1N1 field strains indicated that the marked differences in the antibody responses to the two vaccines was due to an amino acid substitution in the distal tip of the haemagglutinin molecule. In contrast, cross reactive antibody responses were elicited in humans presumably due to exposure to viruses related to the candidate vaccine prior to vaccination. Although immunogenic differences are apparent in this pair of antigenically distinct viruses in naive laboratory animals, these differences are not apparent following vaccination of humans that had prior exposure to related viruses. 21 refs., 5 tabs., 4 figs

La influenza A (H1N1: estado actual del conocimiento Influenza A (H1N1 virus: current information

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Laura Margarita González Valdés

2010-03-01

Full Text Available Se revisó la bibliografía actualizada sobre el tema a partir de los principales buscadores, y reuniones internacionales realizadas sobre la pandemia de la influenza A (H1N1. Se tratan los aspectos relacionados con la historia, la aparición de la pandemia, la biología de la enfermedad, la epidemiología, el cuadro clínico, el tratamiento y el pronóstico y la prevención. La gripe A (H1N1 es una pandemia causada por una variante nueva del virus de la Influenza A que ha sufrido cambios antigénicos en la hemaglutinina y la neuraminidasa. Esto hace que la población sea altamente vulnerable a la infección y produce una sobrecarga temporal enorme a los servicios de salud. El virus se trasmite como otros virus Influenza. Su letalidad es similar a la de la influenza estacional, pero puede incrementarse en personas con factores de riesgo y en adultos jóvenes sanos. El asma y el embarazo parecen ser condiciones de base importantes para incrementar la severidad de la infección. Puede existir cierta protección por inmunidad cruzada con cepas que circularon en el pasado. El espectro clínico va desde personas asintomáticas hasta las formas graves que requieren internación en cuidados intensivos, con rápido deterioro hasta llegar a la insuficiencia respiratoria en un plazo de 24 horas. La vacunación durante la pandemia no parece ser suficientemente efectiva. Son necesarios antivirales (oseltamivir y zanamivir, y las medidas preventivas higiénico-sanitarias son muy eficaces.An updated review using the main search motors and international meetings already celebrated related to Influenza A H1N1 pandemics. Items related to the history, the appearance of the pandemics, the biology of the disease, its epidemiology, clinics, treatment, prognosis and prevention. Grippe A H1N1 is a pandemic caused by a new variant of the Influenza A virus that has suffered antigenic changes in haemaglutinin and neuraminidase. This turns populations more susceptible to

Conservation and diversity of influenza A H1N1 HLA-restricted T cell epitope candidates for epitope-based vaccines.

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Paul Thiamjoo Tan

2010-01-01

Full Text Available The immune-related evolution of influenza viruses is exceedingly complex and current vaccines against influenza must be reformulated for each influenza season because of the high degree of antigenic drift among circulating influenza strains. Delay in vaccine production is a serious problem in responding to a pandemic situation, such as that of the current H1N1 strain. Immune escape is generally attributed to reduced antibody recognition of the viral hemagglutinin and neuraminidase proteins whose rate of mutation is much greater than that of the internal non-structural proteins. As a possible alternative, vaccines directed at T cell epitope domains of internal influenza proteins, that are less susceptible to antigenic variation, have been investigated.HLA transgenic mouse strains expressing HLA class I A*0201, A*2402, and B*0702, and class II DRB1*1501, DRB1*0301 and DRB1*0401 were immunized with 196 influenza H1N1 peptides that contained residues of highly conserved proteome sequences of the human H1N1, H3N2, H1N2, H5N1, and avian influenza A strains. Fifty-four (54 peptides that elicited 63 HLA-restricted peptide-specific T cell epitope responses were identified by IFN-gamma ELISpot assay. The 54 peptides were compared to the 2007-2009 human H1N1 sequences for selection of sequences in the design of a new candidate H1N1 vaccine, specifically targeted to highly-conserved HLA-restricted T cell epitopes.Seventeen (17 T cell epitopes in PB1, PB2, and M1 were selected as vaccine targets based on sequence conservation over the past 30 years, high functional avidity, non-identity to human peptides, clustered localization, and promiscuity to multiple HLA alleles. These candidate vaccine antigen sequences may be applicable to any avian or human influenza A virus.

Reassortant H1N1 influenza virus vaccines protect pigs against pandemic H1N1 influenza virus and H1N2 swine influenza virus challenge.

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Yang, Huanliang; Chen, Yan; Shi, Jianzhong; Guo, Jing; Xin, Xiaoguang; Zhang, Jian; Wang, Dayan; Shu, Yuelong; Qiao, Chuanling; Chen, Hualan

2011-09-28

Influenza A (H1N1) virus has caused human influenza outbreaks in a worldwide pandemic since April 2009. Pigs have been found to be susceptible to this influenza virus under experimental and natural conditions, raising concern about their potential role in the pandemic spread of the virus. In this study, we generated a high-growth reassortant virus (SC/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from a novel H1N1 isolate, A/Sichuan/1/2009 (SC/09), and six internal genes from A/Puerto Rico/8/34 (PR8) virus, by genetic reassortment. The immunogenicity and protective efficacy of this reassortant virus were evaluated at different doses in a challenge model using a homologous SC/09 or heterologous A/Swine/Guangdong/1/06(H1N2) virus (GD/06). Two doses of SC/PR8 virus vaccine elicited high-titer serum hemagglutination inhibiting (HI) antibodies specific for the 2009 H1N1 virus and conferred complete protection against challenge with either SC/09 or GD/06 virus, with reduced lung lesions and viral shedding in vaccine-inoculated animals compared with non-vaccinated control animals. These results indicated for the first time that a high-growth SC/PR8 reassortant H1N1 virus exhibits properties that are desirable to be a promising vaccine candidate for use in swine in the event of a pandemic H1N1 influenza. Copyright © 2011 Elsevier B.V. All rights reserved.

A study of analysis PB1-F2 protein of Influenza Viruses A/H1N1pdm09, A/ H3N2, and A/H5N1

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Hana Apsari Pawestri

2016-07-01

Full Text Available Abstrak Tujuan. Protein PB1-F2 (polymerase basic 1-frame 2 adalah protein terbaru yang ditemukan pada virus Influenza dan telah terbukti berperan dalam induksi kematian sel dan patogenitas. Tujuan dari tulisan ini adalah untuk menganalisis protein PB1-F2 pada virus Influenza A/H5N1 dan A/H1N1pdm09. Metode. Kami melakukan pencarian data yang relevan yaitu sekuens gen virus Influenza A/H5N1 dan A/H1N1pdm09 dari Gen Bank National Center for Biotechnology Information (NCBI selama tahun 1997-2015. Data yang digunakan adalah data sekuens nukleotida gen PB1 (polymerase basic1 virus influenza A/H5N1 dan A/H1N1pdm09. Kemudian dilakukan analisis alignment untuk mengetahui variasi protein dan mutasi yang berhubungan dengan patogenitas dan virulensi. Hasil. Kami melakukan penelitian terhadap sekuens PB1-F2 sebanyak 3262 influenza A/H5N1 dan 2472 Influenza A/H1N1pdm09. Hasil analisis menunjukkan bahwa semua sekuens A/H5N1 memiliki panjang yang penuh sebanyak 90 asam amino, kecuali influenza pandemi 2009 hanya memiliki panjang 87 asam amino. Kemudian, ditemukan mutasi yang berhubungan dengan virulensi yang ditunjukan dengan perubahan asam amino Asparagin (N menjadi Serin (S. Mutasi tersebut terjadi pada Influenza A/H5N1 sebanyak 8.5% dan Influenza A/H1N1pdm09 sebanyak 0.5%. Kesimpulan. Ditemukan beberapa variasi panjang asam amino dan mutasi penting pada sekuens PB1-F2 dari subtipe yang berbeda yaitu influenza A/H5N1 dan A/H1N1pdm09  yang mengindikasikan seleksi spesifik karena introduksi dan adaptasi terhadap inang yang berbeda. Diperlukan penelitian lanjutan untuk lebih memahami variasi dan kontribusi protein PB1-F2 tersebut terhadap virulensi dan patogenitas virus Influenza. Kata kunci : Patogenesis, Virus Influenza, Protein  PB1-F2 Abstract Aim. Influenza virus PB1-F2 (polymerase basic 1-frame 2 protein is a novel protein previously shown to be involved in cell death induction and pathogenesis. Here we analysis the PB1-F2 protein of Influenza virus A/H

A study of analysis PB1-F2 protein of Influenza Viruses A/H1N1pdm09, A/ H3N2, and A/H5N1

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Hana Apsari Pawestri

2016-07-01

Full Text Available Abstrak Tujuan. Protein PB1-F2 (polymerase basic 1-frame 2 adalah protein terbaru yang ditemukan pada virus Influenza dan telah terbukti berperan dalam induksi kematian sel dan patogenitas. Tujuan dari tulisan ini adalah untuk menganalisis protein PB1-F2 pada virus Influenza A/H5N1 dan A/H1N1pdm09. Metode. Kami melakukan pencarian data yang relevan yaitu sekuens gen virus Influenza A/H5N1 dan A/H1N1pdm09 dari Gen Bank National Center for Biotechnology Information (NCBI selama tahun 1997-2015. Data yang digunakan adalah data sekuens nukleotida gen PB1 (polymerase basic1 virus influenza A/H5N1 dan A/H1N1pdm09. Kemudian dilakukan analisis alignment untuk mengetahui variasi protein dan mutasi yang berhubungan dengan patogenitas dan virulensi. Hasil. Kami melakukan penelitian terhadap sekuens PB1-F2 sebanyak 3262 influenza A/H5N1 dan 2472 Influenza A/H1N1pdm09. Hasil analisis menunjukkan bahwa semua sekuens A/H5N1 memiliki panjang yang penuh sebanyak 90 asam amino, kecuali influenza pandemi 2009 hanya memiliki panjang 87 asam amino. Kemudian, ditemukan mutasi yang berhubungan dengan virulensi yang ditunjukan dengan perubahan asam amino Asparagin (N menjadi Serin (S. Mutasi tersebut terjadi pada Influenza A/H5N1 sebanyak 8.5% dan Influenza A/H1N1pdm09 sebanyak 0.5%. Kesimpulan. Ditemukan beberapa variasi panjang asam amino dan mutasi penting pada sekuens PB1-F2 dari subtipe yang berbeda yaitu influenza A/H5N1 dan A/H1N1pdm09  yang mengindikasikan seleksi spesifik karena introduksi dan adaptasi terhadap inang yang berbeda. Diperlukan penelitian lanjutan untuk lebih memahami variasi dan kontribusi protein PB1-F2 tersebut terhadap virulensi dan patogenitas virus Influenza. Kata kunci : Patogenesis, Virus Influenza, Protein  PB1-F2 Abstract Aim. Influenza virus PB1-F2 (polymerase basic 1-frame 2 protein is a novel protein previously shown to be involved in cell death induction and pathogenesis. Here we analysis the PB1-F2 protein of Influenza virus A/H

2009 H1N1 Flu Vaccine Facts

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... of this page please turn Javascript on. Feature: Flu 2009 H1N1 Flu Vaccine Facts Past Issues / Fall 2009 Table of ... the H1N1 flu vaccine. 1 The 2009 H1N1 flu vaccine is safe and well tested. Clinical trials ...

Genetic divergence of influenza A NS1 gene in pandemic 2009 H1N1 isolates with respect to H1N1 and H3N2 isolates from previous seasonal epidemics

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Campanini Giulia

2010-09-01

Full Text Available Abstract Background The Influenza A pandemic sustained by a new H1N1 variant (H1N1v started in Mexico and the USA at the end of April 2009 spreading worldwide in a few weeks. In this study we investigate the variability of the NS1 gene of the pandemic H1N1v strain with respect to previous seasonal strains circulating in humans and the potential selection of virus variants through isolation in cell culture. Methods During the period April 27th 2009-Jan 15th 2010, 1633 potential 2009 H1N1v cases have been screened at our center using the CDC detection and typing realtime RT-PCR assays. Virus isolation on MDCK cells was systematically performed in 1/10 positive cases. A subset of 51 H1N1v strains isolated in the period May-September 2009 was selected for NS1 gene sequencing. In addition, 15 H1N1 and 47 H3N2 virus isolates from three previous seasonal epidemics (2006-2009 were analyzed in parallel. Results A low variability in the NS1 amino acid (aa sequence among H1N1v isolates was shown (aa identity 99.5%. A slightly higher NS1 variability was observed among H1N1 and H3N2 strains from previous epidemics (aa identity 98.6% and 98.9%, respectively. The H1N1v strains were closely related (aa identity 92.1% to swine reference strain (A/swine/Oklahoma/042169/2008. In contrast, substantial divergence (aa identity 83.4% with respect to human reference strain A/Brevig Mission/1/1918 and previous epidemic strains H1N1 and H3N2 (aa identity 78.9% and 77.6%, respectively was shown. Specific sequence signatures of uncertain significance in the new virus variant were a C-terminus deletion and a T215P substitution. Conclusions The H1N1v NS1 gene was more conserved than that of previous epidemic strains. In addition, a closer genetic identity of H1N1v with the swine than the human reference strains was shown. Hot-spots were shown in the H1N1v NS1 aa sequence whose biologic relevance remains to be investigated.

Acceptance and tolerability of an adjuvanted nH1N1 vaccine in HIV-infected patients in the cologne-bonn cohort

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Steffens B

2011-07-01

Full Text Available Abstract Objective To evaluate the acceptance and tolerability of the nH1N1 2009 vaccine in HIV-positive individuals. Method 758 patients were included in this prospective study. Different study populations were formed: The Tolerability Study Group consists of HIV-infected patients who visited three outpatient clinics (Cologne, Bonn, Freiburg during a predefined time period. Patients were offered nH1N1 vaccination. Those accepting were administered a standard dose AS03 adjuvant nH1N1 vaccine. Questionnaires to report side effects occurring within 7 days after immunization were handed out. In a substudy conducted during the same time period, acceptance towards immunization was recorded. This Acceptance Study Group consists of all HIV-infected patients visiting the Cologne clinic. They were offered vaccination. In case of refusal, motivation was recorded. Results In the Tolerability Study Group, a total of 475 patient diaries returned in the three study centres could be evaluated, 119 of those (25% reported no side effects. Distribution of symptoms was as follows: Pain 285/475 patients (60%, swelling 96 (20%, redness 54 (11%, fever 48/475 (10%, muscle/joint ache 173 (36%, headache 127 (27%, and fatigue 210 (44%. Association of side effects with clinical data was calculated for patients in Cologne and Bonn. Incidence of side effects was significantly associated with CDC stages A, B compared to C, and with a detectable viral load (> 50 copies/mL. No correlation was noted for CD4 cell count, age, gender or ethnicity. In the Acceptance Study Group, 538 HIV-infected patients were offered vaccination, 402 (75% accepted, while 136 (25% rejected. Main reasons for rejection were: Negative media coverage (35%, indecisiveness with preference to wait until a later date (23%, influenza not seen as personal threat (19% and scepticism towards immunization in general (10%. Conclusion A total of 622 HIV-infected patients were vaccinated against nH1N1-influenza in

Seroprevalence of H1N1, H3N2 and H1N2 influenza viruses in pigs in seven European countries in 2002-2003.

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Van Reeth, Kristien; Brown, Ian H; Dürrwald, Ralf; Foni, Emanuela; Labarque, Geoffrey; Lenihan, Patrick; Maldonado, Jaime; Markowska-Daniel, Iwona; Pensaert, Maurice; Pospisil, Zdenek; Koch, Guus

2008-05-01

Avian-like H1N1 and human-like H3N2 swine influenza viruses (SIV) have been considered widespread among pigs in Western Europe since the 1980s, and a novel H1N2 reassortant with a human-like H1 emerged in the mid 1990s. This study, which was part of the EC-funded 'European Surveillance Network for Influenza in Pigs 1', aimed to determine the seroprevalence of the H1N2 virus in different European regions and to compare the relative prevalences of each SIV between regions. Laboratories from Belgium, the Czech Republic, Germany, Italy, Ireland, Poland and Spain participated in an international serosurvey. A total of 4190 sow sera from 651 farms were collected in 2002-2003 and examined in haemagglutination inhibition tests against H1N1, H3N2 and H1N2. In Belgium, Germany, Italy and Spain seroprevalence rates to each of the three SIV subtypes were high (> or =30% of the sows seropositive) to very high (> or =50%), except for a lower H1N2 seroprevalence rate in Italy (13.8%). Most sows in these countries with high pig populations had antibodies to two or three subtypes. In Ireland, the Czech Republic and Poland, where swine farming is less intensive, H1N1 was the dominant subtype (8.0-11.7% seropositives) and H1N2 and H3N2 antibodies were rare (0-4.2% seropositives). Thus, SIV of H1N1, H3N2 and H1N2 subtype are enzootic in swine producing regions of Western Europe. In Central Europe, SIV activity is low and the circulation of H3N2 and H1N2 remains to be confirmed. The evolution and epidemiology of SIV throughout Europe is being further monitored through a second 'European Surveillance Network for Influenza in Pigs'.

Exposure to a low pathogenic A/H7N2 virus in chickens protects against highly pathogenic A/H7N1 virus but not against subsequent infection with A/H5N1.

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Júlia Vergara-Alert

Full Text Available Recent evidences have demonstrated that the presence of low pathogenic avian influenza viruses (LPAIV may play an important role in host ecology and transmission of avian influenza viruses (AIV. While some authors have clearly demonstrated that LPAIV can mutate to render highly pathogenic avian influenza viruses (HPAIV, others have shown that their presence could provide the host with enough immunological memory to resist re-infections with HPAIV. In order to experimentally study the role of pre-existing host immunity, chickens previously infected with H7N2 LPAIV were subsequently challenged with H7N1 HPAIV. Pre-infection of chickens with H7N2 LAPIV conferred protection against the lethal challenge with H7N1 HPAIV, dramatically reducing the viral shedding, the clinical signs and the pathological outcome. Correlating with the protection afforded, sera from chickens primed with H7N2 LPAIV reacted with the H7-AIV subtype in hemagglutination inhibition assay and specifically with the N2-neuraminidase antigen. Conversely, subsequent exposure to H5N1 HPAIV resulted in a two days-delay on the onset of disease but all chickens died by 7 days post-challenge. Lack of protection correlated with the absence of H5-hemagglutining inhibitory antibodies prior to H5N1 HPAIV challenge. Our data suggest that in naturally occurring outbreaks of HPAIV, birds with pre-existing immunity to LPAIV could survive lethal infections with HA-homologous HPAIV but not subsequent re-infections with HA-heterologous HPAIV. These results could be useful to better understand the dynamics of AIV in chickens and might help in future vaccine formulations.

Impact of Body Mass Index on Immunogenicity of Pandemic H1N1 Vaccine in Children and Adults

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Callahan, S. Todd; Wolff, Mark; Hill, Heather R.; Edwards, Kathryn M.; Keitel, Wendy; Atmar, Robert; Patel, Shital; Sahly, Hana El; Munoz, Flor; Paul Glezen, W.; Brady, Rebecca; Frenck, Robert; Bernstein, David; Harrison, Christopher; Jackson, Mary Anne; Swanson, Douglas; Newland, Jason; Myers, Angela; Livingston, Robyn A; Walter, Emmanuel; Dolor, Rowena; Schmader, Kenneth; Mulligan, Mark J.; Edupuganti, Srilatha; Rouphael, Nadine; Whitaker, Jennifer; Spearman, Paul; Keyserling, Harry; Shane, Andi; Eckard, Allison Ross; Jackson, Lisa A.; Frey, Sharon E.; Belshe, Robert B.; Graham, Irene; Anderson, Edwin; Englund, Janet A.; Healy, Sara; Winokur, Patricia; Stapleton, Jack; Meier, Jeffrey; Kotloff, Karen; Chen, Wilbur; Hutter, Julia; Stephens, Ina; Wooten, Susan; Wald, Anna; Johnston, Christine; Edwards, Kathryn M.; Buddy Creech, C.; Todd Callahan, S.

2014-01-01

Obesity emerged as a risk factor for morbidity and mortality related to 2009 pandemic influenza A (H1N1) infection. However, few studies examine the immune responses to H1N1 vaccine among children and adults of various body mass indices (BMI). Pooling data from 3 trials of unadjuvanted split-virus H1N1 A/California/07/2009 influenza vaccines, we analyzed serologic responses of participants stratified by BMI grouping. A single vaccine dose produced higher hemagglutination inhibition antibody titers at day 21 in obese compared to nonobese adults, but there were no significant differences in responses to H1N1 vaccine among children or adults of various BMI following 2 doses. PMID:24795475

Comparative analyses of pandemic H1N1 and seasonal H1N1, H3N2, and influenza B infections depict distinct clinical pictures in ferrets.

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Stephen S H Huang

Full Text Available Influenza A and B infections are a worldwide health concern to both humans and animals. High genetic evolution rates of the influenza virus allow the constant emergence of new strains and cause illness variation. Since human influenza infections are often complicated by secondary factors such as age and underlying medical conditions, strain or subtype specific clinical features are difficult to assess. Here we infected ferrets with 13 currently circulating influenza strains (including strains of pandemic 2009 H1N1 [H1N1pdm] and seasonal A/H1N1, A/H3N2, and B viruses. The clinical parameters were measured daily for 14 days in stable environmental conditions to compare clinical characteristics. We found that H1N1pdm strains had a more severe physiological impact than all season strains where pandemic A/California/07/2009 was the most clinically pathogenic pandemic strain. The most serious illness among seasonal A/H1N1 and A/H3N2 groups was caused by A/Solomon Islands/03/2006 and A/Perth/16/2009, respectively. Among the 13 studied strains, B/Hubei-Wujiagang/158/2009 presented the mildest clinical symptoms. We have also discovered that disease severity (by clinical illness and histopathology correlated with influenza specific antibody response but not viral replication in the upper respiratory tract. H1N1pdm induced the highest and most rapid antibody response followed by seasonal A/H3N2, seasonal A/H1N1 and seasonal influenza B (with B/Hubei-Wujiagang/158/2009 inducing the weakest response. Our study is the first to compare the clinical features of multiple circulating influenza strains in ferrets. These findings will help to characterize the clinical pictures of specific influenza strains as well as give insights into the development and administration of appropriate influenza therapeutics.

1H-1H correlations across N-H···N hydrogen bonds in nucleic acids

International Nuclear Information System (INIS)

Majumdar, Ananya; Gosser, Yuying; Patel, Dinshaw J.

2001-01-01

In 2H J NN -COSY experiments, which correlate protons with donor/acceptor nitrogens across N d ···HN a bonds, the receptor nitrogen needs to be assigned in order to unambiguously identify the hydrogen bond. For many situations this is a non-trivial task which is further complicated by poor dispersion of (N a ,N d ) resonances. To address these problems, we present pulse sequences to obtain direct, internucleotide correlations between protons in uniformly 13 C/ 15 N labeled nucleic acids containing N d ···HN a hydrogen bonds. Specifically, the pulse sequence H2(N1N3)H3 correlates H2(A,ω 1 ):H3(U,ω 2 ) protons across Watson-Crick A-U and mismatched G·A base pairs, the sequences H5(N3N1)H1/H6(N3N1)H1 correlate H5(C,ω 1 )/H6(C,ω 1 ):H1(G,ω 2 ) protons across Watson-Crick G-C base pairs, and the H 2 (N2N7)H8 sequence correlates NH 2 (G,A,C;ω 1 ):H8(G,A;ω 2 ) protons across G·G, A·A, sheared G·A and other mismatch pairs. These 1 H- 1 H connectivities circumvent the need for independent assignment of the donor/acceptor nitrogen and related degeneracy issues associated with poorly dispersed nitrogen resonances. The methodology is demonstrated on uniformly 13 C/ 15 N labeled samples of (a) an RNA regulatory element involving the HIV-1 TAR RNA fragment, (b) a multi-stranded DNA architecture involving a G·(C-A) triad-containing G-quadruplex and (c) a peptide-RNA complex involving an evolved peptide bound to the HIV-1 Rev response element (RRE) RNA fragment

Safety of pandemic H1N1 vaccines in children and adolescents.

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Wijnans, Leonoor; de Bie, Sandra; Dieleman, Jeanne; Bonhoeffer, Jan; Sturkenboom, Miriam

2011-10-06

During the 2009 influenza A (H1N1) pandemic several pandemic H1N1 vaccines were licensed using fast track procedures, with relatively limited data on the safety in children and adolescents. Different extensive safety monitoring efforts were put in place to ensure timely detection of adverse events following immunization. These combined efforts have generated large amounts of data on the safety of the different pandemic H1N1 vaccines, also in children and adolescents. In this overview we shortly summarize the safety experience with seasonal influenza vaccines as a background and focus on the clinical and post marketing safety data of the pandemic H1N1 vaccines in children. We identified 25 different clinical studies including 10,505 children and adolescents, both healthy and with underlying medical conditions, between the ages of 6 months and 23 years. In addition, large monitoring efforts have resulted in large amounts of data, with almost 13,000 individual case reports in children and adolescents to the WHO. However, the diversity in methods and data presentation in clinical study publications and publications of spontaneous reports hampered the analysis of safety of the different vaccines. As a result, relatively little has been learned on the comparative safety of these pandemic H1N1 vaccines - particularly in children. It should be a collective effort to give added value to the enormous work going into the individual studies by adhering to available guidelines for the collection, analysis, and presentation of vaccine safety data in clinical studies and to guidance for the clinical investigation of medicinal products in the pediatric population. Importantly the pandemic has brought us the beginning of an infrastructure for collaborative vaccine safety studies in the EU, USA and globally. Copyright © 2011 Elsevier Ltd. All rights reserved.

Self-reported adverse reactions in 4337 healthcare workers immunizations against novel H1N1 influenza

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Seybold Joachim

2011-08-01

Full Text Available Abstract Purpose The use of the 2009 H1N1 vaccine has generated much debate concerning safety issues among the general population and physicians. It was questioned if this is a safe vaccine. Therefore, we investigated the safety of an inactivated monovalent H1N1 pandemic influenza vaccine Methods We focused on the H1N1 pandemic influenza vaccine Pandemrix® and applied a self reporting questionnaire in a population of healthcare workers (HCWs and medical students at a major university hospital. Results In total, 4337 individuals were vaccinated, consisting of 3808 HCWs and 529 medical students. The vaccination rate of the employees was higher than 40%. The majority of individuals were vaccinated in November 2009. In total, 291 of the 4337 vaccinations were reported to lead to one or more adverse reactions (6.7%. Local reactions were reported in 3.8%, myalgia and arthralgia in 3.7%, fatigue in 3.7%, headache in 3.1%. Conclusions Our data together with available data from several national and international institutions points to a safe pandemic influenza vaccine.

Antigenically Diverse Swine Origin H1N1 Variant Influenza Viruses Exhibit Differential Ferret Pathogenesis and Transmission Phenotypes.

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Pulit-Penaloza, Joanna A; Jones, Joyce; Sun, Xiangjie; Jang, Yunho; Thor, Sharmi; Belser, Jessica A; Zanders, Natosha; Creager, Hannah M; Ridenour, Callie; Wang, Li; Stark, Thomas J; Garten, Rebecca; Chen, Li-Mei; Barnes, John; Tumpey, Terrence M; Wentworth, David E; Maines, Taronna R; Davis, C Todd

2018-06-01

Influenza A(H1) viruses circulating in swine represent an emerging virus threat, as zoonotic infections occur sporadically following exposure to swine. A fatal infection caused by an H1N1 variant (H1N1v) virus was detected in a patient with reported exposure to swine and who presented with pneumonia, respiratory failure, and cardiac arrest. To understand the genetic and phenotypic characteristics of the virus, genome sequence analysis, antigenic characterization, and ferret pathogenesis and transmissibility experiments were performed. Antigenic analysis of the virus isolated from the fatal case, A/Ohio/09/2015, demonstrated significant antigenic drift away from the classical swine H1N1 variant viruses and H1N1 pandemic 2009 viruses. A substitution in the H1 hemagglutinin (G155E) was identified that likely impacted antigenicity, and reverse genetics was employed to understand the molecular mechanism of antibody escape. Reversion of the substitution to 155G, in a reverse genetics A/Ohio/09/2015 virus, showed that this residue was central to the loss of hemagglutination inhibition by ferret antisera raised against a prototypical H1N1 pandemic 2009 virus (A/California/07/2009), as well as gamma lineage classical swine H1N1 viruses, demonstrating the importance of this residue for antibody recognition of this H1 lineage. When analyzed in the ferret model, A/Ohio/09/2015 and another H1N1v virus, A/Iowa/39/2015, as well as A/California/07/2009, replicated efficiently in the respiratory tract of ferrets. The two H1N1v viruses transmitted efficiently among cohoused ferrets, but respiratory droplet transmission studies showed that A/California/07/2009 transmitted through the air more efficiently. Preexisting immunity to A/California/07/2009 did not fully protect ferrets from challenge with A/Ohio/09/2015. IMPORTANCE Human infections with classical swine influenza A(H1N1) viruses that circulate in pigs continue to occur in the United States following exposure to swine. To

Advances and Future Challenges in Recombinant Adenoviral Vectored H5N1 Influenza Vaccines

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Jianfeng Zhang

2012-11-01

Full Text Available The emergence of a highly pathogenic avian influenza virus H5N1 has increased the potential for a new pandemic to occur. This event highlights the necessity for developing a new generation of influenza vaccines to counteract influenza disease. These vaccines must be manufactured for mass immunization of humans in a timely manner. Poultry should be included in this policy, since persistent infected flocks are the major source of avian influenza for human infections. Recombinant adenoviral vectored H5N1 vaccines are an attractive alternative to the currently licensed influenza vaccines. This class of vaccines induces a broadly protective immunity against antigenically distinct H5N1, can be manufactured rapidly, and may allow mass immunization of human and poultry. Recombinant adenoviral vectors derived from both human and non-human adenoviruses are currently being investigated and appear promising both in nonclinical and clinical studies. This review will highlight the current status of various adenoviral vectored H5N1 vaccines and will outline novel approaches for the future.

Upregulation of TGF-beta 1 in neonates of mothers receiving Influenza A (H1N1) vaccination during pregnancy

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Bischoff, Anne Louise; Folsgaard, N.; Bisgaard, H.

2012-01-01

Background: Influenza vaccination of pregnant women is generally considered safe,but the effects on the immune system of the unborn child are unknown.Objectives: Our primary objective was to explore differences in cytokine and chemokine levels in nasal mucosal lining fluid in neonates of mothers...... vaccinated during or after pregnancy. Method: IFN-c, IL-1b, IL-2, -4, -5, -10, - 12p70, -13, -17, TNF-a, IL-8, eotaxin-1,eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1b, TGF-b1 and TARC were quantified in nasal mucosal lining fluid in neonates of mothers receiving Influenza A (H1N1v) vaccine during (n = 52......) or after pregnancy (n = 118) in our unselected Copenhagen Prospective Study on Asthma in Childhood 2010 birth-cohort. Result: Neonates of mothers vaccinated during pregnancy showed a significant up-regulation of the immune-regulatory TGF-b1 (P = 0.0004), significant down regulation (P

Experimental and Field Results Regarding Immunity Induced by a Recombinant Turkey Herpesvirus H5 Vector Vaccine Against H5N1 and Other H5 Highly Pathogenic Avian Influenza Virus Challenges.

Science.gov (United States)

Gardin, Yannick; Palya, Vilmos; Dorsey, Kristi Moore; El-Attrache, John; Bonfante, Francesco; Wit, Sjaak de; Kapczynski, Darrell; Kilany, Walid Hamdy; Rauw, Fabienne; Steensels, Mieke; Soejoedono, Retno D

2016-05-01

Vaccination against H5N1 highly pathogenic avian influenza (AI) virus (HPAIV) is one of the possible complementary means available for affected countries to control AI when the disease has become, or with a high risk of becoming, endemic. Efficacy of the vaccination against AI relies essentially, but not exclusively, on the capacity of the vaccine to induce immunity against the targeted virus (which is prone to undergo antigenic variations), as well as its capacity to overcome interference with maternal immunity transmitted by immunized breeding hens to their progeny. This property of the vaccine is a prerequisite for its administration at the hatchery, which assures higher and more reliable vaccine coverage of the populations than vaccination at the farm. A recombinant vector vaccine (Vectormune® AI), based on turkey herpesvirus expressing the hemagglutinin gene of an H5N1 HPAIV as an insert, has been used in several experiments conducted in different research laboratories, as well as in controlled field trials. The results have demonstrated a high degree of homologous and cross protection against different genetic clades of the H5N1 HPAIV. Furthermore, vaccine-induced immunity was not impaired by the presence of passive immunity, but on the contrary, cumulated with it for improved early protection. The demonstrated levels of protection against the different challenge viruses exhibited variations in terms of postchallenge mortality, as well as challenge virus shedding. The data presented here highlight the advantages of this vaccine as a useful and reliable tool to complement biosecurity and sanitary policies for better controlling the disease due to HPAIV of H5 subtypes, when the vaccination is applied as a control measure.

Risk factors affecting seroconversion after influenza A/H1N1 vaccination in hemodialysis patients

Directory of Open Access Journals (Sweden)

Moon Sung Jin

2012-12-01

Full Text Available Abstracts Background Hemodialysis (HD patients have multiple causes of immune dysfunction and poor immune response to influenza vaccination. We investigated the antibody response rate to a pandemic H1N1/2009 influenza vaccination and clinical parameters influencing the induction of antibody responses in HD patients. Methods A total of 114 HD patients were vaccinated with a monovalent adjuvanted H1N1 inactivated influenza vaccine. Titers of neutralizing antibodies were evaluated by hemagglutination inhibition (HI assay at pre- and 4 weeks after vaccination. Seroconversion was defined as either a pre-vaccination HI titer  1:40 or a pre-vaccination HI titer ≥ 1:10 and a minimum four-fold rise in post-vaccination HI antibody titer. Seventeen out of 114 HD patients (14.9% tested positive for antibodies against influenza A/H1N1/2009 before vaccination. The remaining 97 baseline sero-negative patients were included in the analysis. Results Only 30 (30.9% HD patients had seroconversion 4 weeks after vaccination. The elderly patients, those over 65 years of age, showed significantly lower seroconversion rate compared to younger HD patients (20.5% vs. 39.6%, p = 0.042. Furthermore, patients with hemoglobin values less than 10 g/dL had a significantly lower seroconversion rate compared to those with higher hemoglobin values (20.0 vs. 38.6%, p = 0.049. By multivariate logistic regression analysis, only age ≥65 years (OR = 0.336, 95% confidence interval (CI 0.116-0.971, p = 0.044 and hemoglobin levels Conclusions Our data show that HD patients, especially who are elderly with low hemoglobin levels, are at increased risk for lower seroconversion rate after influenza A/H1N1 vaccination. Further studies are needed to improve the efficacy of vaccination in these high risk patients.

NS Segment of a 1918 Influenza A Virus-Descendent Enhances Replication of H1N1pdm09 and Virus-Induced Cellular Immune Response in Mammalian and Avian Systems

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Petersen, Henning; Mostafa, Ahmed; Tantawy, Mohamed A.; Iqbal, Azeem A.; Hoffmann, Donata; Tallam, Aravind; Selvakumar, Balachandar; Pessler, Frank; Beer, Martin; Rautenschlein, Silke; Pleschka, Stephan

2018-01-01

The 2009 pandemic influenza A virus (IAV) H1N1 strain (H1N1pdm09) has widely spread and is circulating in humans and swine together with other human and avian IAVs. This fact raises the concern that reassortment between H1N1pdm09 and co-circulating viruses might lead to an increase of H1N1pdm09 pathogenicity in different susceptible host species. Herein, we explored the potential of different NS segments to enhance the replication dynamics, pathogenicity and host range of H1N1pdm09 strain A/Giessen/06/09 (Gi-wt). The NS segments were derived from (i) human H1N1- and H3N2 IAVs, (ii) highly pathogenic- (H5- or H7-subtypes) or (iii) low pathogenic avian influenza viruses (H7- or H9-subtypes). A significant increase of growth kinetics in A549 (human lung epithelia) and NPTr (porcine tracheal epithelia) cells was only noticed in vitro for the reassortant Gi-NS-PR8 carrying the NS segment of the 1918-descendent A/Puerto Rico/8/34 (PR8-wt, H1N1), whereas all other reassortants showed either reduced or comparable replication efficiencies. Analysis using ex vivo tracheal organ cultures of turkeys (TOC-Tu), a species susceptible to IAV H1N1 infection, demonstrated increased replication of Gi-NS-PR8 compared to Gi-wt. Also, Gi-NS-PR8 induced a markedly higher expression of immunoregulatory and pro-inflammatory cytokines, chemokines and interferon-stimulated genes in A549 cells, THP-1-derived macrophages (dHTP) and TOC-Tu. In vivo, Gi-NS-PR8 induced an earlier onset of mortality than Gi-wt in mice, whereas, 6-week-old chickens were found to be resistant to both viruses. These data suggest that the specific characteristics of the PR8 NS segments can impact on replication, virus induced cellular immune responses and pathogenicity of the H1N1pdm09 in different avian and mammalian host species. PMID:29623073

Evaluation of twenty rapid antigen tests for the detection of human influenza A H5N1, H3N2, H1N1, and B viruses.

Science.gov (United States)

Taylor, Janette; McPhie, Kenneth; Druce, Julian; Birch, Chris; Dwyer, Dominic E

2009-11-01

Twenty rapid antigen assays were compared for their ability to detect influenza using dilutions of virus culture supernatants from human isolates of influenza A H5N1 (clade 1 and 2 strains), H3N2 and H1N1 viruses, and influenza B. There was variation amongst the rapid antigen assays in their ability to detect different influenza viruses. Six of the 12 assays labeled as distinguishing between influenza A and B had comparable analytical sensitivities for detecting both influenza A H5N1 strains, although their ability to detect influenza A H3N2 and H1N1 strains varied. The two assays claiming H5 specificity did not detect either influenza A H5N1 strains, and the two avian influenza-specific assays detected influenza A H5N1, but missed some influenza A H3N2 virus supernatants. Clinical trials of rapid antigen tests for influenza A H5N1 are limited. For use in a pandemic where novel influenza strains are circulating (such as the current novel influenza A H1N1 09 virus), rapid antigen tests should ideally have comparable sensitivity and specificity for the new strains as for co-circulating seasonal influenza strains.

Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N-linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic.

Science.gov (United States)

Ushirogawa, Hiroshi; Naito, Tadasuke; Tokunaga, Hirotoshi; Tanaka, Toshihiro; Nakano, Takashi; Terada, Kihei; Ohuchi, Masanobu; Saito, Mineki

2016-08-08

Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved by antigenic drift; this evolution has resulted in the acquisition of asparagine (N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA), thereby affecting the antigenic and receptor-binding properties, as well as virulence. An epidemiological survey indicated that although the traditional seasonal H1N1 strain had disappeared, H3N2 became predominant again in the seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009. Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks additional NGSs, clinically isolated H3N2 strains obtained during these seasons gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs. To investigate whether these NGSs are associated with re-emergence of H3N2 within the subtype, we tested the effect of amino acid substitutions on neutralizing activity by using the antisera raised against H3N2 strains with or without additional NGSs. Furthermore, because the N residue at position 144 of HA was identified as the site of mismatch between the vaccine and epidemic strains of 2011-2012, we generated mutant viruses by reverse genetics and tested the functional importance of this particular NGS for antibody-mediated neutralization by intranasal inoculation of mice. The results indicated that amino acid substitution at residue 144 significantly affected neutralization activity, acting as an escape mutation. Our data suggest that the newly acquired NGSs in the HA globular head may play an important role in the re-emergence of endemic seasonal H3N2 strain by aiding the escape from humoral immunity.

Multiplex RT-PCR assay for differentiating European swine influenza virus subtypes H1N1, H1N2 and H3N2.

Science.gov (United States)

Chiapponi, Chiara; Moreno, Ana; Barbieri, Ilaria; Merenda, Marianna; Foni, Emanuela

2012-09-01

In Europe, three major swine influenza viral (SIV) subtypes (H1N1, H1N2 and H3N2) have been isolated in pigs. Developing a test that is able to detect and identify the subtype of the circulating strain rapidly during an outbreak of respiratory disease in the pig population is of essential importance. This study describes two multiplex RT-PCRs which distinguish the haemagglutinin (HA) gene and the neuraminidase (NA) gene of the three major subtypes of SIV circulating in Europe. The HA PCR was able to identify the lineage (avian or human) of the HA of H1 subtypes. The analytical sensitivity of the test, considered to be unique, was assessed using three reference viruses. The detection limit corresponded to 1×10(-1) TCID(50)/200μl for avian-like H1N1, 1×10(0) TCID(50)/200μl for human-like H1N2 and 1×10(1) TCID(50)/200μl for H3N2 SIV. The multiplex RT-PCR was first carried out on a collection of 70 isolated viruses showing 100% specificity and then on clinical samples, from which viruses had previously been isolated, resulting in an 89% positive specificity of the viral subtype. Finally, the test was able to identify the viral subtype correctly in 56% of influenza A positive samples, from which SIV had not been isolated previously. It was also possible to identify mixed viral infections and the circulation of a reassortant strain before performing genomic studies. Copyright © 2012 Elsevier B.V. All rights reserved.

Seroprevalence of H1N1, H3N2 and H1N2 influenza viruses in pigs in seven European countries in 2002-2003

NARCIS (Netherlands)

Reeth, K.; Brown, I.H.; Durrwald, R.; Foni, E.; Labarque, G.; Lenihan, P.; Maldonado, J.; Markowska-Daniel, I.; Pensaert, M.; Pospisil, Z.; Koch, G.

2008-01-01

Objectives Avian-like H1N1 and human-like H3N2 swine influenza viruses (SIV) have been considered widespread among pigs in Western Europe since the 1980s, and a novel H1N2 reassortant with a human-like H1 emerged in the mid 1990s. This study, which was part of the EC-funded 'European Surveillance

Influenza A (H1N1) organising pneumonia.

Science.gov (United States)

Torrego, Alfons; Pajares, Virginia; Mola, Anna; Lerma, Enrique; Franquet, Tomás

2010-04-27

In November 2009, countries around the world reported confirmed cases of pandemic influenza H1N1, including over 6000 deaths. No peak in activity has been seen. The most common causes of death are pneumonia and acute respiratory distress syndrome. We report a case of a 55-year-old woman who presented with organising pneumonia associated with influenza A (H1N1) infection confirmed by transbronchial lung biopsy. Organising pneumonia should also be considered as a possible complication of influenza A (H1N1) infection, given that these patients can benefit from early diagnosis and appropriate specific management.

Pandemic influenza A/H1N1pdm in Italy: age, risk and population susceptibility.

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Stefano Merler

Full Text Available BACKGROUND: A common pattern emerging from several studies evaluating the impact of the 2009 A/H1N1 pandemic influenza (A/H1N1pdm conducted in countries worldwide is the low attack rate observed in elderly compared to that observed in children and young adults. The biological or social mechanisms responsible for the observed age-specific risk of infection are still to be deeply investigated. METHODS: The level of immunity against the A/H1N1pdm in pre and post pandemic sera was determined using left over sera taken for diagnostic purposes or routine ascertainment obtained from clinical laboratories. The antibody titres were measured by the haemagglutination inhibition (HI assay. To investigate whether certain age groups had higher risk of infection the presence of protective antibody (≥1∶40, was calculated using exact binomial 95% CI on both pre- and post- pandemic serological data in the age groups considered. To estimate age-specific susceptibility to infection we used an age-structured SEIR model. RESULTS: By comparing pre- and post-pandemic serological data in Italy we found age- specific attack rates similar to those observed in other countries. Cumulative attack rate at the end of the first A/H1N1pdm season in Italy was estimated to be 16.3% (95% CI 9.4%-23.1%. Modeling results allow ruling out the hypothesis that only age-specific characteristics of the contact network and levels of pre-pandemic immunity are responsible for the observed age-specific risk of infection. This means that age-specific susceptibility to infection, suspected to play an important role in the pandemic, was not only determined by pre-pandemic levels of H1N1pdm antibody measured by HI. CONCLUSIONS: Our results claim for new studies to better identify the biological mechanisms, which might have determined the observed pattern of susceptibility with age. Moreover, our results highlight the need to obtain early estimates of differential susceptibility with age in

(H1N1) Influenza in Saurashtra, India

African Journals Online (AJOL)

Mexico in April, 2009,[1] and then in United States (US).[2,3]. This was originally ... duration of hospital stay of such patients was 2‑32 days. All admitted A (H1N1) .... Because of limited resources, only 2009 A (H1N1) influenza virus was tested ...

Predictors of H1N1 influenza in the emergency department: proposition for a modified H1N1 case definition.

Science.gov (United States)

Flick, H; Drescher, M; Prattes, J; Tovilo, K; Kessler, H H; Vander, K; Seeber, K; Palfner, M; Raggam, R B; Avian, A; Krause, R; Hoenigl, M

2014-02-01

Reliable and rapid diagnosis of influenza A H1N1 is essential to initiate appropriate antiviral therapy and preventive measures. We analysed the differences in clinical presentation and laboratory parameters between emergency department patients with PCR-confirmed H1N1 influenza infection (n = 199) and those with PCR-negative influenza-like illness (ILI; n = 252). Cough, wheezing, leucopenia, eosinopenia and a lower C-reactive protein remained significant predictors of H1N1 influenza. Proposed combinations of clinical symptoms with simple laboratory parameters (e.g. reported or measured fever and either cough or leucocytes definitions that use clinical criteria alone. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Events supposedly attributable to vaccination or immunization during pandemic influenza A (H1N1) vaccination campaigns in Latin America and the Caribbean.

Science.gov (United States)

Ropero-Álvarez, A M; Whittembury, A; Bravo-Alcántara, P; Kurtis, H J; Danovaro-Holliday, M C; Velandia-González, M

2015-01-01

As part of the vaccination activities against influenza A[H1N1]pdm vaccine in 2009-2010, countries in Latin American and the Caribbean (LAC) implemented surveillance of events supposedly attributable to vaccines and immunization (ESAVI). We describe the serious ESAVI reported in LAC in order to further document the safety profile of this vaccine and highlight lessons learned. We reviewed data from serious H1N1 ESAVI cases from LAC countries reported to the Pan American Health Organization/World Health Organization. We estimated serious ESAVI rates by age and target group, as well as by clinical diagnosis, and completed descriptive analyses of final outcomes and classifications given in country. A total of 1000 serious ESAVI were reported by 18 of the 29 LAC countries that vaccinated against A[H1N1]pdm. The overall reporting rate in LAC was 6.91 serious ESAVI per million doses, with country reporting rates ranging from 0.77 to 64.68 per million doses. Rates were higher among pregnant women (16.25 per million doses) when compared to health care workers (13.54 per million doses) and individuals with chronic disease (4.03 per million doses). The top three most frequent diagnoses were febrile seizures (12.0%), Guillain-Barré Syndrome (10.5%) and acute pneumonia (8.0%). Almost half (49.1%) of the serious ESAVI were reported among children aged ESAVI reported, 37.8% were classified as coincidental, 35.3% as related to vaccine components, 26.4% as non-conclusive and 0.5% as a programmatic error. This regional overview of A[H1N1]pdm vaccine safety data in LAC estimated the rate of serious ESAVI at lower levels than other studies. However, the ESAVI diagnosis distribution is comparable to the published literature. Lessons learned can be applied in the response to future pandemics. Copyright © 2014. Published by Elsevier Ltd.

Immunization-Safety Monitoring Systems for the 2009 H1N1 Monovalent Influenza Vaccination Program

NARCIS (Netherlands)

Salmon, Daniel A.; Akhtar, Aysha; Mergler, Michelle J.; Vannice, Kirsten S.; Izurieta, Hector; Ball, Robert; Lee, Grace M.; Vellozzi, Claudia; Garman, Patrick; Cunningham, Francesca; Gellin, Bruce; Koh, Howard; Lurie, Nicole

The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by

Expression of H5 hemagglutinin vaccine antigen in common duckweed (Lemna minor) protects against H5N1 high pathogenicity avian influenza virus challenge in immunized chickens.

Science.gov (United States)

Bertran, Kateri; Thomas, Colleen; Guo, Xuan; Bublot, Michel; Pritchard, Nikki; Regan, Jeffrey T; Cox, Kevin M; Gasdaska, John R; Dickey, Lynn F; Kapczynski, Darrell R; Swayne, David E

2015-07-09

A synthetic hemagglutinin (HA) gene from the highly pathogenic avian influenza (HPAI) virus A/chicken/Indonesia/7/2003 (H5N1) (Indo/03) was expressed in aquatic plant Lemna minor (rLemna-HA). In Experiment 1, efficacy of rLemna-HA was tested on birds immunized with 0.2μg or 2.3 μg HA and challenged with 10(6) mean chicken embryo infectious doses (EID50) of homologous virus strain. Both dosages of rLemna-HA conferred clinical protection and dramatically reduced viral shedding. Almost all the birds immunized with either dosage of rLemna-HA elicited HA antibody titers against Indo/03 antigen, suggesting an association between levels of anti-Indo/03 antibodies and protection. In Experiment 2, efficacy of rLemna-HA was tested on birds immunized with 0.9 μg or 2.2 μg HA and challenged with 10(6) EID50 of heterologous H5N1 virus strains A/chicken/Vietnam/NCVD-421/2010 (VN/10) or A/chicken/West Java/PWT-WIJ/2006 (PWT/06). Birds challenged with VN/10 exhibited 100% survival regardless of immunization dosage, while birds challenged with PWT/06 had 50% and 30% mortality at 0.9 μg HA and 2.2 μg HA, respectively. For each challenge virus, viral shedding titers from 2.2 μg HA vaccinated birds were significantly lower than those from 0.9μg HA vaccinated birds, and titers from both immunized groups were in turn significantly lower than those from sham vaccinated birds. Even if immunized birds elicited HA titers against the vaccine antigen Indo/03, only the groups challenged with VN/10 developed humoral immunity against the challenge antigen. None (rLemna-HA 0.9 μg HA) and 40% (rLemna-HA 2.2 μg HA) of the immunized birds challenged with PWT/06 elicited pre-challenge antibody titers, respectively. In conclusion, Lemna-expressed HA demonstrated complete protective immunity against homologous challenge and suboptimal protection against heterologous challenge, the latter being similar to results from inactivated whole virus vaccines. Transgenic duckweed-derived HA could be a

The rate coefficients for the processes of (n - n')-mixing in collisions of Rydberg atoms H*(n) with H(1s) atoms

International Nuclear Information System (INIS)

Mihajlov, A A; Ignjatovic, Lj M; Djuric, Z; Ljepojevic, N N

2004-01-01

This paper presents the results of semi-classical calculations of rate coefficients of (n - n')-mixing processes in collisions of Rydberg atoms H*(n) with H(1s) atoms. These processes have been modelled by the mechanism of the resonant energy exchange within the electron component of the H*(n) + H collisional system. The calculations of the rate coefficients, based on this model, were performed for the series of principal quantum numbers, n and n', and atomic, T a , and electronic, T e , temperatures. It was shown that these processes can be of significant influence on the populations of Rydberg atoms in weakly ionized plasmas (ionization degree ∼ -4 ), and therefore have to be included in appropriate models of such plasmas

In vitro reassortment between endemic H1N2 and 2009 H1N1 pandemic swine influenza viruses generates attenuated viruses.

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Ben M Hause

Full Text Available The pandemic H1N1 (pH1N1 influenza virus was first reported in humans in the spring of 2009 and soon thereafter was identified in numerous species, including swine. Reassortant viruses, presumably arising from the co-infection of pH1N1 and endemic swine influenza virus (SIV, were subsequently identified from diagnostic samples collected from swine. In this study, co-infection of swine testicle (ST cells with swine-derived endemic H1N2 (MN745 and pH1N1 (MN432 yielded two reassortant H1N2 viruses (R1 and R2, both possessing a matrix gene derived from pH1N1. In ST cells, the reassortant viruses had growth kinetics similar to the parental H1N2 virus and reached titers approximately 2 log(10 TCID(50/mL higher than the pH1N1 virus, while in A549 cells these viruses had similar growth kinetics. Intranasal challenge of pigs with H1N2, pH1N1, R1 or R2 found that all viruses were capable of infecting and transmitting between direct contact pigs as measured by real time reverse transcription PCR of nasal swabs. Lung samples were also PCR-positive for all challenge groups and influenza-associated microscopic lesions were detected by histology. Interestingly, infectious virus was detected in lung samples for pigs challenged with the parental H1N2 and pH1N1 at levels significantly higher than either reassortant virus despite similar levels of viral RNA. Results of our experiment suggested that the reassortant viruses generated through in vitro cell culture system were attenuated without gaining any selective growth advantage in pigs over the parental lineages. Thus, reassortant influenza viruses described in this study may provide a good system to study genetic basis of the attenuation and its mechanism.

H1N1, H3N2 et B à Abidjan, Côte d'Ivoire

African Journals Online (AJOL)

English Title: Comparative analysis of the epidemiological and clinical profiles of influenza infection due to 2009 pH1N1, H1N1, H3N2 and B viruses in Abidjan, Cote d'Ivoire. English Abstract. Influenza can have various epidemiological and clinical characteristics. This study compares the epidemio-clinical profiles of ...

Fusion plasma physics research on the H-1 national facility

International Nuclear Information System (INIS)

Harris, J.

1998-01-01

Full text: Australia has a highly leveraged fusion plasma research program centred on the H-1 National Facility device at the ANU. H-1 is a heliac, a novel helical axis stellarator that was experimentally pioneered in Australia, but has a close correlation with the worldwide research program on toroidal confinement of fusion grade plasma. Experiments are conducted on H-1 by university researchers from the Australian Fusion Research Group (comprising groups from the ANU, the Universities of Sydney, Western Sydney, Canberra, New England, and Central Queensland University) under the aegis of AINSE; the scientists also collaborate with fusion researchers from Japan and the US. Recent experiments on H-1 have focused on improved confinement modes that can be accessed at very low powers in H-1, but allow the study of fundamental physics effects seen on much larger machines at higher powers. H-1 is now being upgraded in magnetic field and heating power, and will be able to confine hotter plasmas beginning in 1999, offering greatly enhanced research opportunities for Australian plasma scientists and engineers, with substantial spillover of ideas from fusion research into other areas of applied physics and engineering

Preparasi Imunoglobulin G Kelinci sebagai Antigen Penginduksi Antibodi Spesifik Terhadap Virus Avian Influenza H5N1 Strain Legok

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Ketut Karuni Nyanakumari Natih

2010-06-01

Full Text Available The aim of this research was to prepare rabbit Immunoglobulin G as anti-idiotype antibody (Ab2 ofAvian Influenza Virus (AIV H5N1. A polyclonal antibody was collected from guinea pigs immunized withinactivated AI vaccine H5N1of Legok strain. Antibody of H5N1 AI in serum was detected by Agar gelprecipitation test (AGPT and an Inhibition Hemmaglutination test (IHT. The highest titre of antibodywas obtained one week after the third immunization. Serum of guinea pigs containing IgG was purifiedusing the Montage Antibody purification kit & spin column with Prosep A media (Millipore. The AI H5N1IgG concentration was 8 mg/ml. AI H5N1 IgG, was then digested with pepsin to obtain F(ab2 fraction andwas called Ab1. The concentration of IgG and F(ab2 and purity of IgG were determined by UVspectrophotometer which showed Ab1 concentration 1 mg/ml. Molecular weight was estimated by sodiumdodecyl sulfate- polyacrilamide gel electrophoresis (SDS-PAGE. Ab2 was produced by immunization ofrabbit with Ab1. The first immunization was carried out by subcutaneous injection with 500 ?g of Ab1emulsified in Complete Freund Adjuvant. The immunization was repeated with the same dose of Ab1emulsified in Incomplete Freund Adjuvan at 1 week intervals. One week after the second immunization,rabbit’s serum was harvested and IgG was purified using the Montage Antibody purification kit & spincolumn with Prosep A media (Millipore. The rabbit IgG, called Ab2, was an anti-idiotypic antibody againstAIV-H5N1. In AGPT, a precipitation line appeared between Ab1 and Ab2. A partial reaction appearedbetween Ab2 and the AI H5N1 antigen was also detected. The results indicated that Ab2 is a possiblecandidate of imunogen for protection against an AI virus H5N1 infection.

Different neuraminidase inhibitor susceptibilities of human H1N1, H1N2, and H3N2 influenza A viruses isolated in Germany from 2001 to 2005/2006.

Science.gov (United States)

Bauer, Katja; Richter, Martina; Wutzler, Peter; Schmidtke, Michaela

2009-04-01

In the flu season 2005/2006 amantadine-resistant human influenza A viruses (FLUAV) of subtype H3N2 circulated in Germany. This raises questions on the neuraminidase inhibitor (NAI) susceptibility of FLUAV. To get an answer, chemiluminescence-based neuraminidase inhibition assays were performed with 51 H1N1, H1N2, and H3N2 FLUAV isolated in Germany from 2001 to 2005/2006. According to the mean IC(50) values (0.38-0.91 nM for oseltamivir and 0.76-1.13 nM for zanamivir) most H1N1 and H3N2 FLUAV were NAI-susceptible. But, about four times higher zanamivir concentrations were necessary to inhibit neuraminidase activity of H1N2 viruses. Two H1N1 isolates were less susceptible to both drugs in NA inhibition as well as virus yield reduction assays. Results from sequence analysis of viral hemagglutinin and neuraminidase genes and evolutionary analysis of N2 gene revealed (i) different subclades for N2 in H1N2 and H3N2 FLUAV that could explain the differences in zanamivir susceptibility among these viruses and (ii) specific amino acid substitutions in the neuraminidase segment of the two less NAI-susceptible H1N1 isolates. One H3N2 was isolate proved to be a mixture of a NA deletion mutant and full-length NA viruses.

Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth.

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Donna J Curtis

Full Text Available We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children.Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI titers, avidity indices (AI, B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1.At entry, 26 (29% subjects had pH1N1 protective HAI titers (≥1:40. pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p<0.05, but IgA ASC, IL-5, IL-13, IL-21, IFNγ and B-cell subsets did not change. Subjects with baseline HAI ≥1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI <1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNγ, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNγ responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets.HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI≥1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent

Immune escape mutants of Highly Pathogenic Avian Influenza H5N1 selected using polyclonal sera: identification of key amino acids in the HA protein.

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Ioannis Sitaras

Full Text Available Evolution of Avian Influenza (AI viruses--especially of the Highly Pathogenic Avian Influenza (HPAI H5N1 subtype--is a major issue for the poultry industry. HPAI H5N1 epidemics are associated with huge economic losses and are sometimes connected to human morbidity and mortality. Vaccination (either as a preventive measure or as a means to control outbreaks is an approach that splits the scientific community, due to the risk of it being a potential driving force in HPAI evolution through the selection of mutants able to escape vaccination-induced immunity. It is therefore essential to study how mutations are selected due to immune pressure. To this effect, we performed an in vitro selection of mutants from HPAI A/turkey/Turkey/1/05 (H5N1, using immune pressure from homologous polyclonal sera. After 42 rounds of selection, we identified 5 amino acid substitutions in the Haemagglutinin (HA protein, most of which were located in areas of antigenic importance and suspected to be prone to selection pressure. We report that most of the mutations took place early in the selection process. Finally, our antigenic cartography studies showed that the antigenic distance between the selected isolates and their parent strain increased with passage number.

The critical role of Notch ligand Delta-like 1 in the pathogenesis of influenza A virus (H1N1 infection.

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Toshihiro Ito

2011-11-01

Full Text Available Influenza A viral infections have been identified as the etiologic agents for historic pandemics, and contribute to the annual mortality associated with acute viral pneumonia. While both innate and acquired immunity are important in combating influenza virus infection, the mechanism connecting these arms of the immune system remains unknown. Recent data have indicated that the Notch system is an important bridge between antigen-presenting cells (APCs and T cell communication circuits and plays a central role in driving the immune system to overcome disease. In the present study, we examine the role of Notch signaling during influenza H1N1 virus infection, focusing on APCs. We demonstrate here that macrophages, but not dendritic cells (DCs, increased Notch ligand Delta-like 1 (Dll1 expression following influenza virus challenge. Dll1 expression on macrophages was dependent on retinoic acid-inducible gene-I (RIG-I induced type-I IFN pathway, and not on the TLR3-TRIF pathway. We also found that IFNα-Receptor knockout mice failed to induce Dll1 expression on lung macrophages and had enhanced mortality during influenza virus infection. Our results further showed that specific neutralization of Dll1 during influenza virus challenge induced higher mortality, impaired viral clearance, and decreased levels of IFN-γ. In addition, we blocked Notch signaling by using γ-secretase inhibitor (GSI, a Notch signaling inhibitor. Intranasal administration of GSI during influenza infection also led to higher mortality, and higher virus load with excessive inflammation and an impaired production of IFN-γ in lungs. Moreover, Dll1 expression on macrophages specifically regulates IFN-γ levels from CD4(+and CD8(+T cells, which are important for anti-viral immunity. Together, the results of this study show that Dll1 positively influences the development of anti-viral immunity, and may provide mechanistic approaches for modifying and controlling the immune response

Progress toward a universal H5N1 vaccine: a recombinant modified vaccinia virus Ankara-expressing trivalent hemagglutinin vaccine.

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Mookkan Prabakaran

Full Text Available The rapid evolution of new sublineages of H5N1 influenza poses the greatest challenge in control of H5N1 infection by currently existing vaccines. To overcome this, an MVAtor vector expressing three H5HA antigens A/Vietnam/1203/04, A/Indonesia/669/06 and A/Anhui/01/05 (MVAtor-tri-HA vector was developed to elicit broad cross-protection against diverse clades by covering amino acid variations in the major neutralizing epitopes of HA among H5N1 subtypes.BALB/c mice and guinea pigs were immunized i.m. with 8×107 TCID50/animal of MVAtor-tri-HA vector. The immunogenicity and cross-protective immunity of the MVAtor-tri-HA vector was evaluated against diverse clades of H5N1 strains.The results showed that mice immunized with MVAtor-tri-HA vector induced robust cross-neutralizing immunity to diverse H5N1 clades. In addition, the MVAtor-tri-HA vector completely protected against 10 MLD50 of a divergent clade of H5N1 infection (clade 7. Importantly, the serological surveillance of post-vaccinated guinea pig sera demonstrated that MVAtor-tri-HA vector was able to elicit strong cross-clade neutralizing immunity against twenty different H5N1 strains from six clades that emerged between 1997 and 2012.The present findings revealed that incorporation of carefully selected HA genes from divergent H5N1 strains within a single vector could be an effective approach in developing a vaccine with broad coverage to prevent infection during a pandemic situation.

CD4+/CD8+ T lymphocytes imbalance in children with severe 2009 pandemic influenza A (H1N1 pneumonia

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Ji Eun Kim

2011-05-01

Full Text Available Purpose : This study was conducted to investigate the immune responses of children with moderate and severe novel influenza A virus (H1N1 pneumonia, and to compare their clinical and immunological findings with those of control subjects. Methods : Thirty-two admitted patients with H1N1 pneumonia were enrolled in the study. The clinical profiles, humoral and cell-mediated immune responses of the 16 H1N1 pneumonia patients who were admitted to the pediatric intensive care unit (severe pneumonia group, 16 H1N1 pneumonia patients admitted to the pediatric general ward (moderate pneumonia group and 13 control subjects (control group were measured. Results : Total lymphocyte counts were significantly lower in patients with H1N1 pneumonia than in the control group (P=0.02. The number of CD4+ T lymphocytes was significantly lower in the severe pneumonia group (411.5±253.5/μL than in the moderate pneumonia (644.9±291.1/μL, P=0.04 and control (902.5±461.2/μL, P=0.01 groups. However, the number of CD8+ T lymphocytes was significantly higher in the severe pneumonia group (684.2±420.8/μL than in the moderate pneumonia (319.7±176.6/μL, P=0.02 and control (407.2±309.3/μL, P=0.03 groups. The CD4+/CD8+ T lymphocytes ratio was significantly lower in the severe pneumonia group (0.86±0.24 than in the moderate pneumonia (1.57±0.41, P=0.01 and control (1.61±0.49, P=0.01 groups. The serum levels of immunoglobulin G, immunoglobulin M and immunoglobulin E were significantly higher in the severe pneumonia group than in the 2 other groups. Conclusion : The results of this study suggest that increased humoral immune responses and the differences in the CD4+ and CD8+ T lymphocyte profiles, and imbalance of their ratios may be related to the severity of H1N1 pneumonia in children.

Predicting H1N1 vaccine uptake and H1N1-related health beliefs: the role of individual difference in consideration of future consequences.

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Nan, Xiaoli; Kim, Jarim

2014-01-01

This research examines the influence of individual difference in consideration of future consequences on H1N1 vaccine uptake and H1N1-related health beliefs (i.e., perceived susceptibility to and severity of the H1N1 flu, perceived efficacy and safety of the H1N1 vaccine, and perceived self-efficacy in obtaining the H1N1 vaccine). A survey of 411 college students showed that consideration of future consequences had no direct effect on vaccine uptake, but higher consideration of future consequences was associated with greater perceived severity of the flu, higher perceived effectiveness of the vaccine, and greater perceived self-efficacy. Additional analysis suggested that consideration of future consequences had a significant indirect effect on vaccine uptake through perceived vaccine efficacy. Results of the study also revealed gender and racial differences in some of the H1N1-related health beliefs. Implications of the findings for vaccine risk communication are discussed.

Presence of serum antibodies to influenza A subtypes H5 and N1 in swans and ibises in French wetlands, irrespective of highly pathogenic H5N1 natural infection.

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Niqueux, Eric; Guionie, Olivier; Schmitz, Audrey; Hars, Jean; Jestin, Véronique

2010-03-01

difference could be shown for swans from the outbreak areas sampled in 2006 and 2007. These results suggest that ibises and swans from areas without declared outbreaks had acquired humoral immunity after AIV infections with subtypes H5 and N1 but independently from HP H5N1 infection. However, for swans living in outbreak areas, it cannot be excluded that this immunity might result from either a subclinical or a nonlethal infection by HP H5N1.

Intensive cytokine induction in pandemic H1N1 influenza virus infection accompanied by robust production of IL-10 and IL-6.

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Yu, Xuelian; Zhang, Xi; Zhao, Baihui; Wang, Jiayu; Zhu, Zhaokui; Teng, Zheng; Shao, Junjie; Shen, Jiaren; Gao, Ye; Yuan, Zhengan; Wu, Fan

2011-01-01

The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1)] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1) are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1) patients and identified cytokines related to disease severity. We retrieved 77, 59, 26 and 26 sera samples from P(H1N1) and non-flu influenza like illness (non-ILIs) cases with mild symptoms (mild patients), P(H1N1) vaccinees and healthy individuals, respectively. Nine and 16 sera were from hospitalized P(H1N1) and non-ILIs patients with severe symptoms (severe patients). Cytokines of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were assayed by cytokine bead array, IL-17 and IL-23 measured with ELISA. Mild P(H1N1) patients produced significantly elevated IL-2, IL-12, IFN-γ, IL-6, TNF-α, IL-5, IL-10, IL-17 and IL-23 versus to healthy controls. While an overwhelming IL-6 and IL-10 production were observed in severe P(H1N1) patients. Higher IL-10 secretion in P(H1N1) vaccinees confirmed our observation that highly increased level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression. A comprehensive innate immune response was activated at the early stage of P(H1N1) infection with a combine Th1/Th2/Th3 cytokines production. As disease progression, a systemic production of IL-6 and IL-10 were observed in severe P(H1N1) patients. Further analysis found a strong correlation between IL-6 and IL-10 production in the severe P(H1N1) patients. IL-6 may be served as a mediator to induce IL-10 production. Highly elevated level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression, but the underlying mechanism awaits further detailed investigations.

Intensive cytokine induction in pandemic H1N1 influenza virus infection accompanied by robust production of IL-10 and IL-6.

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Xuelian Yu

Full Text Available BACKGROUND: The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1 are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1 patients and identified cytokines related to disease severity. METHODS AND PRINCIPAL FINDINGS: We retrieved 77, 59, 26 and 26 sera samples from P(H1N1 and non-flu influenza like illness (non-ILIs cases with mild symptoms (mild patients, P(H1N1 vaccinees and healthy individuals, respectively. Nine and 16 sera were from hospitalized P(H1N1 and non-ILIs patients with severe symptoms (severe patients. Cytokines of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were assayed by cytokine bead array, IL-17 and IL-23 measured with ELISA. Mild P(H1N1 patients produced significantly elevated IL-2, IL-12, IFN-γ, IL-6, TNF-α, IL-5, IL-10, IL-17 and IL-23 versus to healthy controls. While an overwhelming IL-6 and IL-10 production were observed in severe P(H1N1 patients. Higher IL-10 secretion in P(H1N1 vaccinees confirmed our observation that highly increased level of sera IL-6 and IL-10 in P(H1N1 patients may lead to disease progression. CONCLUSION AND SIGNIFICANCE: A comprehensive innate immune response was activated at the early stage of P(H1N1 infection with a combine Th1/Th2/Th3 cytokines production. As disease progression, a systemic production of IL-6 and IL-10 were observed in severe P(H1N1 patients. Further analysis found a strong correlation between IL-6 and IL-10 production in the severe P(H1N1 patients. IL-6 may be served as a mediator to induce IL-10 production. Highly elevated level of sera IL-6 and IL-10 in P(H1N1 patients may lead to disease progression, but the underlying mechanism awaits

The rate coefficients for the processes of (n - n')-mixing in collisions of Rydberg atoms H*(n) with H(1s) atoms

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Mihajlov, A A [Institute of Physics, PO Box 57, 11001 Belgrade (Serbia and Montenegro); Ignjatovic, Lj M [Institute of Physics, PO Box 57, 11001 Belgrade (Serbia and Montenegro); Djuric, Z [Silvaco Data Systems, Compass Point, St Ives PE27 5JL (United Kingdom); Ljepojevic, N N [Silvaco Data Systems, Compass Point, St Ives PE27 5JL (United Kingdom)

2004-11-28

This paper presents the results of semi-classical calculations of rate coefficients of (n - n')-mixing processes in collisions of Rydberg atoms H*(n) with H(1s) atoms. These processes have been modelled by the mechanism of the resonant energy exchange within the electron component of the H*(n) + H collisional system. The calculations of the rate coefficients, based on this model, were performed for the series of principal quantum numbers, n and n', and atomic, T{sub a}, and electronic, T{sub e}, temperatures. It was shown that these processes can be of significant influence on the populations of Rydberg atoms in weakly ionized plasmas (ionization degree {approx}<10{sup -4}), and therefore have to be included in appropriate models of such plasmas.

Effect of priming with H1N1 influenza viruses of variable antigenic distances on challenge with 2009 pandemic H1N1 virus.

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O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice N; Wei, Chih-Jen; Nabel, Gary J; Subbarao, Kanta

2012-08-01

Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.

Identification of swine H1N2/pandemic H1N1 reassortant influenza virus in pigs, United States.

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Ali, Ahmed; Khatri, Mahesh; Wang, Leyi; Saif, Yehia M; Lee, Chang-Won

2012-07-06

In October and November 2010, novel H1N2 reassortant influenza viruses were identified from pigs showing mild respiratory signs that included cough and depression. Sequence and phylogenetic analysis showed that the novel H1N2 reassortants possesses HA and NA genes derived from recent H1N2 swine isolates similar to those isolated from Midwest. Compared to the majority of reported reassortants, both viruses preserved human-like host restrictive and putative antigenic sites in their HA and NA genes. The four internal genes, PB2, PB1, PA, and NS were similar to the contemporary swine triple reassortant viruses' internal genes (TRIG). Interestingly, NP and M genes of the novel reassortants were derived from the 2009 pandemic H1N1. The NP and M proteins of the two isolates demonstrated one (E16G) and four (G34A, D53E, I109T, and V313I) amino acid changes in the M2 and NP proteins, respectively. Similar amino acid changes were also noticed upon incorporation of the 2009 pandemic H1N1 NP in other reassortant viruses reported in the U.S. Thus the role of those amino acids in relation to host adaptation need to be further investigated. The reassortments of pandemic H1N1 with swine influenza viruses and the potential of interspecies transmission of these reassortants from swine to other species including human indicate the importance of systematic surveillance of swine population to determine the origin, the prevalence of similar reassortants in the U.S. and their impact on both swine production and public health. Copyright © 2012 Elsevier B.V. All rights reserved.

CYTOKINE LEVELS IN BLOOD (IFNγ, TNFα, IL-10 AND INTERCELLULAR ADHESION MOLECULE (sICAM-1 IN PATIENTS WITH PNEUMONIA INFLUENZA A/H1N1

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E. N. Romanova

2012-01-01

Full Text Available Abstract. The changes of cytokine profile revealed in viral influenza-associated pneumonia (A/H1N1 were shown to exceed appropriate parameters for the cases of bacterial outpatient pneumonia. The most expressed hyperproduction of proinflammatory cytokines (IFNγ, TNFα, and a marker of pathological endothelial activation (sICAM-1 was registered in more severe cases, including those with ALI/ARDS, thus confirming a prognostic value of these parameters. An increased level of IL-10 and decreased IFNγ and TNFα concentrations in the non-severe flu-like pneumonia are indicative for a more balanced immune response. Increased IFNγ concentrations at six months after influenza-associated pneumonia (A/H1N1 may be caused by prolonged use of interferon inducers, as well as persistent antiviral immunity.

H5N1 whole-virus vaccine induces neutralizing antibodies in humans which are protective in a mouse passive transfer model.

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M Keith Howard

Full Text Available BACKGROUND: Vero cell culture-derived whole-virus H5N1 vaccines have been extensively tested in clinical trials and consistently demonstrated to be safe and immunogenic; however, clinical efficacy is difficult to evaluate in the absence of wide-spread human disease. A lethal mouse model has been utilized which allows investigation of the protective efficacy of active vaccination or passive transfer of vaccine induced sera following lethal H5N1 challenge. METHODS: We used passive transfer of immune sera to investigate antibody-mediated protection elicited by a Vero cell-derived, non-adjuvanted inactivated whole-virus H5N1 vaccine. Mice were injected intravenously with H5N1 vaccine-induced rodent or human immune sera and subsequently challenged with a lethal dose of wild-type H5N1 virus. RESULTS: Passive transfer of H5N1 vaccine-induced mouse, guinea pig and human immune sera provided dose-dependent protection of recipient mice against lethal challenge with wild-type H5N1 virus. Protective dose fifty values for serum H5N1 neutralizing antibody titers were calculated to be ≤1∶11 for all immune sera, independently of source species. CONCLUSIONS: These data underpin the confidence that the Vero cell culture-derived, whole-virus H5N1 vaccine will be effective in a pandemic situation and support the use of neutralizing serum antibody titers as a correlate of protection for H5N1 vaccines.

Influenza A (H1N1) neuraminidase inhibitors from Vitis amurensis

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Nguyen, Ngoc Anh; Dao, Trong Tuan; Tung, Bui Thanh

2011-01-01

Recently, a novel H1N1 influenza A virus (H1N1/09 virus) was identified and considered a strong candidate for a novel influenza pandemic. As part of an ongoing anti-influenza screening programme on natural products, eight oligostilbenes were isolated as active principles from the methanol extract...... of Vitis amurensis. This manuscript reports the isolation, structural elucidation, and anti-viral activities of eight compounds on various neuraminidases from influenza A/PR/8/34 (H1N1), novel swine-origin influenza A (H1N1), and oseltamivir-resistant novel H1N1 (H274Y) expressed in 293T cells...

FDG uptake in axillary lymph nodes after vaccination against pandemic (H1N1)

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Panagiotidis, Emmanouil; Exarhos, Demetrios; Housianakou, Irene; Bournazos, Apostolos; Datseris, Ioannis

2010-01-01

To alert the imaging community to potential false positive findings related to current immunization programmes against H1N1 influenza virus. We reviewed 10 patients referred for positron emission tomography/computed tomography (PET/CT) who had undergone recent vaccination. All studies showed 18 F-fluorodeoxyglucose (FDG) uptake in the draining axillary lymph nodes close to the vaccination site, while low-dose CT revealed lymph nodes ranged between 0.5 cm and 1.2 cm at the same site. This potential pitfall in PET/CT should be borne in mind during current vaccination programmes. (orig.)

Protection of chickens against H5N1 highly pathogenic avian influenza virus infection by live vaccination with infectious laryngotracheitis virus recombinants expressing H5 hemagglutinin and N1 neuraminidase.

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Pavlova, Sophia P; Veits, Jutta; Keil, Günther M; Mettenleiter, Thomas C; Fuchs, Walter

2009-01-29

Attenuated vaccine strains of the alphaherpesvirus causing infectious laryngotracheitis of chickens (ILTV, gallid herpesvirus 1) can be used for mass application. Previously, we showed that live virus vaccination with recombinant ILTV expressing hemagglutinin of highly pathogenic avian influenza viruses (HPAIV) protected chickens against ILT and fowl plague caused by HPAIV carrying the corresponding hemagglutinin subtypes [Lüschow D, Werner O, Mettenleiter TC, Fuchs W. Protection of chickens from lethal avian influenza A virus infection by live-virus vaccination with infectious laryngotracheitis virus recombinants expressing the hemagglutinin (H5) gene. Vaccine 2001;19(30):4249-59; Veits J, Lüschow D, Kindermann K, Werner O, Teifke JP, Mettenleiter TC, et al. Deletion of the non-essential UL0 gene of infectious laryngotracheitis (ILT) virus leads to attenuation in chickens, and UL0 mutants expressing influenza virus haemagglutinin (H7) protect against ILT and fowl plague. J Gen Virol 2003;84(12):3343-52]. However, protection against H5N1 HPAIV was not satisfactory. Therefore, a newly designed dUTPase-negative ILTV vector was used for rapid insertion of the H5-hemagglutinin, or N1-neuraminidase genes of a recent H5N1 HPAIV isolate. Compared to our previous constructs, protein expression was considerably enhanced by insertion of synthetic introns downstream of the human cytomegalovirus immediate-early promoter within the 5'-nontranslated region of the transgenes. Deletion of the viral dUTPase gene did not affect in vitro replication of the ILTV recombinants, but led to sufficient attenuation in vivo. After a single ocular immunization, all chickens developed H5- or N1-specific serum antibodies. Nevertheless, animals immunized with N1-ILTV died after subsequent H5N1 HPAIV challenge, although survival times were prolonged compared to non-vaccinated controls. In contrast, all chickens vaccinated with either H5-ILTV alone, or H5- and N1-ILTV simultaneously, survived

Neuronal Antibodies in Children with or without Narcolepsy following H1N1-AS03 Vaccination.

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Simon Thebault

Full Text Available Type 1 narcolepsy is caused by deficiency of hypothalamic orexin/hypocretin. An autoimmune basis is suspected, but no specific antibodies, either causative or as biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03 vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult with type 1 narcolepsy were tested for autoantibodies to known neuronal antigens including the N-methyl-D-aspartate receptor (NMDAR and contactin-associated protein 2 (CASPR2, both associated with encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of melanin-concentrating hormone (MCH were measured. Sera from 44 H1N1-ASO3-vaccinated children without narcolepsy were also examined. None of these patients' CSFs or sera was positive for NMDAR or CASPR2 antibodies or binding to neurons; 4/13 sera bound to orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054 in orexin-deficient narcolepsy patients compared with orexin-normal children (n = 6. In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total IgG levels or in CASPR2 or NMDAR antibodies three weeks following vaccination. In conclusion, there were no narcolepsy-specific autoantibodies identified in type 1 narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children. Antibodies to other neuronal specific membrane targets, with their potential for directing use of immunotherapies, are still an important goal for future research.

Neuronal Antibodies in Children with or without Narcolepsy following H1N1-AS03 Vaccination.

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Thebault, Simon; Waters, Patrick; Snape, Matthew D; Cottrell, Dominic; Darin, Niklas; Hallböök, Tove; Huutoniemi, Anne; Partinen, Markku; Pollard, Andrew J; Vincent, Angela

2015-01-01

Type 1 narcolepsy is caused by deficiency of hypothalamic orexin/hypocretin. An autoimmune basis is suspected, but no specific antibodies, either causative or as biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03) vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult) with type 1 narcolepsy were tested for autoantibodies to known neuronal antigens including the N-methyl-D-aspartate receptor (NMDAR) and contactin-associated protein 2 (CASPR2), both associated with encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of melanin-concentrating hormone (MCH) were measured. Sera from 44 H1N1-ASO3-vaccinated children without narcolepsy were also examined. None of these patients' CSFs or sera was positive for NMDAR or CASPR2 antibodies or binding to neurons; 4/13 sera bound to orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054) in orexin-deficient narcolepsy patients compared with orexin-normal children (n = 6). In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total IgG levels or in CASPR2 or NMDAR antibodies three weeks following vaccination. In conclusion, there were no narcolepsy-specific autoantibodies identified in type 1 narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children. Antibodies to other neuronal specific membrane targets, with their potential for directing use of immunotherapies, are still an important goal for future research.

Treatment and Prevention of Pandemic H1N1 Influenza.

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Rewar, Suresh; Mirdha, Dashrath; Rewar, Prahlad

2015-01-01

Swine influenza is a respiratory infection common to pigs worldwide caused by type A influenza viruses, principally subtypes H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3. Swine influenza viruses also can cause moderate to severe illness in humans and affect persons of all age groups. People in close contact with swine are at especially high risk. Until recently, epidemiological study of influenza was limited to resource-rich countries. The World Health Organization declared an H1N1 pandemic on June 11, 2009, after more than 70 countries reported 30,000 cases of H1N1 infection. In 2015, incidence of swine influenza increased substantially to reach a 5-year high. In India in 2015, 10,000 cases of swine influenza were reported with 774 deaths. The Centers for Disease Control and Prevention recommend real-time polymerase chain reaction as the method of choice for diagnosing H1N1. Antiviral drugs are the mainstay of clinical treatment of swine influenza and can make the illness milder and enable the patient to feel better faster. Antiviral drugs are most effective when they are started within the first 48 hours after the clinical signs begin, although they also may be used in severe or high-risk cases first seen after this time. The Centers for Disease Control and Prevention recommends use of oseltamivir (Tamiflu, Genentech) or zanamivir (Relenza, GlaxoSmithKline). Prevention of swine influenza has 3 components: prevention in swine, prevention of transmission to humans, and prevention of its spread among humans. Because of limited treatment options, high risk for secondary infection, and frequent need for intensive care of individuals with H1N1 pneumonia, environmental control, including vaccination of high-risk populations and public education are critical to control of swine influenza out breaks. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Humoral and cell-mediated immunity to pandemic H1N1 influenza in a Canadian cohort one year post-pandemic: implications for vaccination.

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Lisa E Wagar

Full Text Available We evaluated a cohort of Canadian donors for T cell and antibody responses against influenza A/California/7/2009 (pH1N1 at 8-10 months after the 2nd pandemic wave by flow cytometry and microneutralization assays. Memory CD8 T cell responses to pH1N1 were detectable in 58% (61/105 of donors. These responses were largely due to cross-reactive CD8 T cell epitopes as, for those donors tested, similar recall responses were obtained to A/California 2009 and A/PR8 1934 H1N1 Hviruses. Longitudinal analysis of a single infected individual showed only a small and transient increase in neutralizing antibody levels, but a robust CD8 T cell response that rose rapidly post symptom onset, peaking at 3 weeks, followed by a gradual decline to the baseline levels seen in a seroprevalence cohort post-pandemic. The magnitude of the influenza-specific CD8 T cell memory response at one year post-pandemic was similar in cases and controls as well as in vaccinated and unvaccinated donors, suggesting that any T cell boosting from infection was transient. Pandemic H1-specific antibodies were only detectable in approximately half of vaccinated donors. However, those who were vaccinated within a few months following infection had the highest persisting antibody titers, suggesting that vaccination shortly after influenza infection can boost or sustain antibody levels. For the most part the circulating influenza-specific T cell and serum antibody levels in the population at one year post-pandemic were not different between cases and controls, suggesting that natural infection does not lead to higher long term T cell and antibody responses in donors with pre-existing immunity to influenza. However, based on the responses of one longitudinal donor, it is possible for a small population of pre-existing cross-reactive memory CD8 T cells to expand rapidly following infection and this response may aid in viral clearance and contribute to a lessening of disease severity.

Modeling of the influence of humidity on H1N1 flu in China

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PEI, Y.; Tian, H.; Xu, B.

2015-12-01

In 2009, a heavy Flu hit the whole world. It was caused by the virus H1N1. The influenza first broke out in Mexico in March and the United States in April, 2009. The World Health Organization (WHO) announced that the H1N1 influenza became pandemic, alert to a warning phase of six. By the end of 2011, 181302 H1N1 cases were reported in mainland China. To improve our understanding on the impact of environmental factors on the disease transmission, we constructed an SIR (Susceptible - Infectious - Recovered) model incorporating environmental factors. It was found that the absolute humidity was a dominant environmental factor. The study interpolated the humidity data monitored with 340 weather stations from 1951 to 2011 in mainland China. First, the break point of the trend for the absolutely humidity was detected by the BFAST (Break For Additive Season and Trend) method. Then, the SIR model with and without the absolutely humidity incorporated in the model was built and tested. Finally, the results with the two scenarios were compared. Results indicate that lower absolutely humidity may promote the transmission of the H1N1 cases. The calculated basic reproductive number ranges from 1.65 to 3.66 with a changing absolute humidity. This is consistent with the former study result with basic reproductive number ranging from 2.03 to 4.18. The average recovery duration was estimated to be 5.7 days. The average duration to get immunity from the influenza is 399.02 days. A risk map is also produced to illustrate the model results.

‘Presenting CXR phenotype of H1N1’ flu compared with contemporaneous non-H1N1, community acquired pneumonia, during pandemic and post-pandemic outbreaks’

International Nuclear Information System (INIS)

Minns, F.C.; Nimhuineachain, A; Beek, E.J.R. van; Ritchie, G.; Hill, A.; Murchison, J.T.

2015-01-01

Highlights: • Patients with H1N1 pneumonia demonstrated more opacified zones on chest x-ray than patients with non-H1N1 pneumonias. • A particular ‘phenotype’ of chest x-ray changes was identified in H1N1 patients. • This H1N1 ‘phenotype’ was the same for the two evaluated ‘flu seasons, during both pandemic and post pandemic stages. - Abstract: Aims: To review, phenotype and assess potential prognostic value of initial chest X-ray findings in patients with H1N1 influenza during seasonal outbreaks of 2009 and 2010, in comparison with non-H1N1, community acquired pneumonia (CAP). Methods: We retrospectively identified 72 patients admitted to hospital with pneumonia during the seasons of 2009 and 2010. H1N1 cases were confirmed by virology PCR. Presenting chest X-rays were jointly read by 2 radiologists, who were ‘blinded’ to further patient details and divided into 6 zones. Total number of opacified zones, the pattern and distribution of changes and length of hospital stay were recorded. Results: Patients with H1N1 demonstrated more opacified zones (mean of 2.9 compared with 2.0; p = 0.006), which were bilateral in two-thirds compared with a quarter of those with non-H1N1 CAP (p = 0.001). H1N1 radiographs were more likely to be ‘patchy’ versus ‘confluent’ changes of non-H1N1 CAP (p = 0.03) and more often demonstrated peripheral distribution (p = 0.01). H1N1 patients tended to stay in hospital longer (not significant; p = 0.08). A positive correlation existed between number of affected zones and length of inpatient stay, which was statistically significant for the cohorts combined (p = 0.02). The findings were the same for the two evaluated seasons. Conclusion: H1N1 patients demonstrated more extensive disease, which was more likely bilateral, ‘patchy’, and peripheral in distribution. With increasing global cases of H1N1, knowledge of the typical findings of the H1N1 presenting chest X-ray may assist with early triage of patients

‘Presenting CXR phenotype of H1N1’ flu compared with contemporaneous non-H1N1, community acquired pneumonia, during pandemic and post-pandemic outbreaks’

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Minns, F.C., E-mail: Fiona.Minns@nhslothian.scot.nhs.uk [Department of Radiology, New Royal Infirmary Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA (United Kingdom); Nimhuineachain, A, E-mail: draideen@gmail.com [Department of Radiology, New Royal Infirmary Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA (United Kingdom); Beek, E.J.R. van, E-mail: Edwin-vanbeek@ed.ac.uk [Clinical Research Imaging Centre, University of Edinburgh, 47 Little France Crescent, Edinburgh, Midlothian EH16 4TJ (United Kingdom); Ritchie, G., E-mail: drgillritchie@hotmail.com [Department of Radiology, New Royal Infirmary Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA (United Kingdom); Hill, A., E-mail: adam.hill318@nhs.net [Department of Respiratory Medicine, New Royal Infirmary, Edinburgh (United Kingdom); Murchison, J.T., E-mail: john.murchison@nhslothian.scot.nhs.uk [Department of Radiology, New Royal Infirmary Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA (United Kingdom)

2015-09-15

Highlights: • Patients with H1N1 pneumonia demonstrated more opacified zones on chest x-ray than patients with non-H1N1 pneumonias. • A particular ‘phenotype’ of chest x-ray changes was identified in H1N1 patients. • This H1N1 ‘phenotype’ was the same for the two evaluated ‘flu seasons, during both pandemic and post pandemic stages. - Abstract: Aims: To review, phenotype and assess potential prognostic value of initial chest X-ray findings in patients with H1N1 influenza during seasonal outbreaks of 2009 and 2010, in comparison with non-H1N1, community acquired pneumonia (CAP). Methods: We retrospectively identified 72 patients admitted to hospital with pneumonia during the seasons of 2009 and 2010. H1N1 cases were confirmed by virology PCR. Presenting chest X-rays were jointly read by 2 radiologists, who were ‘blinded’ to further patient details and divided into 6 zones. Total number of opacified zones, the pattern and distribution of changes and length of hospital stay were recorded. Results: Patients with H1N1 demonstrated more opacified zones (mean of 2.9 compared with 2.0; p = 0.006), which were bilateral in two-thirds compared with a quarter of those with non-H1N1 CAP (p = 0.001). H1N1 radiographs were more likely to be ‘patchy’ versus ‘confluent’ changes of non-H1N1 CAP (p = 0.03) and more often demonstrated peripheral distribution (p = 0.01). H1N1 patients tended to stay in hospital longer (not significant; p = 0.08). A positive correlation existed between number of affected zones and length of inpatient stay, which was statistically significant for the cohorts combined (p = 0.02). The findings were the same for the two evaluated seasons. Conclusion: H1N1 patients demonstrated more extensive disease, which was more likely bilateral, ‘patchy’, and peripheral in distribution. With increasing global cases of H1N1, knowledge of the typical findings of the H1N1 presenting chest X-ray may assist with early triage of patients

Characteristics of atopic children with pandemic H1N1 influenza viral infection: pandemic H1N1 influenza reveals 'occult' asthma of childhood.

Science.gov (United States)

Hasegawa, Shunji; Hirano, Reiji; Hashimoto, Kunio; Haneda, Yasuhiro; Shirabe, Komei; Ichiyama, Takashi

2011-02-01

The number of human cases of pandemic H1N1 influenza viral infection has increased in Japan since April 2009, as it has worldwide. This virus is widespread in the Yamaguchi prefecture in western Japan, where most infected children exhibited respiratory symptoms. Bronchial asthma is thought to be one of the risk factors that exacerbate respiratory symptoms of pandemic H1N1-infected patients, but the pathogenesis remains unclear. We retrospectively investigated the records of 33 children with pandemic H1N1 influenza viral infection who were admitted to our hospital between October and December 2009 and analyzed their clinical features. The percentage of children with asthma attack, with or without abnormal findings on chest radiographs (pneumonia, atelectasis, etc.), caused by pandemic H1N1 influenza infection was significantly higher than that of children with asthma attack and 2008-2009 seasonal influenza infection. Of the 33 children in our study, 22 (66.7%) experienced an asthma attack. Among these children, 20 (90.9%) did not receive long-term management for bronchial asthma, whereas 7 (31.8%) were not diagnosed with bronchial asthma and had experienced their first asthma attack. However, the severity of the attack did not correlate with the severity of the pulmonary complications of pandemic H1N1 influenza viral infection. The pandemic H1N1 influenza virus greatly increases the risk of lower respiratory tract complications such as asthma attack, pneumonia, and atelectasis, when compared to the seasonal influenza virus. Furthermore, our results suggest that pandemic H1N1 influenza viral infection can easily induce a severe asthma attack, pneumonia, and atelectasis in atopic children without any history of either an asthma attack or asthma treatment. © 2011 John Wiley & Sons A/S.

Enrichment of variations in KIR3DL1/S1 and KIR2DL2/L3 among H1N1/09 ICU patients: an exploratory study.

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David La

Full Text Available BACKGROUND: Infection by the pandemic influenza A (H1N1/09 virus resulted in significant pathology among specific ethnic groups worldwide. Natural Killer (NK cells are important in early innate immune responses to viral infections. Activation of NK cells, in part, depend on killer-cell immunoglobulin-like receptors (KIR and HLA class I ligand interactions. To study factors involved in NK cell dysfunction in overactive immune responses to H1N1 infection, KIR3DL1/S1 and KIR2DL2/L3 allotypes and cognate HLA ligands of H1N1/09 intensive-care unit (ICU patients were determined. METHODOLOGY AND FINDINGS: KIR3DL1/S1, KIR2DL2/L3, and HLA -B and -C of 51 H1N1/09 ICU patients and 105 H1N1-negative subjects (St. Theresa Point, Manitoba were characterized. We detected an increase of 3DL1 ligand-negative pairs (3DL1/S1(+ Bw6(+ Bw4(-, and a lack of 2DL1 HLA-C2 ligands, among ICU patients. They were also significantly enriched for 2DL2/L3 ligand-positive pairs (PVA, P=0.024, Pc=0.047; Odds Ratio:2.563, CI95%:1.109-5.923, 3DL1*00101 (Ab>VA, PSTh, P=0.034, Pc=0.268, and 3DL1*029 (Ab>STh, P=0.039, Pc=0.301. Aboriginal patients ligand-positive for 3DL1/S1 and 2DL1 had the lowest probabilities of death (R(d (R(d=28%, compared to patients that were 3DL1/S1 ligand-negative (R(d=52% or carried 3DL1*029 (R(d=52%. Relative to Caucasoids (CA, two allotypes were enriched among non-aboriginal ICU patients (NAb: 3DL1*00401 (NAb>CA, P<0.001, Pc<0.001 and 3DL1*01502 (CA1/S1, 2DL2/L3, and 2DL1 had the lowest probabilities of death (R(d=36%, compared to subjects with 3DL1*01502 (R(d=48% and/or 3DL1*00401 (R(d=58%. CONCLUSIONS: Specific KIR3DL1/S1 allotypes, 3DL1/S1 and 2DL1 ligand-negative pairs, and 2DL2/L3 ligand-positive pairs were enriched among ICU patients. This suggests a possible association with NK cell dysfunction in patients with overactive immune responses to H1N1/09, leading to

Comparison of temporal and spatial dynamics of seasonal H3N2, pandemic H1N1 and highly pathogenic avian influenza H5N1 virus infections in ferrets.

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Judith M A van den Brand

Full Text Available Humans may be infected by different influenza A viruses--seasonal, pandemic, and zoonotic--which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. Differences in spatial and temporal dynamics of these infections are poorly understood. Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1, and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi, as well as describing clinical signs and hematological parameters. H3N2 infection was restricted to the nose and peaked at 1 dpi. pH1N1 infection also peaked at 1 dpi, but occurred at similar levels throughout the respiratory tract. H5N1 infection occurred predominantly in the alveoli, where it peaked for a longer period, from 1 to 3 dpi. The associated lesions followed the same spatial distribution as virus infection, but their severity peaked between 1 and 6 days later. Neutrophil and monocyte counts in peripheral blood correlated with inflammatory cell influx in the alveoli. Of the different parameters used to measure lower respiratory tract disease, relative lung weight and affected lung tissue allowed the best quantitative distinction between the virus groups. There was extra-respiratory spread to more tissues--including the central nervous system--for H5N1 infection than for pH1N1 infection, and to none for H3N2 infection. This study shows that seasonal, pandemic, and zoonotic influenza viruses differ strongly in the spatial and temporal dynamics of infection in the respiratory tract and extra-respiratory tissues of ferrets.

Isolation and genetic characterization of avian-like H1N1 and novel ressortant H1N2 influenza viruses from pigs in China.

Science.gov (United States)

Yu, Hai; Zhang, Peng-Chao; Zhou, Yan-Jun; Li, Guo-Xin; Pan, Jie; Yan, Li-Ping; Shi, Xiao-Xiao; Liu, Hui-Li; Tong, Guang-Zhi

2009-08-21

As pigs are susceptible to both human and avian influenza viruses, they have been proposed to be intermediate hosts or mixing vessels for the generation of pandemic influenza viruses through reassortment or adaptation to the mammalian host. In this study, we reported avian-like H1N1 and novel ressortant H1N2 influenza viruses from pigs in China. Homology and phylogenetic analyses showed that the H1N1 virus (A/swine/Zhejiang/1/07) was closely to avian-like H1N1 viruses and seemed to be derived from the European swine H1N1 viruses, which was for the first time reported in China; and the two H1N2 viruses (A/swine/Shanghai/1/07 and A/swine/Guangxi/13/06) were novel ressortant H1N2 influenza viruses containing genes from the classical swine (HA, NP, M and NS), human (NA and PB1) and avian (PB2 and PA) lineages, which indicted that the reassortment among human, avian, and swine influenza viruses had taken place in pigs in China and resulted in the generation of new viruses. The isolation of avian-like H1N1 influenza virus originated from the European swine H1N1 viruses, especially the emergence of two novel ressortant H1N2 influenza viruses provides further evidence that pigs serve as intermediate hosts or "mixing vessels", and swine influenza virus surveillance in China should be given a high priority.

Identification of Human H1N2 and Human-Swine Reassortant H1N2 and H1N1 Influenza A Viruses among Pigs in Ontario, Canada (2003 to 2005)†

OpenAIRE

Karasin, Alexander I.; Carman, Suzanne; Olsen, Christopher W.

2006-01-01

Since 2003, three novel genotypes of H1 influenza viruses have been recovered from Canadian pigs, including a wholly human H1N2 virus and human-swine reassortants. These isolates demonstrate that human-lineage H1N2 viruses are infectious for pigs and that viruses with a human PB1/swine PA/swine PB2 polymerase complex can replicate in pigs.

Coadministration of Recombinant Adenovirus Expressing GM-CSF with Inactivated H5N1 Avian Influenza Vaccine Increased the Immune Responses and Protective Efficacy Against a Wild Bird Source of H5N1 Challenge.

Science.gov (United States)

Wang, Xiangwei; Wang, Xinglong; Jia, Yanqing; Wang, Chongyang; Tang, Qiuxia; Han, Qingsong; Xiao, Sa; Yang, Zengqi

2017-10-01

Wild birds play a key role in the spread of avian influenza virus (AIV). There is a continual urgent requirement for AIV vaccines to address the ongoing genetic changes of AIV. In the current study, we trialed a novel AIV vaccine against the wild bird source of H5N1 type AIV with recombinant adenovirus expressing granulocyte monocyte colony-stimulating factor (GM-CSF) as an adjuvant. A total of 150-day-old commercial chicks, with AIV-maternal-derived antibody, were divided into 6 groups. The primary vaccination was performed at day 14 followed by a subsequent boosting and intramuscular challenge on day 28 and 42, respectively. Recombinant GM-CSF (rGM-CSF) expressed by adenovirus, named as rAd-GM-CSF, raised the hemagglutination inhibition (HI) titers (log 2 ) against AIV from 7.0 (vaccinate with inactivated vaccine alone) to 8.4 after booster immunization. Moreover, the rGM-CSF addition markedly increased the expression of interferon-γ, interleukin-4, and major histocompatibility complex-II in the lungs, compared with those immunized with inactivated vaccine alone on day 29, that is, 18 h post booster immunization. Following challenge, chicks inoculated with the inactivated AIV vaccine and rAd-GM-CSF together exhibited mild clinical signs and 62% survivals compared to 33% in the group immunized with inactivated AIV vaccine alone. Higher level of HI titers, immune related molecule expressions, and protection ratio demonstrates a good potential of rGM-CSF in improving humoral and cell mediated immune responses of inactivated AIV vaccines.

Perceptions of frontline staff regarding data collection methodologies used during the 2009 A H1N1 influenza immunization campaign in Canada

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Bettinger Julie A

2010-12-01

Full Text Available Abstract Background During the 2009 H1N1 immunization campaign, electronic and hybrid (comprising both electronic and paper components systems were employed to collect client-level vaccination data in clinics across Canada. Because different systems were used across the country, the 2009 immunization campaign offered an opportunity to study the usability of the various data collection methods. Methods A convenience sample of clinic staff working in public health agencies and hospitals in 9 provinces/territories across Canada completed a questionnaire in which they indicated their level of agreement with seven statements regarding the usability of the data collection system employed at their vaccination clinic. Questions included overall ease of use, effectiveness of the method utilized, efficiency at completing tasks, comfort using the method, ability to recover from mistakes, ease of learning the method and overall satisfaction with the method. A 5-point Likert-type scale was used to measure responses. Results Most respondents (96% were employed in sites run by public health. Respondents included 186 nurses and 114 administrative staff, among whom 90% and 47%, respectively, used a paper-based method for data collection. Approximately half the respondents had a year or less of experience with immunization-related tasks during seasonal influenza campaigns. Over 90% of all frontline staff found their data collection method easy to use, perceived it to be effective in helping them complete their tasks, felt quick and comfortable using the method, and found the method easy to learn, regardless of whether a hybrid or electronic system was used. Conclusions This study demonstrates that there may be a greater willingness of frontline immunization staff to adapt to new technologies than previously perceived by decision-makers. The public health community should recognize that usability may not be a barrier to implementing electronic methods for

Mannose-binding lectin contributes to deleterious inflammatory response in pandemic H1N1 and avian H9N2 infection.

Science.gov (United States)

Ling, Man To; Tu, Wenwei; Han, Yan; Mao, Huawei; Chong, Wai Po; Guan, Jing; Liu, Ming; Lam, Kwok Tai; Law, Helen K W; Peiris, J S Malik; Takahashi, K; Lau, Yu Lung

2012-01-01

Mannose-binding lectin (MBL) is a pattern-recognition molecule, which functions as a first line of host defense. Pandemic H1N1 (pdmH1N1) influenza A virus caused massive infection in 2009 and currently circulates worldwide. Avian influenza A H9N2 (H9N2/G1) virus has infected humans and has the potential to be the next pandemic virus. Antiviral function and immunomodulatory role of MBL in pdmH1N1 and H9N2/G1 virus infection have not been investigated. In this study, MBL wild-type (WT) and MBL knockout (KO) murine models were used to examine the role of MBL in pdmH1N1 and H9N2/G1 virus infection. Our study demonstrated that in vitro, MBL binds to pdmH1N1 and H9N2/G1 viruses, likely via the carbohydrate recognition domain of MBL. Wild-type mice developed more severe disease, as evidenced by a greater weight loss than MBL KO mice during influenza virus infection. Furthermore, MBL WT mice had enhanced production of proinflammatory cytokines and chemokines compared with MBL KO mice, suggesting that MBL could upregulate inflammatory responses that may potentially worsen pdmH1N1 and H9N2/G1 virus infections. Our study provided the first in vivo evidence that MBL may be a risk factor during pdmH1N1 and H9N2/G1 infection by upregulating proinflammatory response.

Genetic and biological characterisation of an avian-like H1N2 swine influenza virus generated by reassortment of circulating avian-like H1N1 and H3N2 subtypes in Denmark.

Science.gov (United States)

Trebbien, Ramona; Bragstad, Karoline; Larsen, Lars Erik; Nielsen, Jens; Bøtner, Anette; Heegaard, Peter M H; Fomsgaard, Anders; Viuff, Birgitte; Hjulsager, Charlotte Kristiane

2013-09-18

The influenza A virus subtypes H1N1, H1N2 and H3N2 are the most prevalent subtypes in swine. In 2003, a reassorted H1N2 swine influenza virus (SIV) subtype appeared and became prevalent in Denmark. In the present study, the reassortant H1N2 subtype was characterised genetically and the infection dynamics compared to an "avian-like" H1N1 virus by an experimental infection study. Sequence analyses were performed of the H1N2 virus. Two groups of pigs were inoculated with the reassortant H1N2 virus and an "avian-like" H1N1 virus, respectively, followed by inoculation with the opposite subtype four weeks later. Measurements of HI antibodies and acute phase proteins were performed. Nasal virus excretion and virus load in lungs were determined by real-time RT-PCR. The phylogenetic analysis revealed that the reassorted H1N2 virus contained a European "avian-like" H1-gene and a European "swine-like" N2-gene, thus being genetically distinct from most H1N2 viruses circulating in Europe, but similar to viruses reported in 2009/2010 in Sweden and Italy. Sequence analyses of the internal genes revealed that the reassortment probably arose between circulating Danish "avian-like" H1N1 and H3N2 SIVs. Infected pigs developed cross-reactive antibodies, and increased levels of acute phase proteins after inoculations. Pigs inoculated with H1N2 exhibited nasal virus excretion for seven days, peaking day 1 after inoculation two days earlier than H1N1 infected pigs and at a six times higher level. The difference, however, was not statistically significant. Pigs euthanized on day 4 after inoculation, had a high virus load in all lung lobes. After the second inoculation, the nasal virus excretion was minimal. There were no clinical sign except elevated body temperature under the experimental conditions. The "avian-like" H1N2 subtype, which has been established in the Danish pig population at least since 2003, is a reassortant between circulating swine "avian-like" H1N1 and H3N2. The Danish

Genetic and biological characterisation of an avian-like H1N2 swine influenza virus generated by reassortment of circulating avian-like H1N1 and H3N2 subtypes in Denmark

DEFF Research Database (Denmark)

Trebbien, Ramona; Bragstad, Karoline; Larsen, Lars Erik

2013-01-01

BACKGROUND: The influenza A virus subtypes H1N1, H1N2 and H3N2 are the most prevalent subtypes in swine. In 2003, a reassorted H1N2 swine influenza virus (SIV) subtype appeared and became prevalent in Denmark. In the present study, the reassortant H1N2 subtype was characterised genetically...... and the infection dynamics compared to an “avian-like” H1N1 virus by an experimental infection study. METHODS: Sequence analyses were performed of the H1N2 virus. Two groups of pigs were inoculated with the reassortant H1N2 virus and an “avian-like” H1N1 virus, respectively, followed by inoculation...... with the opposite subtype four weeks later. Measurements of HI antibodies and acute phase proteins were performed. Nasal virus excretion and virus load in lungs were determined by real-time RT-PCR. RESULTS: The phylogenetic analysis revealed that the reassorted H1N2 virus contained a European “avian-like” H1-gene...

Avian Influenza A (H5N1)

Centers for Disease Control (CDC) Podcasts

In this podcast, CDC's Dr. Tim Uyeki discusses H5N1, a subtype of influenza A virus. This highly pathogenic H5N1 virus doesn't usually infect people, although some rare infections with H5N1 viruses have occurred in humans. We need to use a comprehensive strategy to prevent the spread of H5N1 virus among birds, including having human health and animal health work closely together.

Outbreak of influenza type A (H1N1 in Iporanga, São Paulo State, Brazil Epidemia de influenza A (H1N1 no Município de Iporanga, SP, Brasil

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Terezinha Maria de PAIVA

2001-12-01

Full Text Available From June to July 1999 an outbreak of acute respiratory illness occurred in the town of Iporanga. Out of a total of 4,837 inhabitants, 324 cases were notified to the Regional Surveillance Service. Influenza virus was isolated from 57.1% of the collected samples and 100% seroconversion to influenza A (H1N1 was obtained in 20 paired sera tested. The isolates were related to the A/Bayern/07/95 strain (H1N1. The percentages of cases notified during the outbreak were 28.4%, 29.0%, 20.7%, 6.2% and 15.7% in the age groups of 0-4, 5-9, 10-14, 15-19 and older than 20 years, respectively. The highest proportion of positives was observed among children younger than 14 years and no cases were notified in people older than 65 years, none of whom had been recently vaccinated against influenza. These findings suggest a significant vaccine protection against A/Bayern/7/95, the H1 component included in the 1997-98 influenza vaccine for elderly people. This viral strain is antigenically and genetically related to A/Beijing/262/95, the H1 component of the 1999 vaccine. Vaccines containing A/Beijing/262/95 (H1N1 stimulated post-immunization hemagglutination inhibition antibodies equivalent in frequency and titre to both A/Beijing/262/95-like and A/Bayern/7/95-like viruses. Thus, this investigation demonstrates the effectiveness of vaccination against influenza virus in the elderly.Durante os meses de junho e julho de 1999, foram notificados 324 casos de doença respiratória aguda no Município de Iporanga-SP. O isolamento do vírus da influenza do tipo A/Bayern/07/95 (H1N1 e a conversão sorológica para a estirpe viral (H1N1 foram de 57,1% e 100%, respectivamente. A porcentagem de casos com diagnóstico clínico notificados durante a epidemia foi de 28,4%, 29,0%, 20,7%, 6,2% e 15,7%, nas faixas etárias de 0-4, 5-9, 10-14, 15-19 anos e indivíduos acima de 20 anos de idade, respectivamente. Observou-se maior incidência da doença entre os indivíduos menores de

Large Scale Genome Analysis Shows that the Epitopes for Broadly Cross-Reactive Antibodies Are Predominant in the Pandemic 2009 Influenza Virus A H1N1 Strain

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Edgar E. Lara-Ramírez

2013-11-01

Full Text Available The past pandemic strain H1N1 (A (H1N1pdm09 has now become a common component of current seasonal influenza viruses. It has changed the pre-existing immunity of the human population to succeeding infections. In the present study, a total of 14,210 distinct sequences downloaded from National Center for Biotechnology Information (NCBI database were used for the analysis. The epitope compositions in A (H1N1pdm09, classic seasonal strains, swine strains as well as highly virulent avian strain H5N1, identified with the aid of the Immune Epitope DataBase (IEDB, were compared at genomic level. The result showed that A (H1N1 pdm09 contains the 90% of B-cell epitopes for broadly cross-reactive antibodies (EBCA, which is in consonance with the recent reports on the experimental identification of new epitopes or antibodies for this virus and the binding tests with influenza virus protein HA of different subtypes. Our analysis supports that high proportional EBCA depends on the epitope pattern of A (H1N1pdm09 virus. This study may be helpful for better understanding of A (H1N1pdm09 and the production of new influenza vaccines.

Microneedle Vaccination Elicits Superior Protection and Antibody Response over Intranasal Vaccination against Swine-Origin Influenza A (H1N1 in Mice.

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Ju-Hyung Shin

Full Text Available Influenza is one of the critical infectious diseases globally and vaccination has been considered as the best way to prevent. In this study, immunogenicity and protection efficacy between intranasal (IN and microneedle (MN vaccination was compared using inactivated swine-origin influenza A/H1N1 virus vaccine. Mice were vaccinated by MN or IN administration with 1 μg of inactivated H1N1 virus vaccine. Antigen-specific antibody responses and hemagglutination-inhibition (HI titers were measured in all immunized sera after immunization. Five weeks after an immunization, a lethal challenge was performed to evaluate the protective efficacy. Furthermore, mice were vaccinated by IN administration with higher dosages (> 1 μg, analyzed in the same manner, and compared with 1 μg-vaccine-coated MN. Significantly higher antigen-specific antibody responses and HI titer were measured in sera in MN group than those in IN group. While 100% protection, slight weight loss, and reduced viral replication were observed in MN group, 0% survival rate were observed in IN group. As vaccine dose for IN vaccination increased, MN-immunized sera showed much higher antigen-specific antibody responses and HI titer than other IN groups. In addition, protective immunity of 1 μg-MN group was similar to those of 20- and 40 μg-IN groups. We conclude that MN vaccination showed more potential immune response and protection than IN vaccination at the same vaccine dosage.

Influenza A (H1N1) pneumonia: HRCT findings

Energy Technology Data Exchange (ETDEWEB)

Amorim, Viviane Brandao; Rodrigues, Rosana Souza; Barreto, Miriam Menna; Marchiori, Edson, E-mail: edmarchiori@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Zanetti, Glaucia [Escola de Medicina de Petropolis, RJ (Brazil); Hochhegger, Bruno [Santa Casa de Misericordia de Porto Alegre, RS (Brazil)

2013-11-01

Objective: to describe aspects found on HRCT scans of the chest in patients infected with the influenza A (H1N1) virus. Methods: we retrospectively analyzed the HRCT scans of 71 patients (38 females and 33 males) with H1N1 infection, confirmed through laboratory tests, between July and September of 2009. The HRCT scans were interpreted by two thoracic radiologists independently, and in case of disagreement, the decisions were made by consensus. Results: the most common HRCT findings were ground-glass opacities (85%), consolidation (64%), or a combination of ground-glass opacities and consolidation (58%). Other findings were airspace nodules (25%), bronchial wall thickening (25%), interlobular septal thickening (21%), crazy-paving pattern (15%), perilobular pattern (3%), and air trapping (3%). The findings were frequently bilateral (89%), with a random distribution (68%). Pleural effusion, when observed, was typically minimal. No lymphadenopathy was identified. Conclusions: the most common findings were ground-glass opacities and consolidations, or a combination of both. Involvement was commonly bilateral with no axial or cranio caudal predominance in the distribution. Although the major tomographic findings in H1N1 infection are nonspecific, it is important to recognize such findings in order to include infection with the H1N1 virus in the differential diagnosis of respiratory symptoms. (author)

Protective Efficacy of Recombinant Turkey Herpes Virus (rHVT-H5) and Inactivated H5N1 Vaccines in Commercial Mulard Ducks against the Highly Pathogenic Avian Influenza (HPAI) H5N1 Clade 2.2.1 Virus.

Science.gov (United States)

Kilany, Walid H; Safwat, Marwa; Mohammed, Samy M; Salim, Abdullah; Fasina, Folorunso Oludayo; Fasanmi, Olubunmi G; Shalaby, Azhar G; Dauphin, Gwenaelle; Hassan, Mohammed K; Lubroth, Juan; Jobre, Yilma M

2016-01-01

In Egypt, ducks kept for commercial purposes constitute the second highest poultry population, at 150 million ducks/year. Hence, ducks play an important role in the introduction and transmission of avian influenza (AI) in the Egyptian poultry population. Attempts to control outbreaks include the use of vaccines, which have varying levels of efficacy and failure. To date, the effects of vaccine efficacy has rarely been determined in ducks. In this study, we evaluated the protective efficacy of a live recombinant vector vaccine based on a turkey Herpes Virus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAIV strain (A/Swan/Hungary/499/2006) (rHVT-H5) and a bivalent inactivated H5N1 vaccine prepared from clade 2.2.1 and 2.2.1.1 H5N1 seeds in Mulard ducks. A 0.3ml/dose subcutaneous injection of rHVT-H5 vaccine was administered to one-day-old ducklings (D1) and another 0.5ml/dose subcutaneous injection of the inactivated MEFLUVAC was administered at 7 days (D7). Four separate challenge experiments were conducted at Days 21, 28, 35 and 42, in which all the vaccinated ducks were challenged with 106EID50/duck of H5N1 HPAI virus (A/chicken/Egypt/128s/2012(H5N1) (clade 2.2.1) via intranasal inoculation. Maternal-derived antibody regression and post-vaccination antibody immune responses were monitored weekly. Ducks vaccinated at 21, 28, 35 and 42 days with the rHVT-H5 and MEFLUVAC vaccines were protected against mortality (80%, 80%, 90% and 90%) and (50%, 70%, 80% and 90%) respectively, against challenges with the H5N1 HPAI virus. The amount of viral shedding and shedding rates were lower in the rHVT-H5 vaccine groups than in the MEFLUVAC groups only in the first two challenge experiments. However, the non-vaccinated groups shed significantly more of the virus than the vaccinated groups. Both rHVT-H5 and MEFLUVAC provide early protection, and rHVT-H5 vaccine in particular provides protection against HPAI challenge.

Expression of innate immune genes, proteins and microRNAs in lung tissue of pigs infected experimentally with influenza virus (H1N2)

DEFF Research Database (Denmark)

Skovgaard, Kerstin; Cirera, Susanna; Vasby, Ditte

2013-01-01

This study aimed at providing a better understanding of the involvement of innate immune factors, including miRNA, in the local host response to influenza virus infection. Twenty pigs were challenged by influenza A virus subtype H1N2. Expression of microRNA (miRNA), mRNA and proteins were...... results suggest that, in addition to a wide range of innate immune factors, miRNAs may also be involved in controlling acute influenza infection in pigs....

Experimental infection of clade 1.1.2 (H5N1), clade 2.3.2.1c (H5N1) and clade 2.3.4.4 (H5N6) highly pathogenic avian influenza viruses in dogs.

Science.gov (United States)

Lyoo, K S; Na, W; Phan, L V; Yoon, S W; Yeom, M; Song, D; Jeong, D G

2017-12-01

Since the emergence of highly pathogenic avian influenza (HPAI) H5N1 in Asia, the haemagglutinin (HA) gene of this virus lineage has continued to evolve in avian populations, and H5N1 lineage viruses now circulate concurrently worldwide. Dogs may act as an intermediate host, increasing the potential for zoonotic transmission of influenza viruses. Virus transmission and pathologic changes in HPAI clade 1.1.2 (H5N1)-, 2.3.2.1c (H5N1)- and 2.3.4.4 (H5N6)-infected dogs were investigated. Mild respiratory signs and antibody response were shown in dogs intranasally infected with the viruses. Lung histopathology showed lesions that were associated with moderate interstitial pneumonia in the infected dogs. In this study, HPAI H5N6 virus replication in dogs was demonstrated for the first time. Dogs have been suspected as a "mixing vessel" for reassortments between avian and human influenza viruses to occur. The replication of these three subtypes of the H5 lineage of HPAI viruses in dogs suggests that dogs could serve as intermediate hosts for avian-human influenza virus reassortment if they are also co-infected with human influenza viruses. © 2017 Blackwell Verlag GmbH.

Involvement of the different lung compartments in the pathogenesis of pH1N1 influenza virus infection in ferrets.

Science.gov (United States)

Vidaña, Beatriz; Martínez, Jorge; Martorell, Jaime; Montoya, María; Córdoba, Lorena; Pérez, Mónica; Majó, Natàlia

2016-11-08

Severe cases after pH1N1 infection are consequence of interstitial pneumonia triggered by alveolar viral replication and an exacerbated host immune response, characterized by the up-regulation of pro-inflammatory cytokines and the influx of inflammatory leukocytes to the lungs. Different lung cell populations have been suggested as culprits in the unregulated innate immune responses observed in these cases. This study aims to clarify this question by studying the different induction of innate immune molecules by the distinct lung anatomic compartments (vascular, alveolar and bronchiolar) of ferrets intratracheally infected with a human pH1N1 viral isolate, by means of laser microdissection techniques. The obtained results were then analysed in relation to viral quantification in the different anatomic areas and the histopathological lesions observed. More severe lung lesions were observed at 24 h post infection (hpi) correlating with viral antigen detection in bronchiolar and alveolar epithelial cells. However, high levels of viral RNA were detected in all anatomic compartments throughout infection. Bronchiolar areas were the first source of IFN-α and most pro-inflammatory cytokines, through the activation of RIG-I. In contrast, vascular areas contributed with the highest induction of CCL2 and other pro-inflammatory cytokines, through the activation of TLR3.

Genetic structure of human A/H1N1 and A/H3N2 influenza virus on Corsica Island: phylogenetic analysis and vaccine strain match, 2006-2010.

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Alessandra Falchi

Full Text Available BACKGROUND: The aim of this study was to analyse the genetic patterns of Hemagglutinin (HA genes of influenza A strains circulating on Corsica Island during the 2006-2009 epidemic seasons and the 2009-2010 pandemic season. METHODS: Nasopharyngeal samples from 371 patients with influenza-like illness (ILI were collected by General Practitioners (GPs of the Sentinelles Network through a randomised selection routine. RESULTS: Phylogenetic analysis of HA revealed that A/H3N2 strains circulating on Corsica were closely related to the WHO recommended vaccine strains in each analyzed season (2006-2007 to 2008-2009. Seasonal Corsican influenza A/H1N1 isolated during the 2007-2008 season had drifted towards the A/Brisbane/59/2007 lineage, the A/H1N1 vaccine strain for the 2008-2009 season. The A/H1N1 2009 (A/H1N1pdm strains isolated on Corsica Island were characterized by the S220T mutation specific to clade 7 isolates. It should be noted that Corsican isolates formed a separate sub-clade of clade 7 as a consequence of the presence of the fixed substitution D222E. The percentages of the perfect match vaccine efficacy, estimated by using the p(epitope model, against influenza viruses circulating on Corsica Island varied substantially across the four seasons analyzed, and tend to be highest for A/H1N1 compared with A/H3N2 vaccines, suggesting that cross-immunity seems to be stronger for the H1 HA gene. CONCLUSION: The molecular analysis of the HA gene of influenza viruses that circulated on Corsica Island between 2006-2010 showed for each season the presence of a dominant lineage characterized by at least one fixed mutation. The A/H3N2 and A/H1N1pdm isolates were characterized by multiples fixation at antigenic sites. The fixation of specific mutations at each outbreak could be explained by the combination of a neutral phenomenon and a founder effect, favoring the presence of a dominant lineage in a closed environment such as Corsica Island.

Outbreak of pandemic influenza A/H1N1 2009 in Nepal.

Science.gov (United States)

Adhikari, Bal Ram; Shakya, Geeta; Upadhyay, Bishnu Prasad; Prakash Kc, Khagendra; Shrestha, Sirjana Devi; Dhungana, Guna Raj

2011-03-23

The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1) 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009. Out of 609 collected samples, 302 (49.6%) were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3%) were positive for Pandemic influenza A/H1N1 and 130 (21.3%) were Seasonal influenza A. Most of the pandemic cases (53%) were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1)v type. The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1)v type.

Outbreak of pandemic influenza A/H1N1 2009 in Nepal

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Shrestha Sirjana

2011-03-01

Full Text Available Abstract Background The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009. Results Out of 609 collected samples, 302 (49.6% were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3% were positive for Pandemic influenza A/H1N1 and 130 (21.3% were Seasonal influenza A. Most of the pandemic cases (53% were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1v type. Conclusion The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1v type.

Global Alfvén eigenmodes in the H-1 heliac

Science.gov (United States)

Hole, M. J.; Blackwell, B. D.; Bowden, G.; Cole, M.; Könies, A.; Michael, C.; Zhao, F.; Haskey, S. R.

2017-12-01

Recent upgrades in H-1 power supplies have enabled the operation of the H-1 experiment at higher heating powers than previously attainable. A heating power scan in mixed hydrogen/helium plasmas reveals a change in mode activity with increasing heating power. At low power (magnetic field. They reveal drive is possible with a small ({n}f/{n}0 300 {eV}. Local linear growth rate scans are also complemented with global calculations from CKA and EUTERPE. These qualitatively confirm the findings from the LGRO study, and show that the inclusion of finite Larmor radius effects can reduce the growth rate by a factor of up to ten, and increases the marginal stability fast ion temperature by a factor of two. Finally, a study of damping of the global mode with the thermal plasma is conducted, computing continuum damping , and the damping arising from finite Larmor radius and parallel electric fields (via resistivity). We find that continuum damping is of order 0.1% for the configuration studied. A similar calculation in the cylindrical plasma model produces a frequency 35% higher and a damping 30% of the three-dimensional result: this confirms the importance of strong magnetic shaping to the frequency and damping. The inclusion of resistivity lifts the damping to γ /ω =-0.189. Such large damping is consistent with experimental observations that in absence of drive the mode decays rapidly (∼0.1 ms).

Genetic drift evolution under vaccination pressure among H5N1 Egyptian isolates

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Afifi Manal A

2011-06-01

Full Text Available Background The highly pathogenic H5N1 is a major avian pathogen that intensively affects the poultry industry in Egypt even in spite of the adoption of vaccination strategy. Antigenic drift is among the strategies the influenza virus uses to escape the immune system that might develop due to the pressure of extensive vaccination. H5N1 mutates in an intensified manner and is considered a potential candidate for the possible next pandemic with all the catastrophic consequences such an eventuality will entail. Methods H5N1 was isolated from the pooled organ samples of four different affected flocks in specific pathogen free embryonated chicken eggs (SPF-ECE. A reverse transcriptase polymerase chain reaction (RT-PCR was performed to the haemagglutingin and neuraminidase. Sequencing of the full length haemagglutingin was performed. Sequence analyses of the isolated strains were performed and compared to all available H5N1 from Egyptian human and avian strains in the flu database. Changes in the different amino acid that may be related to virus virulence, receptor affinity and epitope configuration were assigned and matched with all available Egyptian strains in the flu database. Results One out of the four strains was found to be related to the B2 Egyptian lineage, 2 were related to A1 lineage and the 4th was related to A2 lineage. Comparing data obtained from the current study by other available Egyptian H5N1 sequences remarkably demonstrates that amino acid changes in the immune escape variants are remarkably restricted to a limited number of locations on the HA molecule during antigenic drift. Molecular diversity in the HA gene, in relevance to different epitopes, were not found to follow a regular trend, suggesting abrupt cumulative sequence mutations. However a number of amino acids were found to be subjected to high mutation pressure. Conclusion The current data provides a comprehensive view of HA gene evolution among H5N1 subtype viruses in

Fitness of Pandemic H1N1 and Seasonal influenza A viruses during Co-infection: Evidence of competitive advantage of pandemic H1N1 influenza versus seasonal influenza.

Science.gov (United States)

Perez, Daniel Roberto; Sorrell, Erin; Angel, Matthew; Ye, Jianqiang; Hickman, Danielle; Pena, Lindomar; Ramirez-Nieto, Gloria; Kimble, Brian; Araya, Yonas

2009-08-24

On June 11, 2009 the World Health Organization (WHO) declared a new H1N1 influenza pandemic. This pandemic strain is as transmissible as seasonal H1N1 and H3N2 influenza A viruses. Major concerns facing this pandemic are whether the new virus will replace, co-circulate and/or reassort with seasonal H1N1 and/or H3N2 human strains. Using the ferret model, we investigated which of these three possibilities were most likely favored. Our studies showed that the current pandemic virus is more transmissible than, and has a biological advantage over, prototypical seasonal H1 or H3 strains.

Pandemic influenza A (H1N1)

African Journals Online (AJOL)

... in Port Shepstone, South Africa. Introduction. Influenza A (H1N1) 2009 'swine flu' variant is currently a global pandemic.1 The infection associated with this virus is usually a mild, self-limiting illness. However, it may progress to severe pneumonia requiring intensive care unit (ICU) therapy in 31% of patients.2 This may.

A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus

OpenAIRE

Kang, Xiao-ping; Jiang, Tao; Li, Yong-qiang; Lin, Fang; Liu, Hong; Chang, Guo-hui; Zhu, Qing-yu; Qin, E-de; Qin, Cheng-feng; Yang, Yin-hui

2010-01-01

Abstract A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009) influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose) for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same a...

Avian Influenza A (H5N1)

Centers for Disease Control (CDC) Podcasts

2009-05-27

In this podcast, CDC's Dr. Tim Uyeki discusses H5N1, a subtype of influenza A virus. This highly pathogenic H5N1 virus doesn't usually infect people, although some rare infections with H5N1 viruses have occurred in humans. We need to use a comprehensive strategy to prevent the spread of H5N1 virus among birds, including having human health and animal health work closely together.  Created: 5/27/2009 by Emerging Infectious Diseases.   Date Released: 5/27/2009.

Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies.

Science.gov (United States)

Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse

2015-01-01

In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4(+) T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158.

IFN-λ and microRNAs are important modulators of the pulmonary innate immune response against influenza A (H1N2) infection in pigs

DEFF Research Database (Denmark)

Brogaard, Louise; Larsen, Lars E.; Heegaard, Peter Mikael Helweg

2018-01-01

the expression of miRNAs and protein coding genes in the lungs of pigs 1, 3, and 14 days after challenge with swine IAV (H1N2). Through RT-qPCR we observed a 400-fold relative increase in IFN-lambda 3 gene expression on day 1 after challenge, and a strong interferon-mediated antiviral response was observed......The innate immune system is paramount in the response to and clearance of influenza A virus (IAV) infection in non-immune individuals. Known factors include type I and III interferons and antiviral pathogen recognition receptors, and the cascades of antiviral and pro- and anti-inflammatory gene...

Mucosal and Systemic Immune Responses to Influenza H7N9 Antigen HA1-2 Co-Delivered Intranasally with Flagellin or Polyethyleneimine in Mice and Chickens.

Science.gov (United States)

Song, Li; Xiong, Dan; Song, Hongqin; Wu, Lili; Zhang, Meihua; Kang, Xilong; Pan, Zhiming; Jiao, Xinan

2017-01-01

Consecutive cases of human infection with H7N9 influenza viruses since 2013 in China have prompted efforts to develop an effective treatment. Subunit vaccines introduced by intranasal administration can block an infection at its primary site; flagellin (fliC) and polyethyleneimine (PEI) have been shown to be potent adjuvants. We previously generated the hemagglutinin (HA)1-2-fliC fusion protein consisting of the globular head domain (HA1-2; amino acids 62-284) of HA fused with Salmonella typhimurium fliC. In the present study, we investigated its effectiveness of both flagellin and PEI as mucosal adjuvants for the H7N9 influenza subunit vaccine. Mice immunized intranasally with HA1-2-fliC and HA1-2-PEI showed higher HA1-2-specific immunoglobulin (Ig)G and IgA titers in serum, nasal wash, and bronchial alveolar lavage fluid. Moreover, splenocyte activation and proliferation and the number of HA1-2-specific interferon (IFN)-γ- and interleukin (IL)-4-producing splenocytes were markedly increased in the fliC and PEI groups; in the latter, there were more cells secreting IL-4 than IFN-γ, suggesting that fliC induced T helper type (Th)1 and Th2 immune responses, and PEI induced Th2-biased responses, consistent with the serum antibody isotype pattern (IgG1/IgG2a ratio). Furthermore, virus challenge was performed in a chicken model. The results showed that chickens receiving fliC and PEI adjuvant vaccine exhibited robust immune responses leading to a significant reduction in viral loads of throat and cloaca compared to chickens receiving only HA1-2. These findings provide a basis for the development of H7N9 influenza HA1-2 mucosal subunit vaccines.

A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus

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Qin E-de

2010-06-01

Full Text Available Abstract A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009 influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same as that of each single-target RT-PCR for pandemic H1N1 and even more sensitive for H5N1 with the same primers and probes. No cross reactivity of detecting other subtype influenza viruses or respiratory tract viruses was observed. Two hundred and thirty-six clinical specimens were tested by comparing with single real-time RT-PCR and result from the duplex assay was 100% consistent with the results of single real-time RT-PCR and sequence analysis.

Understanding the cross-resistance of oseltamivir to H1N1 and H5N1 influenza A neuraminidase mutations using multidimensional computational analyses

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Singh A

2015-07-01

Full Text Available Ashona Singh, Mahmoud E Soliman School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, South Africa Abstract: This study embarks on a comprehensive description of the conformational contributions to resistance of neuraminidase (N1 in H1N1 and H5N1 to oseltamivir, using comparative multiple molecular dynamic simulations. The available data with regard to elucidation of the mechanism of resistance as a result of mutations in H1N1 and H5N1 neuraminidases is not well established. Enhanced post-dynamic analysis, such as principal component analysis, solvent accessible surface area, free binding energy calculations, and radius of gyration were performed to gain a precise insight into the binding mode and origin of resistance of oseltamivir in H1N1 and H5N1 mutants. Three significant features reflecting resistance in the presence of mutations H274Y and I222K, of the protein complexed with the inhibitor are: reduced flexibility of the a-carbon backbone; an improved ΔEele of ~15 (kcal/mol for H1N1 coupled with an increase in ΔGsol­ (~13 kcal/mol from wild-type to mutation; a low binding affinity in comparison with the wild-type of ~2 (kcal/mol and ~7 (kcal/mol with respect to each mutation for the H5N1 systems; and reduced hydrophobicity of the overall surface structure due to an impaired hydrogen bonding network. We believe the results of this study will ultimately provide a useful insight into the structural landscape of neuraminidase-associated binding of oseltamivir. Furthermore, the results can be used in the design and development of potent inhibitors of neuraminidases. Keywords: neuraminidase, molecular dynamics, resistance, mutation, binding free energy

An analysis of 332 fatalities infected with pandemic 2009 influenza A (H1N1 in Argentina.

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Ana M Balanzat

Full Text Available The apparent high number of deaths in Argentina during the 2009 pandemic led to concern that the influenza A H1N1pdm disease was different there. We report the characteristics and risk factors for influenza A H1N1pdm fatalities.We identified laboratory-confirmed influenza A H1N1pdm fatalities occurring during June-July 2009. Physicians abstracted data on age, sex, time of onset of illness, medical history, clinical presentation at admission, laboratory, treatment, and outcomes using standardize questionnaires. We explored the characteristics of fatalities according to their age and risk group.Of 332 influenza A H1N1pdm fatalities, 226 (68% were among persons aged <50 years. Acute respiratory failure was the leading cause of death. Of all cases, 249 (75% had at least one comorbidity as defined by Advisory Committee on Immunization Practices. Obesity was reported in 32% with data and chronic pulmonary disease in 28%. Among the 40 deaths in children aged <5 years, chronic pulmonary disease (42% and neonatal pathologies (35% were the most common co-morbidities. Twenty (6% fatalities were among pregnant or postpartum women of which only 47% had diagnosed co-morbidities. Only 13% of patients received antiviral treatment within 48 hours of symptom onset. None of children aged <5 years or the pregnant women received antivirals within 48 h of symptom onset. As the pandemic progressed, the time from symptom-onset to medical care and to antiviral treatment decreased significantly among case-patients who subsequently died (p<0.001.Persons with co-morbidities, pregnant and who received antivirals late were over-represented among influenza A H1N1pdm deaths in Argentina, though timeliness of antiviral treatment improved during the pandemic.