Influenza A (H1N1)pnd09 Vaccination of Pregnant Women and Immunological Consequences for Their Offspring

DEFF Research Database (Denmark)

Bischoff, Anne Louise

2013-01-01

against H1N1pnd09 according to the EMEA criteria with a HI titre of 40 or greater. Women receiving the non-adjuvanted vaccine had significantly fewer local reactions but similar rates of systemic reactions as women receiving the adjuvanted vaccine. There were no reports of serious adverse events in any......Pregnant women experience increased influenza related morbidity and mortality during seasonal influenza epidemics, and even graver outcomes during influenza pandemics. Thus, even though the huge amount of data on clinical efficacy and effectiveness of influenza vaccine in pregnant women......, there is limited information on the details of the immunological responses to influenza immunization in pregnant versus non-pregnant. We had the unique opportunity to study the H1N1pnd09 vaccination of pregnant and non-pregnant women in our unselected, prospective, clinical pregnancy-cohort: the Copenhagen...

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.

Adaptation of high-growth influenza H5N1 vaccine virus in Vero cells: implications for pandemic preparedness.

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Yu-Fen Tseng

Full Text Available Current egg-based influenza vaccine production technology can't promptly meet the global demand during an influenza pandemic as shown in the 2009 H1N1 pandemic. Moreover, its manufacturing capacity would be vulnerable during pandemics caused by highly pathogenic avian influenza viruses. Therefore, vaccine production using mammalian cell technology is becoming attractive. Current influenza H5N1 vaccine strain (NIBRG-14, a reassortant virus between A/Vietnam/1194/2004 (H5N1 virus and egg-adapted high-growth A/PR/8/1934 virus, could grow efficiently in eggs and MDCK cells but not Vero cells which is the most popular cell line for manufacturing human vaccines. After serial passages and plaque purifications of the NIBRG-14 vaccine virus in Vero cells, one high-growth virus strain (Vero-15 was generated and can grow over 10(8 TCID(50/ml. In conclusion, one high-growth H5N1 vaccine virus was generated in Vero cells, which can be used to manufacture influenza H5N1 vaccines and prepare reassortant vaccine viruses for other influenza A subtypes.

Efficacy of a pandemic (H1N1) 2009 virus vaccine in pigs against the pandemic influenza virus is superior to commercially available swine influenza vaccines.

NARCIS (Netherlands)

Loeffen, W.L.A.; Stockhofe-Zurwieden, N.; Weesendorp, E.; Zoelen-Bos, van D.J.; Heutink, R.; Quak, J.; Goovaerts, D.; Heldens, J.; Maas, H.A.; Moormann, R.J.M.; Koch, G.

2011-01-01

In April 2009 a new influenza A/H1N1 strain, currently named “pandemic (H1N1) influenza 2009¿ (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to

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.

Relative Efficacy of AS03-Adjuvanted Pandemic Influenza A(H1N1) Vaccine in Children: Results of a Controlled, Randomized Efficacy Trial

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Nolan, Terry; Roy-Ghanta, Sumita; Montellano, May; Weckx, Lily; Ulloa-Gutierrez, Rolando; Lazcano-Ponce, Eduardo; Kerdpanich, Angkool; Safadi, Marco Aurélio Palazzi; Cruz-Valdez, Aurelio; Litao, Sandra; Lim, Fong Seng; de Los Santos, Abiel Mascareñas; Weber, Miguel Angel Rodriguez; Tinoco, Juan-Carlos; Mezerville, Marcela Hernandez-de; Faingezicht, Idis; Kosuwon, Pensri; Lopez, Pio; Borja-Tabora, Charissa; Li, Ping; Durviaux, Serge; Fries, Louis; Dubin, Gary; Breuer, Thomas; Innis, Bruce L.; Vaughn, David W.

2014-01-01

Background. The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010–2011. Methods. A total of 6145 children were randomly assigned at a ratio of 1:1:1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed. Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%–93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group. Conclusion. The 4–8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661. PMID:24652494

Patient reported outcome data following influenza A (H1N1p vaccination in the 2009–2010 season: web-based and telephone evaluation

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Wade AG

2011-10-01

Full Text Available Alan G Wade1, Gordon M Crawford1, Neil Pumford1, Alex McConnachie21Patients Direct, 3 Todd Campus, Glasgow, UK; 2Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UKBackground: There has been worldwide interest in the safety of the pandemic influenza A (H1N1p vaccines, although limited data are available from the vaccine recipients’ perspective. This evaluation was designed to collect data from people who had received an influenza vaccination during the 2009–2010 season using a web-based data collection tool supplemented by telephone reporting (PROBE.Methods: People scheduled to receive the influenza A (H1N1p or seasonal influenza vaccines were recruited through media advertising and campaigns throughout the West of Scotland. Vaccine recipients participated in the evaluation by answering demographic and side effect questions using PROBE methodology on the day of the immunization, after 3 days, 8 days, 6 weeks, 12 weeks, and 26 weeks.Results: A total of 1103 vaccine recipients including 134 young children (0–4 years participated in the evaluation; 694 (63% received H1N1p vaccine only, 135 (12% seasonal vaccine only, 224 (20% both H1N1p and seasonal vaccines, and 50 (5% received H1N1p or seasonal vaccine with a non-influenza vaccine (eg, travel or pneumococcal. Overall, 42% of recipients reported experiencing a side effect after their baseline vaccination; the most commonly reported were general and arm side effects (>20%. Injection site discomfort/pain and flu-like symptoms were reported by 57% and 24% of recipients, respectively. A significantly higher proportion of the 960 H1N1p vaccine recipients experienced a side effect (44% vs 27%, P < 0.001 or injection site discomfort/pain (61% vs 26%, P < 0.001 than those receiving seasonal influenza vaccines. Female sex and H1N1p vaccination were associated with a significantly higher risk of injection site discomfort/pain, whereas the 70+ age group was associated with a

Narcolepsy: Association with H1N1 Infection and Vaccination

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Ji Hyun Song

2016-12-01

Full Text Available Epidemiological studies have demonstrated an association between H1N1 influenza infection and vaccinations. This article reviews the various studies, and suggests the biological mechanisms explaining why and how H1N1 influenza infection or vaccine stimulates the autoimmune response, thereby resulting in narcolepsy. Among the vaccines, the effect of Pandemrix was scrutinized more than other vaccines, due to its higher association with an increase of narcolepsy onset. The consequences of using other vaccines which contain same or different adjuvants as Pandemrix, were also analyzed.

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

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 A H1N1pdm09 Virus and Severe Outcomes: A Reason for Broader Vaccination in Non-Elderly, At-Risk People.

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Elisa Minchole

Full Text Available Recent pandemics of influenza A H1N1pdm09 virus have caused severe illness, especially in young people. Very few studies on influenza A H1N1pdm09 in post-pandemic periods exist, and there is no information on the severity of both seasonal influenza A(H1N1 and A(H3N2 from the same season, adjusting for potential confounders, including vaccine.We performed a retrospective observational study of adults hospitalized during the 2014 season with influenza A(H1N1 or A(H3N2. All patients underwent the same diagnostic and therapeutic protocol in a single hospital, including early Oseltamivir therapy. We included 234 patients: 146 (62.4% influenza A(H1N1 and 88 (37.6% A(H3N2. A(H1N1 patients were younger (p<0.01, developed more pneumonia (p<0.01, respiratory complications (p = 0.015, ARDS (p = 0.047, and septic shock (p = 0.049, were more frequently admitted to the ICU (p = 0.022, required IMV (p = 0.049, and were less frequently vaccinated (p = 0.008. After adjusting for age, comorbidities, time from onset of illness, and vaccine status, influenza A(H1N1 (OR, 2.525, coinfection (OR, 2.821, and no vaccination (OR, 3.086 were independent risk factors for severe disease.Hospitalized patients with influenza A(H1N1 were more than twice as likely to have severe influenza. They were younger and most had not received the vaccine. Our findings suggest that seasonal influenza A(H1N1 maintains some features of pandemic viruses, and recommend wider use of vaccination in younger adult high-risk patients.

International collaboration to assess the risk of Guillain Barré Syndrome following Influenza A (H1N1) 2009 monovalent vaccines.

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Dodd, Caitlin N; Romio, Silvana A; Black, Steven; Vellozzi, Claudia; Andrews, Nick; Sturkenboom, Miriam; Zuber, Patrick; Hua, Wei; Bonhoeffer, Jan; Buttery, Jim; Crawford, Nigel; Deceuninck, Genevieve; de Vries, Corinne; De Wals, Philippe; Gutierrez-Gimeno, M Victoria; Heijbel, Harald; Hughes, Hayley; Hur, Kwan; Hviid, Anders; Kelman, Jeffrey; Kilpi, Tehri; Chuang, S K; Macartney, Kristine; Rett, Melisa; Lopez-Callada, Vesta Richardson; Salmon, Daniel; Gimenez-Sanchez, Francisco; Sanz, Nuria; Silverman, Barbara; Storsaeter, Jann; Thirugnanam, Umapathi; van der Maas, Nicoline; Yih, Katherine; Zhang, Tao; Izurieta, Hector

2013-09-13

The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barré syndrome (GBS), which has been an influenza vaccine safety concern since the swine flu pandemic of 1976, using a common protocol among high and middle-income countries. The primary objective of this project was to demonstrate the feasibility and utility of global collaboration in the assessment of vaccine safety, including countries both with and without an established infrastructure for vaccine active safety surveillance. A second objective, included a priori, was to assess the risk of GBS following pH1N1 vaccination. The primary analysis used the self-controlled case series (SCCS) design to estimate the relative incidence (RI) of GBS in the 42 days following vaccination with pH1N1 vaccine in a pooled analysis across databases and in analysis using a meta-analytic approach. We found a relative incidence of GBS of 2.42 (95% CI 1.58-3.72) in the 42 days following exposure to pH1N1 vaccine in analysis of pooled data and 2.09 (95% CI 1.28-3.42) using the meta-analytic approach. This study demonstrates that international collaboration to evaluate serious outcomes using a common protocol is feasible. The significance and consistency of our findings support a conclusion of an association between 2009 H1N1 vaccination and GBS. Given the rarity of the event the relative incidence found does not provide evidence in contradiction to international recommendations for the continued use of influenza vaccines. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cold-adapted influenza and recombinant adenovirus vaccines induce cross-protective immunity against pH1N1 challenge in mice.

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Mark R Soboleski

Full Text Available The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1 highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus.BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca influenza viruses from 1977 or recombinant adenoviruses (rAd expressing 1934 nucleoprotein (NP and consensus matrix 2 (M2 (NP+M2-rAd. Antibodies against the M2 ectodomain (M2e were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus.Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic.

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.

Conocimientos, actitudes y prácticas sobre la influenza A(H1N1 2009 y la vacunación contra influenza pandémica: resultados de una encuesta poblacional Knowledge, attitudes and practices about influenza A(H1N1 2009, and influenza vaccine in Mexico: results of a population survey

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María Eugenia Jiménez-Corona

2012-12-01

Full Text Available OBJETIVO: Evaluar conocimientos, actitudes y prácticas respecto a la pandemia de influenza, con especial énfasis en la vacuna contra influenza estacional y pandémica. MATERIAL Y MÉTODOS: Estudio transversal con muestreo polietápico probabilístico, realizado durante diciembre de 2009 en residentes mayores de 18 años de la Ciudad de México (y área metropolitana, Monterrey, Guadalajara y Mérida. RESULTADOS: Se incluyeron 1 600 sujetos (48.9% masculino; 34% había recibido vacuna contra influenza estacional en años pasados, 90.6% estaba dispuesto a recibir la vacuna contra A(H1N1. La principal causa de rechazo a la vacunación fue no confiar en la vacuna (46.5%. Principales medidas preventivas identificadas por los encuestados: lavado de manos (47.5%, vacuna contra A(H1N1 (28% y etiqueta respiratoria (19.4%. El nivel escolar (1.7, p=0.006 y edad (1.02, pOBJECTIVE: To assess knowledge, attitudes and practices regarding influenza pandemic, with special emphasis on issues related to influenza vaccine, seasonal and pandemic. MATERIALS AND METHODS: Cross-sectional study, probabilistic multistage sampling in patients over 18 years, residents of Mexico City (and metropolitan area, Monterrey, Guadalajara and Merida in December 2009. RESULTS: A total of 1.600 subjects (48.9% male were interviewed, 34% had previously received seasonal flu vaccine, 90.6% were willing to be vaccinated against A(H1N1, 46.5% of those who would not receive the vaccine was because they did not trust A (H1N1, 68% considered influenza A (H1N1 as a risk for their family. Hand washing was the preventive measure most commonly reported (47.5%, secondly influenza vaccine (28%. Schooling (1.7, p=0.006 and age (1.02, p<0.001 influence rejection to get vaccine. 82.9% of respondents rate the federal government's management as good or very good. CONCLUSIONS: There was a high acceptance rate for the pandemic influenza vaccine in Mexico when compared to similar studies in other

Acceptance of a vaccine against novel influenza A (H1N1) virus among health care workers in two major cities in Mexico.

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Esteves-Jaramillo, Alejandra; Omer, Saad B; Gonzalez-Diaz, Esteban; Salmon, Daniel A; Hixson, Brooke; Navarro, Francisco; Kawa-Karasik, Simon; Frew, Paula; Morfin-Otero, Rayo; Rodriguez-Noriega, Eduardo; Ramirez, Ylean; Rosas, Araceli; Acosta, Edgar; Varela-Badillo, Vianey; Del Rio, Carlos

2009-11-01

Further cases of novel influenza A (H1N1) outbreak are expected in the coming months. Vaccination has been proven to be essential to control a pandemic of influenza; therefore, considerable efforts and resources have been devoted to develop a vaccine against the influenza A (H1N1) virus. With the current availability of the vaccine, it will be important to immunize as many people as possible. However, previous data with seasonal influenza vaccines have shown that there are multiple barriers related to perceptions and attitudes of the population that influence vaccine use. The aim of the study was to evaluate the acceptance of a newly developed vaccine against pandemic (H1N1) 2009 influenza A among healthcare workers (HCW) in Mexico. We conducted a cross-sectional study among HCW in three hospitals in the two largest cities in Mexico-Mexico City and Guadalajara-between June and September 2009. A total of 1097 HCW participated in the survey. Overall, 80% (n = 880) intended to accept the H1N1 pandemic vaccine and 71.6% (n = 786) reported they would recommend the vaccine to their patients. Doctors were more likely to accept and recommend the vaccine than nurses. HCWs who intend to be immunized will be more likely to do so if they know that the vaccine is safe and effective. Knowledge of the willingness to accept the vaccine can be used to plan strategies that will effectively respond to the needs of the population studied, reducing the health and economic impact of novel influenza A (H1N1) virus.

Lessons from pandemic influenza A(H1N1): the research-based vaccine industry's perspective.

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Abelin, Atika; Colegate, Tony; Gardner, Stephen; Hehme, Norbert; Palache, Abraham

2011-02-01

As A(H1N1) influenza enters the post-pandemic phase, health authorities around the world are reviewing the response to the pandemic. To ensure this process enhances future preparations, it is essential that perspectives are included from all relevant stakeholders, including vaccine manufacturers. This paper outlines the contribution of R&D-based influenza vaccine producers to the pandemic response, and explores lessons that can be learned to improve future preparedness. The emergence of 2009 A(H1N1) influenza led to unprecedented collaboration between global health authorities, scientists and manufacturers, resulting in the most comprehensive pandemic response ever undertaken, with a number of vaccines approved for use three months after the pandemic declaration. This response was only possible because of the extensive preparations undertaken during the last decade. During this period, manufacturers greatly increased influenza vaccine production capacity, and estimates suggest a further doubling of capacity by 2014. Producers also introduced cell-culture technology, while adjuvant and whole virion technologies significantly reduced pandemic vaccine antigen content. This substantially increased pandemic vaccine production capacity, which in July 2009 WHO estimated reached 4.9 billion doses per annum. Manufacturers also worked with health authorities to establish risk management plans for robust vaccine surveillance during the pandemic. Individual producers pledged significant donations of vaccine doses and tiered-pricing approaches for developing country supply. Based on the pandemic experience, a number of improvements would strengthen future preparedness. Technical improvements to rapidly select optimal vaccine viruses, and processes to speed up vaccine standardization, could accelerate and extend vaccine availability. Establishing vaccine supply agreements beforehand would avoid the need for complex discussions during a period of intense time pressure. Enhancing

An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus.

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Leung, Ho-Chuen; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Zhao, Han-Jun; Cheung, Chung-Yan; Ng, Fai; Huang, Jian-Dong; Zheng, Bo-Jian

2015-04-01

In March 2013, a patient infected with a novel avian influenza A H7N9 virus was reported in China. Since then, there have been 458 confirmed infection cases and 177 deaths. The virus contains several human-adapted markers, indicating that H7N9 has pandemic potential. The outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. Previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of the H5N1 virus (H5N1-M2e) could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection with the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20, and 21 between M2e of H5N1 and H7N9, H5N1-M2e vaccination with either Freund's adjuvant or the Sigma adjuvant system (SAS) induced a high level of anti-M2e antibody, which cross-reacted with H7N9-M2e peptide. A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of the H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections. Therefore, this vaccine may be an ideal candidate for developing a universal vaccine to prevent the reemergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus.

International collaboration to assess the risk of Guillain Barre Syndrome following Influenza A (H1N1) 2009 monovalent vaccines

NARCIS (Netherlands)

Dodd, Caitlin N.; Romio, Silvana A.; Black, Steven; Vellozzi, Claudia; Andrews, Nick; Sturkenboom, Miriam; Zuber, Patrick; Hua, Wei; Bonhoeffer, Jan; Buttery, Jim; Crawford, Nigel; Deceuninck, Genevieve; de Vries, Corinne; De Wals, Philippe; Gutierrez-Gimeno, M. Victoria; Heijbel, Harald; Hughes, Hayley; Hur, Kwan; Hviid, Anders; Kelman, Jeffrey; Kilpi, Tehri; Chuang, S. K.; Macartney, Kristine; Rett, Melisa; Lopez-Callada, Vesta Richardson; Salmon, Daniel; Sanchez, Francisco Gimenez; Sanz, Nuria; Silverman, Barbara; Storsaeter, Jann; Thirugnanam, Umapathi; van der Maas, Nicoline; Yih, Katherine; Zhang, Tao; Izurieta, Hector

2013-01-01

Background: The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barre syndrome (GBS), which has been an

Economic evaluation of the vaccination program against seasonal and pandemic A/H1N1 influenza among customs officers in Greece.

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Mamma, Maria; Spandidos, Demetrios A

2013-01-01

Health policies from many countries recommend influenza vaccination of "high-priority" professional groups, including customs officers. Our aim was to estimate the economic impact of the vaccination program against influenza among customs officers in Greece during the 2009/2010 period. We developed a decision analytical computational simulation model including dynamic transmission elements that estimated the economic impact of various scenarios with different attack rates, symptomatic percentages and vaccination participation among customs officers. We also assessed in real-time the economic impact of the national 2009/2010 campaign against seasonal and pandemic A/H1N1 influenza. Implementing a seasonal and pandemic A/H1N1 influenza vaccination program among customs officers in Greece with a participation rate of 30%, influenza vaccination was not cost-saving in any of the studied influenza scenarios. When the participation rate reached 100%, the program was cost-saving, when the influenza attack rate was 30% and the symptomatic rate 65%. The real-time estimated mean net cost-benefit value in 2009/2010 period was -7.3 euros/custom officer. With different clinical scenarios, providing a vaccination program against seasonal and pandemic A/H1N1 influenza can incur a substantial net benefit for customs offices. However, the size of the benefit strongly depends upon the attack rate of influenza, the symptomatic rate as well as the participation rate of the customs officers in the program. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Protection against H5N1 Highly Pathogenic Avian and Pandemic (H1N1) 2009 Influenza Virus Infection in Cynomolgus Monkeys by an Inactivated H5N1 Whole Particle Vaccine

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Nakayama, Misako; Shichinohe, Shintaro; Itoh, Yasushi; Ishigaki, Hirohito; Kitano, Mitsutaka; Arikata, Masahiko; Pham, Van Loi; Ishida, Hideaki; Kitagawa, Naoko; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Ichikawa, Takaya; Tsuchiya, Hideaki; Nakamura, Shinichiro; Le, Quynh Mai; Ito, Mutsumi; Kawaoka, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa

2013-01-01

H5N1 highly pathogenic avian influenza virus (HPAIV) infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3), in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1) 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3. PMID:24376571

Protection against H5N1 highly pathogenic avian and pandemic (H1N1 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine.

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Misako Nakayama

Full Text Available H5N1 highly pathogenic avian influenza virus (HPAIV infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3, in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3.

Cold-Adapted Influenza and Recombinant Adenovirus Vaccines Induce Cross-Protective Immunity against pH1N1 Challenge in Mice

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Soboleski, Mark R.; Gabbard, Jon D.; Price, Graeme E.; Misplon, Julia A.; Lo, Chia-Yun; Perez, Daniel R.; Ye, Jianqiang; Tompkins, S. Mark; Epstein, Suzanne L.

2011-01-01

Background The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1) highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus. Methodology/Principal Findings BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca) influenza viruses from 1977 or recombinant adenoviruses (rAd) expressing 1934 nucleoprotein (NP) and consensus matrix 2 (M2) (NP+M2-rAd). Antibodies against the M2 ectodomain (M2e) were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus. Conclusion/Significance Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic. PMID:21789196

Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets

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Mills, Kimberly L; Jin, Hong; Duke, Greg; Lu, Bin; Luke, Catherine J; Murphy, Brian; Swayne, David E; Kemble, George; Subbarao, Kanta

2006-01-01

Background Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. Methods and Findings Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 106 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. Conclusions The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans. PMID:16968127

Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets.

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Amorsolo L Suguitan

2006-09-01

Full Text Available Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic.Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA and a wild-type (wt N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2, were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10(6 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3 that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses.The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.

Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient

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Hu, Weibin [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Chen, Aizhong [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Miao, Yi [Shanghai Xuhui Central Hospital, Shanghai 200031 (China); Xia, Shengli [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Ling, Zhiyang; Xu, Ke; Wang, Tongyan [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Shu, Yuelong [Chinese Center for Disease Control and Prevention, Beijing 102206 (China); Ma, Xiaowei [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Xu, Bianli; Zhang, Jin [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Lin, Xiaojun, E-mail: linxiaojun@hualan.com [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Bian, Chao, E-mail: cbian@sibs.ac.cn [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Sun, Bing, E-mail: bsun@sibs.ac.cn [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

2013-01-20

Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarily targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.

Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient

International Nuclear Information System (INIS)

Hu, Weibin; Chen, Aizhong; Miao, Yi; Xia, Shengli; Ling, Zhiyang; Xu, Ke; Wang, Tongyan; Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling; Shu, Yuelong; Ma, Xiaowei; Xu, Bianli; Zhang, Jin; Lin, Xiaojun; Bian, Chao; Sun, Bing

2013-01-01

Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarily targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.

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...

CLINICAL STUDIES OF REACTOGENICITY, SAFETY AND IMMUNOGENICITY OF LIVE MONOVALENT INFLUENZA VACCINE (STRAIN А/17/CALIFORNIA/2009/38 — H1N1 IN CHILDREN

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D.S. Bushmenkov

2010-01-01

Full Text Available Results of performed pre-clinical and clinical studies with volunteers 18-60 years old allowed registration of vaccine «INFLUVIR» (live monovalent vaccine for the prophylaxis of influenza A/H1N1, strain A/17/California/2009/38 (H1N1, developed by NPO «Microgen» in Russian Federation so timely vaccination campaign was performed. As a result, the level of morbidity with influenza A/H1N1 in Russia was decreased, and development of complication was prevented. Clinical studies in different groups of children were performed for the purpose of widening indications for vaccine «INFLUVIR» administration. According to the results of studies vaccine «INFLUVIR» has good tolerability and safety, low reactogenicity, and significant immunogenicity. This fact will allow changing of present normative documentation and administration of «INFLUVIR» in children of different age for prophylaxis of influenza A/H1N1.Key words: children, influenza, virus A/H1N1, live influenza vaccine, tolerability, safety, immunogenicity.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:101-105

Knowledge, attitudes and anxiety towards influenza A/H1N1 vaccination of healthcare workers in Turkey

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Tanriverdi Derya

2010-09-01

Full Text Available Abstract Background This study aimed to analyze the factors associated with knowledge and attitudes about influenza A (H1N1 and vaccination, and possible relations of these factors with anxiety among healthcare workers (HCW. Methods The study used a cross-sectional descriptive design, and it was carried out between 23 November and 4 December 2009. A total of 300 HCW from two hospitals completed a questionnaire. Data collection tools comprised a questionnaire and the State-Trait Anxiety Inventory (STAI. Results Vaccination rate for 2009 pandemic influenza A(H1N1 among HCW was low (12.7%. Most of the respondents believed the vaccine was not safe and protective. Vaccination refusal was mostly related to the vaccine's side effects, disbelief to vaccine's protectiveness, negative news about the vaccine and the perceived negative attitude of the Prime Minister to the vaccine. State anxiety was found to be high in respondents who felt the vaccine was unsafe. Conclusions HCW considered the seriousness of the outbreak, their vaccination rate was low. In vaccination campaigns, governments have to aim at providing trust, and media campaigns should be used to reinforce this trust as well. Accurate reporting by the media of the safety and efficacy of influenza vaccines and the importance of vaccines for the public health would likely have a positive influence on vaccine uptake. Uncertain or negative reporting about the vaccine is detrimental to vaccination efforts.

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

Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine.

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Nuriban Valero-Pacheco

Full Text Available The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs, have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.

Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (δ-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus.

Science.gov (United States)

Gauger, Phillip C; Vincent, Amy L; Loving, Crystal L; Lager, Kelly M; Janke, Bruce H; Kehrli, Marcus E; Roth, James A

2011-03-24

Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (δ-cluster) H1 six and three weeks before challenge with H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies. Published by Elsevier Ltd.

Monitoring adverse events of the vaccination campaign against influenza A (H1N1) in the Netherlands

NARCIS (Netherlands)

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

2010-01-01

BACKGROUND: In November 2009, a vaccination campaign against Influenza A (H1N1) was started in the Netherlands. The accelerated registration procedure of the vaccines used in this campaign and the use of these vaccines on a large scale indicated a need for real-time safety monitoring. OBJECTIVE: To

Effectiveness of a MF-59™-adjuvanted pandemic influenza vaccine to prevent 2009 A/H1N1 influenza-related hospitalisation; a matched case-control study

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van der Sande Marianne AB

2011-07-01

Full Text Available Abstract Background During the 2009 influenza A/H1N1 pandemic, adjuvanted influenza vaccines were used for the first time on a large scale. Results on the effectiveness of the vaccines in preventing 2009 influenza A/H1N1-related hospitalisation are scanty and varying. Methods We conducted a matched case-control study in individuals with an indication for vaccination due to underlying medical conditions and/or age ≥ 60 years in the Netherlands. Cases were patients hospitalised with laboratory-confirmed 2009 A/H1N1 influenza infection between November 16, 2009 and January 15, 2010. Controls were matched to cases on age, sex and type of underlying medical condition(s and drawn from an extensive general practitioner network. Conditional logistic regression was used to estimate the vaccine effectiveness (VE = 1 - OR. Different sensitivity analyses were used to assess confounding by severity of underlying medical condition(s and the effect of different assumptions for missing dates of vaccination. Results 149 cases and 28,238 matched controls were included. It was estimated that 22% of the cases and 28% of the controls received vaccination more than 7 days before the date of onset of symptoms in cases. A significant number of breakthrough infections were observed. The VE was estimated at 19% (95%CI -28-49. After restricting the analysis to cases with controls suffering from severe underlying medical conditions, the VE was 49% (95%CI 16-69. Conclusions The number of breakthrough infections, resulting in modest VE estimates, suggests that the MF-59™ adjuvanted vaccine may have had only a limited impact on preventing 2009 influenza A/H1N1-related hospitalisation in this setting. As the main aim of influenza vaccination programmes is to reduce severe influenza-related morbidity and mortality from influenza in persons at high risk of complications, a more effective vaccine, or additional preventive measures, are needed.

International collaboration to assess the risk of Guillain Barré Syndrome following Influenza A (H1N1) 2009 monovalent vaccines

NARCIS (Netherlands)

C. Dodd (Caitlin); S.A. Romio (Silvana); S. Black (Steve); C. Vellozzi (Claudia); N.J. Andrews (Nick); M.C.J.M. Sturkenboom (Miriam); P. Zuber (Patrick); W. Hua (Wei); J. Bonhoeffer (Jan); J. Buttery (Jim); N. Crawford (Nigel); G. Deceuninck (Genevieve); C.S. de Vries (Corinne); P. de Wals (Philippe); D. Gimeno (David); H. Heijbel (Harald); H. Hughes (Hayley); K. Hur (Kwan); A. Hviid (Anders); J. Kelman (Jeffrey); T. Kilpi (Tehri); S.K. Chuang (S.); T. Macartney (Thomas); M. Rett (Melisa); V.R. Lopez-Callada (Vesta Richardson); D. Salmon (Daniel); F.G. Sanchez (Francisco Gimenez); N. Sanz (Nuria); B. Silverman (Bernard); J. Storsaeter (Jann); U. Thirugnanam (Umapathi); N.A.T. van der Maas (Nicoline); K. Yih (Katherine); T. Zhang (Teng Fei); H.S. Izurieta (Hector); B.J. Addis; A. Akhtar (Aysha); J. Cope (Judith); R.L. Davis (Robert); P. Gargiullo (Paul); X. Kurz (Xavier); B. Law (Barbara); I. Sahinovic (Isabelle); J. Tokars (Jerry); P. Serrano (Pedro); A. Cheng (Aixin); N.J. Andrews (Nick); P. Charles (Pat); H. Clothier (Hazel); B. Day (Bruce); T. Day (Timothy); P. Gates (Peter); R. MacDonnell (Richard); L. Roberts (Les); V. Rodriguez-Casero (Vic-toria); T. Wijeratne (Tissa); H.A.L. Kiers (Henk); C. Blyth (Christopher); R. Booy (Robert); E. Elliott (Elizabeth); M.R. Gold (Michael); H. Marshall; P. McIntyre (Peter); P. Richmond (Peter); J. Royle (Jenny); N.W. Wood (Nicholas); Y. Zurynski (Yvonne); G. Calvo (Gonzalo); M. Campins (Magda); N. Corominas (Nuria); F. Torres (Ferran); V. Valls; A. Vilella (Ángels); A. Dutra (Amalia); A. Eick-Cost (Angelia); H.M. Jackson (Henry); K. Garman (Katherine); Z. Hu (Zheng); J. Rigo; J. Badoo (Judith); D Cho (David); L.L. Polakowski (Laura); S.K. Sandhu (Sukhminder); G. Sun (Guoying); H.-S.S. Chan (Hoi-Shan Sophelia); K.-Y. Chan (Kwok-Yin); R. Cheung (Raymond); Y-F. Cheung (Yuk-Fai); S. Cherk (Sharon); S.K Chuang (S.); D. Fok (Dennis); B.-H. Fung (Bun-Hey); K.-F. Ko (Kwai-Fu); K.W. Lau (Ka Wing); K.-K. Lau (Kwok-Kwong); P. Li (Pulin); H.-T. Liu (Hui-Tung); S.-H. Liu (Shao-Haei); K. Mok (Kin); J. So (Joanna); W. Wong (Winnie); S.-P. Wu (Shun-Ping); V. Avagyan (Vardan); R. Ball (Robert); D. Burwen (Dale); R.L. Franks (Riley); J.M. Gibbs (Jonathan); R.E. Kliman (Rebecca); S. Kropp (Silke); T.E. MaCurdy (Thomas); D.B. Martin (David); S.-D.K. Sandhu (Sukhmin-Der); B.B. Worrall (Bradford B.); D.E.F. Fuentes (Dra. Elvira Fuentes); P.C.O. González (Paola Carolina Ojeda); V.F. Reyna (Valerie ); M. Kulldorff (Martin); G. Lee (Grace); T.A. Lieu (Tracy); S. Platt; G.D. Serres (Gaston De); K. Jabin (Kamilah); B.L.S. Soh (Bee Leng Sally); L. Arnheim-Dahlström (Lisen); A. Castot (Anne); H.E. de Melker (Hester); J.P. Dieleman (Jeanne); J. Hallgren (Jonal); B.C. Jacobs (Bart); K. Johansen (Kari); P Kramarz (Piotr); M. Lapeyre (Maryse); T. Leino (Tuija); D. Mølgaard-Nielsen (Ditte); M. Mosseveld (Mees); H.K. Olberg (Henning K); C.-M. Sammon (Cor-Mac); C. Saussier (Christel); M.J. Schuemie (Martijn); A. Sommet (Agnès); P. Sparen (Pär); H. Svanström (Henrik); A.M. Vanrolleghem (Ann M.); D.M. Weibel (Daniel); J.D. Domingo (Javier Diez); J.L. Esparza (José LuísMicó); R.M.O. Lucas (Rafael M. Ortí); J.B.M. Maseres (Juan B. Mollar); J.L.A. Sánchez (José Luís Alfonso); M.G. Sánchez (Mercedes Garcés); V.Z. Viguer (Vicente Zanón); F. Cunningham (Francesca); B. Thakkar (Bharat); R. Zhang (Rongping)

2013-01-01

textabstractBackground: The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barré syndrome (GBS), which

Clinical outcomes of seasonal influenza and pandemic influenza A (H1N1 in pediatric inpatients

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Budd Alicia

2010-10-01

Full Text Available Abstract Background In April 2009, a novel influenza A H1N1 (nH1N1 virus emerged and spread rapidly worldwide. News of the pandemic led to a heightened awareness of the consequences of influenza and generally resulted in enhanced infection control practices and strengthened vaccination efforts for both healthcare workers and the general population. Seasonal influenza (SI illness in the pediatric population has been previously shown to result in significant morbidity, mortality, and substantial hospital resource utilization. Although influenza pandemics have the possibility of resulting in considerable illness, we must not ignore the impact that we can experience annually with SI. Methods We compared the outcomes of pediatric patients ≤18 years of age at a large urban hospital with laboratory confirmed influenza and an influenza-like illness (ILI during the 2009 pandemic and two prior influenza seasons. The primary outcome measure was hospital length of stay (LOS. All variables potentially associated with LOS based on univariable analysis, previous studies, or hypothesized relationships were included in the regression models to ensure adjustment for their effects. Results There were 133 pediatric cases of nH1N1 admitted during 2009 and 133 cases of SI admitted during the prior 2 influenza seasons (2007-8 and 2008-9. Thirty-six percent of children with SI and 18% of children with nH1N1 had no preexisting medical conditions (p = 0.14. Children admitted with SI had 1.73 times longer adjusted LOS than children admitted for nH1N1 (95% CI 1.35 - 2.13. There was a trend towards more children with SI requiring mechanical ventilation compared with nH1N1 (16 vs.7, p = 0.08. Conclusions This study strengthens the growing body of evidence demonstrating that SI results in significant morbidity in the pediatric population. Pandemic H1N1 received considerable attention with strong media messages urging people to undergo vaccination and encouraging improved

Immunogenicity and safety of cell-derived MF59®-adjuvanted A/H1N1 influenza vaccine for children

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Knuf, Markus; Leroux-Roels, Geert; Rümke, Hans; Rivera, Luis; Pedotti, Paola; Arora, Ashwani Kumar; Lattanzi, Maria; Kieninger, Dorothee; Cioppa, Giovanni Della

2015-01-01

Mass immunization of children has the potential to decrease infection rates and prevent the transmission of influenza. We evaluated the immunogenicity, safety, and tolerability of different formulations of cell-derived MF59-adjuvanted and nonadjuvanted A/H1N1 influenza vaccine in children and adolescents. This was a randomized, single-blind, multicenter study with a total of 666 healthy subjects aged 6 months–17 y in one of 3 vaccination groups, each receiving formulations containing different amounts of influenza A/H1N1 antigen with or without MF59. A booster trivalent seasonal MF59 vaccine was administered one year after primary vaccinations. Antibody titers were assessed by hemagglutination inhibition (HI) and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks post booster). Safety was monitored throughout the study. One vaccination with 3.75 μg of A/H1N1 antigen formulated with 50% MF59 (3.75_halfMF59) or 7.5 μg of A/H1N1 antigen formulated with 100% MF59 (7.5_fullMF59) induced an HI titer ≥1:40 in >70% of children in the 1–vaccinations with nonadjuvanted 15 μg A/H1N1 antigen were needed to achieve this response in the 1–children aged 6–11 months, 1 dose of 7.5_fullMF59 resulted in an HI titer ≥1:40 in >70% while 2 doses of 3.75_halfMF59 were required to achieve this result. All vaccines were well tolerated. Our findings support the immunogenicity and safety of the 3.75_halfMF59 (2 doses for children vaccine formulations for use in children and adolescents aged 6 months to 17 y The use of the 3.75_halfMF59 could have the benefit of antigen and adjuvant sparing, increasing the available vaccine doses allowing vaccination of more people. PMID:25621884

A polyvalent influenza A DNA vaccine induces heterologous immunity and protects pigs against pandemic A(H1N1)pdm09 virus infection

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Bragstad, Karoline; Vinner, Lasse; Hansen, Mette Sif

2013-01-01

seasonal and emerging influenza viruses. We have developed an alternative influenza vaccine based on DNA expressing selected influenza proteins of pandemic and seasonal origin. In the current study, we investigated the protection of a polyvalent influenza DNA vaccine approach in pigs. We immunised pigs...... intradermally with a combination of influenza DNA vaccine components based on the pandemic 1918 H1N1 (M and NP genes), pandemic 2009 H1N1pdm09 (HA and NA genes) and seasonal 2005 H3N2 genes (HA and NA genes) and investigated the protection against infection with virus both homologous and heterologous to the DNA...... of this DNA vaccine to limit virus shedding may have an impact on virus spread among pigs which could possibly extend to humans as well, thereby diminishing the risk for epidemics and pandemics to evolve....

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

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

Cost-effectiveness of 2009 pandemic influenza A(H1N1 vaccination in the United States.

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Lisa A Prosser

Full Text Available Pandemic influenza A(H1N1 (pH1N1 was first identified in North America in April 2009. Vaccination against pH1N1 commenced in the U.S. in October 2009 and continued through January 2010. The objective of this study was to evaluate the cost-effectiveness of pH1N1 vaccination.A computer simulation model was developed to predict costs and health outcomes for a pH1N1 vaccination program using inactivated vaccine compared to no vaccination. Probabilities, costs and quality-of-life weights were derived from emerging primary data on pH1N1 infections in the US, published and unpublished data for seasonal and pH1N1 illnesses, supplemented by expert opinion. The modeled target population included hypothetical cohorts of persons aged 6 months and older stratified by age and risk. The analysis used a one-year time horizon for most endpoints but also includes longer-term costs and consequences of long-term sequelae deaths. A societal perspective was used. Indirect effects (i.e., herd effects were not included in the primary analysis. The main endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted life year (QALY gained. Sensitivity analyses were conducted.For vaccination initiated prior to the outbreak, pH1N1 vaccination was cost-saving for persons 6 months to 64 years under many assumptions. For those without high risk conditions, incremental cost-effectiveness ratios ranged from $8,000-$52,000/QALY depending on age and risk status. Results were sensitive to the number of vaccine doses needed, costs of vaccination, illness rates, and timing of vaccine delivery.Vaccination for pH1N1 for children and working-age adults is cost-effective compared to other preventive health interventions under a wide range of scenarios. The economic evidence was consistent with target recommendations that were in place for pH1N1 vaccination. We also found that the delays in vaccine availability had a substantial impact on the cost-effectiveness of

Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy

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Renata Miossi

2013-01-01

Full Text Available OBJECTIVE: To assess the potential acute effects regarding the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with mixed connective tissue disease and healthy controls. METHODS: Sixty-nine mixed connective tissue disease patients that were confirmed by Kasukawa's classification criteria and 69 age- and gender-matched controls participated in the study; the participants were vaccinated with the non-adjuvanted influenza A/California/7/2009 (H1N1 virus-like strain. The percentages of seroprotec-tion, seroconversion, geometric mean titer and factor increase in the geometric mean titer were calculated. The patients were clinically evaluated, and blood samples were collected pre- and 21 days post-vaccination to evaluate C-reactive protein, muscle enzymes and autoantibodies. Anti-H1N1 titers were determined using an influenza hemagglutination inhibition assay. ClinicalTrials.gov: NCT01151644. RESULTS: Before vaccination, no difference was observed regarding the seroprotection rates (p = 1.0 and geometric mean titer (p = 0.83 between the patients and controls. After vaccination, seroprotection (75.4% vs. 71%, (p = 0.7, seroconversion (68.1% vs. 65.2%, (p = 1.00 and factor increase in the geometric mean titer (10.0 vs. 8.0, p = 0.40 were similar in the two groups. Further evaluation of seroconversion in patients with and without current or previous history of muscle disease (p = 0.20, skin ulcers (p = 0.48, lupus-like cutaneous disease (p = 0.74, secondary Sjogren syndrome (p = 0.78, scleroderma-pattern in the nailfold capillaroscopy (p = 1.0, lymphopenia #1000/mm³ on two or more occasions (p = 1.0, hypergammaglobulinemia $1.6 g/d (p = 0.60, pulmonary hypertension (p = 1.0 and pulmonary fibrosis (p = 0.80 revealed comparable rates. Seroconversion rates were also similar in patients with and without immunosuppressants. Disease parameters, such as C-reactive protein (p = 0.94, aldolase (p = 0.73, creatine

[Assessment of the MF59-adjuvanted pandemic influenza A/H1N1 vaccine. Systematic review of literature].

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Ruiz-Aragón, J; Grande Tejada, A M; Márquez-Peláez, S; Molina Linde, J M; Yang, R

2013-10-01

To assess the efficacy and safety of MF59-adjuvanted pandemic influenza A/H1N1 vaccine in children. A systematic review of the literature was performed after searching the MedLine and Embase electronic databases, and manual search in specialties journals, with MeSH terms and and free terms. Inclusion criteria were clinical trials with children vaccinated with MF59-adjuvanted influenza A/H1N1 vaccine, compared with other vaccines doses with/without MF59-adjuvanted. The immunogenicity and safety of the vaccine was recorded. The quality of the studies included was assessed by CASPe checklist. Four clinical trials with moderate quality were selected. The local and systemic adverse effects were rare and mild, with no differences between groups. Seroconversion and seroprotection levels were higher with MF59-adjuvanted vaccines. Antibody titres were also higher with the adjuvant vaccines. The adjuvant vaccine has a good efficacy and safety profile. The adverse effects that may occur are common and appear similarly in both vaccination groups. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

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.

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

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.

The 2009 A (H1N1) influenza virus pandemic: A review.

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Girard, Marc P; Tam, John S; Assossou, Olga M; Kieny, Marie Paule

2010-07-12

In March and early April 2009 a new swine-origin influenza virus (S-OIV), A (H1N1), emerged in Mexico and the USA. The virus quickly spread worldwide through human-to-human transmission. In view of the number of countries and communities which were reporting human cases, the World Health Organization raised the influenza pandemic alert to the highest level (level 6) on June 11, 2009. The propensity of the virus to primarily affect children, young adults and pregnant women, especially those with an underlying lung or cardiac disease condition, and the substantial increase in rate of hospitalizations, prompted the efforts of the pharmaceutical industry, including new manufacturers from China, Thailand, India and South America, to develop pandemic H1N1 influenza vaccines. All currently registered vaccines were tested for safety and immunogenicity in clinical trials on human volunteers. All were found to be safe and to elicit potentially protective antibody responses after the administration of a single dose of vaccine, including split inactivated vaccines with or without adjuvant, whole-virion vaccines and live-attenuated vaccines. The need for an increased surveillance of influenza virus circulation in swine is outlined. Copyright 2010. Published by Elsevier Ltd.

Multivalent HA DNA vaccination protects against highly pathogenic H5N1 avian influenza infection in chickens and mice.

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Srinivas Rao

Full Text Available Sustained outbreaks of highly pathogenic avian influenza (HPAI H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses.The ability of DNA vaccines encoding hemagglutinin (HA proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs. The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination. In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 microg DNA given twice either by intramuscular needle injection or with a needle-free device.DNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species. In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates.

Prophylactic and therapeutic efficacy of avian antibodies against influenza virus H5N1 and H1N1 in mice.

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Huan H Nguyen

Full Text Available BACKGROUND: Pandemic influenza poses a serious threat to global health and the world economy. While vaccines are currently under development, passive immunization could offer an alternative strategy to prevent and treat influenza virus infection. Attempts to develop monoclonal antibodies (mAbs have been made. However, passive immunization based on mAbs may require a cocktail of mAbs with broader specificity in order to provide full protection since mAbs are generally specific for single epitopes. Chicken immunoglobulins (IgY found in egg yolk have been used mainly for treatment of infectious diseases of the gastrointestinal tract. Because the recent epidemic of highly pathogenic avian influenza virus (HPAIV strain H5N1 has resulted in serious economic losses to the poultry industry, many countries including Vietnam have introduced mass vaccination of poultry with H5N1 virus vaccines. We reasoned that IgY from consumable eggs available in supermarkets in Vietnam could provide protection against infections with HPAIV H5N1. METHODS AND FINDINGS: We found that H5N1-specific IgY that are prepared from eggs available in supermarkets in Vietnam by a rapid and simple water dilution method cross-protect against infections with HPAIV H5N1 and related H5N2 strains in mice. When administered intranasally before or after lethal infection, the IgY prevent the infection or significantly reduce viral replication resulting in complete recovery from the disease, respectively. We further generated H1N1 virus-specific IgY by immunization of hens with inactivated H1N1 A/PR/8/34 as a model virus for the current pandemic H1N1/09 and found that such H1N1-specific IgY protect mice from lethal influenza virus infection. CONCLUSIONS: The findings suggest that readily available H5N1-specific IgY offer an enormous source of valuable biological material to combat a potential H5N1 pandemic. In addition, our study provides a proof-of-concept for the approach using virus

Obstetricians and the 2009-2010 H1N1 vaccination effort: implications for future pandemics.

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Clark, Sarah J; Cowan, Anne E; Wortley, Pascale M

2013-09-01

Our objective was to describe the experiences of obstetricians during the 2009-2010 H1N1 vaccination campaign in order to identify possible improvements for future pandemic situations. We conducted a cross-sectional mail survey of a national random sample of 4,000 obstetricians, fielded in Summer 2010. Survey items included availability, recommendation, and patient acceptance of H1N1 vaccine; prioritization of H1N1 vaccine when supply was limited; problems with H1N1 vaccination; and likelihood of providing vaccine during a future influenza pandemic. Response rate was 66 %. Obstetricians strongly recommended H1N1 vaccine during the second (85 %) and third (86 %) trimesters, and less often during the first trimester (71 %) or the immediate postpartum period (76 %); patient preferences followed a similar pattern. H1N1 vaccine was typically available in outpatient obstetrics clinics (80 %). Overall vaccine supply was a major problem for 30 % of obstetricians, but few rated lack of thimerosal-free vaccine as a major problem (12 %). Over half of obstetricians had no major problems with the H1N1 vaccine campaign. Based on this experience, 74 % would be "very likely" and 12 % "likely" to provide vaccine in the event of a future influenza pandemic. Most obstetricians strongly recommended H1N1 vaccine, had few logistical problems beyond limited vaccine supply, and are willing to vaccinate in a future pandemic. Addressing concerns about first-trimester vaccination, developing guidance for prioritization of vaccine in the event of severe supply constraints, and continued facilitation of the logistical aspects of vaccination should be emphasized in future influenza pandemics.

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.

Influenza A(H1N1)pdm09 vaccination policies and coverage in Europe.

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Mereckiene, J; Cotter, S; Weber, J T; Nicoll, A; D'Ancona, F; Lopalco, P L; Johansen, K; Wasley, A M; Jorgensen, P; Lévy-Bruhl, D; Giambi, C; Stefanoff, P; Dematte, L; O'Flanagan, D

2012-01-26

In August 2010 the Vaccine European New Integrated Collaboration Effort (VENICE) project conducted a survey to collect information on influenza A(H1N1)pdm09 vaccination policies and vaccination coverage in the European Union (EU), Norway and Iceland. Of 29 responding countries, 26 organised national pandemic influenza vaccination and one country had recommendations for vaccination but did not have a specific programme. Of the 27 countries with vaccine recommendations, all recommended it for healthcare workers and pregnant women. Twelve countries recommended vaccine for all ages. Six and three countries had recommendations for specific age groups in children and in adults, countries for specific adult age groups. Most countries recommended vaccine for those in new risk groups identified early in the pandemic such as morbid obese and people with neurologic diseases. Two thirds of countries started their vaccination campaigns within a four week period after week 40/2009. The reported vaccination coverage varied between countries from 0.4% to 59% for the entire population (22 countries); 3% to 68% for healthcare workers (13 countries); 0% to 58% for pregnant women (12 countries); 0.2% to 74% for children (12 countries). Most countries identified similar target groups for pandemic vaccine, but substantial variability in vaccination coverage was seen. The recommendations were in accordance with policy advice from the EU Health Security Committee and the World Health Organization.

Influenza A(H1N1)pdm09 vaccination policies and coverage in Europe.

LENUS (Irish Health Repository)

Mereckiene, J

2012-06-01

In August 2010 the Vaccine European New Integrated Collaboration Effort (VENICE) project conducted a survey to collect information on influenza A(H1N1)pdm09 vaccination policies and vaccination coverage in the European Union (EU), Norway and Iceland. Of 29 responding countries, 26 organised national pandemic influenza vaccination and one country had recommendations for vaccination but did not have a specific programme. Of the 27 countries with vaccine recommendations, all recommended it for healthcare workers and pregnant women. Twelve countries recommended vaccine for all ages. Six and three countries had recommendations for specific age groups in children and in adults, countries for specific adult age groups. Most countries recommended vaccine for those in new risk groups identified early in the pandemic such as morbid obese and people with neurologic diseases. Two thirds of countries started their vaccination campaigns within a four week period after week 40\\/2009. The reported vaccination coverage varied between countries from 0.4% to 59% for the entire population (22 countries); 3% to 68% for healthcare workers (13 countries); 0% to 58% for pregnant women (12 countries); 0.2% to 74% for children (12 countries). Most countries identified similar target groups for pandemic vaccine, but substantial variability in vaccination coverage was seen. The recommendations were in accordance with policy advice from the EU Health Security Committee and the World Health Organization.

Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1 2009 vaccines: a multinational self-controlled case series in Europe.

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Silvana Romio

Full Text Available BACKGROUND: The risk of Guillain-Barré syndrome (GBS following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1pdm09 immunization campaign. This study aimed to estimate the risk of GBS following influenza A(H1N1pdm09 vaccination. METHODS: A self-controlled case series (SCCS analysis was performed in Denmark, Finland, France, Netherlands, Norway, Sweden, and the United Kingdom. Information was collected according to a common protocol and standardised procedures. Cases classified at levels 1-4a of the Brighton Collaboration case definition were included. The risk window was 42 days starting the day after vaccination. Conditional Poisson regression and pooled random effects models estimated adjusted relative incidences (RI. Pseudo likelihood and vaccinated-only methods addressed the potential contraindication for vaccination following GBS. RESULTS: Three hundred and three (303 GBS and Miller Fisher syndrome cases were included. Ninety-nine (99 were exposed to A(H1N1pdm09 vaccination, which was most frequently adjuvanted (Pandemrix and Focetria. The unadjusted pooled RI for A(H1N1pdm09 vaccination and GBS was 3.5 (95% Confidence Interval (CI: 2.2-5.5, based on all countries. This lowered to 2.0 (95% CI: 1.2-3.1 after adjustment for calendartime and to 1.9 (95% CI: 1.1-3.2 when we accounted for contra-indications. In a subset (Netherlands, Norway, and United Kingdom we further adjusted for other confounders and there the RI decreased from 1.7 (adjusted for calendar month to 1.4 (95% CI: 0.7-2.8, which is the main finding. CONCLUSION: This study illustrates the potential of conducting European collaborative vaccine safety studies. The main, fully adjusted analysis, showed that the RI of GBS was not significantly elevated after influenza A(H1N1pdm09 vaccination (RI = 1.4 (95% CI: 0.7-2.8. Based on the upper limits of the pooled estimate we can rule out with

Risk for Congenital Malformation With H1N1 Influenza Vaccine: A Cohort Study With Sibling Analysis.

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Ludvigsson, Jonas F; Ström, Peter; Lundholm, Cecilia; Cnattingius, Sven; Ekbom, Anders; Örtqvist, Åke; Feltelius, Nils; Granath, Fredrik; Stephansson, Olof

2016-12-20

Earlier studies reporting varying risk estimates for congenital malformation in offspring of mothers undergoing vaccination against H1N1 influenza during pregnancy did not consider the potential role of confounding by familial (genetic and shared environmental) factors. To evaluate an association between maternal H1N1 vaccination during pregnancy and offspring malformation, with familial factors taken into account. Population-based prospective study. Sweden. Liveborn offspring born between 1 October 2009 and 1 October 2011 to mothers receiving monovalent AS03-adjuvanted H1N1 influenza vaccine (Pandemrix [GlaxoSmithKline]) during pregnancy. A total of 40 983 offspring were prenatally exposed to the vaccine, 14 385 were exposed within the first trimester (14 weeks), and 7502 were exposed during the first 8 weeks of pregnancy. Exposed offspring were compared with 197 588 unexposed offspring. Corresponding risks in exposed versus unexposed siblings were also estimated. Congenital malformation, with subanalyses for congenital heart disease, oral cleft, and limb deficiency. Congenital malformation was observed in 2037 (4.97%) exposed offspring and 9443 (4.78%) unexposed offspring. Adjusted risk for congenital malformation was 4.98% in exposed offspring versus 4.96% in unexposed offspring (risk difference, 0.02% [95% CI, -0.26% to 0.30%]). The corresponding risk differences were 0.16% (CI, -0.23% to 0.56%) for vaccination during the first trimester and 0.10% (CI, -0.41% to 0.62%) for vaccination in the first 8 weeks. Using siblings as comparators yielded no statistically significant risk differences. The study was based on live births, and the possibility that data on miscarriage or induced abortion could have influenced the findings cannot be ruled out. Study power was limited in analyses of specific malformations. When intrafamilial factors were taken into consideration, H1N1 vaccination during pregnancy did not seem to be linked to overall congenital malformation in

Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.

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Nfon, Charles; Berhane, Yohannes; Pasick, John; Embury-Hyatt, Carissa; Kobinger, Gary; Kobasa, Darwyn; Babiuk, Shawn

2012-01-01

There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI). In addition, heterologous cell mediated immunity (CMI) was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.

Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.

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Charles Nfon

Full Text Available There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI. In addition, heterologous cell mediated immunity (CMI was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.

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.

Duration of 18F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination

International Nuclear Information System (INIS)

Thomassen, Anders; Lerberg Nielsen, Anne; Gerke, Oke; Johansen, Allan; Petersen, Henrik

2011-01-01

The aim of our study was to investigate the occurrence of fluorodeoxyglucose (FDG) avidity in draining axillary lymph nodes after vaccination against influenza (H1N1v pandemic and seasonal) and to determine the period of increased FDG uptake. During December 2009, patients referred for 18 F-FDG positron emission tomography (PET)/CT scans (n = 293) filled in a questionnaire concerning vaccination type (seasonal and/or H1N1v), time and anatomical localization of vaccination. Only injections in deltoid regions were evaluated, thus ensuring that draining lymph nodes were axillary. If more vaccinations had been given, only the latest vaccination was evaluated in each deltoid region. Of all patients who underwent PET/CT scans during December 2009, 26% had been vaccinated with at least one influenza vaccination in the deltoid region. A total of 92 'draining' and 60 'reference' (i.e. contralateral, non-vaccinated) axillary lymph nodes were evaluated in 61 patients (19 of 61 patients were scanned twice). The maximal intensity in FDG uptake (SUV max ) in draining lymph nodes was 5 g/ml body weight (BW), whereas the maximal intensity in reference lymph nodes was 1.9 g/ml BW. The SUV max was normalized approximately 40 days after vaccination. No significant enlargement of metabolically active draining lymph nodes could be demonstrated on CT scan. Chemotherapy or immunosuppressive drugs given within 2 weeks from vaccination did not affect SUV max in the axillary lymph nodes. Influenza vaccination may lead to FDG-avid draining lymph nodes beyond 1 month. (orig.)

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.

Development of a dual-protective live attenuated vaccine against H5N1 and H9N2 avian influenza viruses by modifying the NS1 gene.

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Choi, Eun-hye; Song, Min-Suk; Park, Su-Jin; Pascua, Philippe Noriel Q; Baek, Yun Hee; Kwon, Hyeok-il; Kim, Eun-Ha; Kim, Semi; Jang, Hyung-Kwan; Poo, Haryoung; Kim, Chul-Joong; Choi, Young Ki

2015-07-01

An increasing number of outbreaks of avian influenza H5N1 and H9N2 viruses in poultry have caused serious economic losses and raised concerns for human health due to the risk of zoonotic transmission. However, licensed H5N1 and H9N2 vaccines for animals and humans have not been developed. Thus, to develop a dual H5N1 and H9N2 live-attenuated influenza vaccine (LAIV), the HA and NA genes from a virulent mouse-adapted avian H5N2 (A/WB/Korea/ma81/06) virus and a recently isolated chicken H9N2 (A/CK/Korea/116/06) virus, respectively, were introduced into the A/Puerto Rico/8/34 backbone expressing truncated NS1 proteins (NS1-73, NS1-86, NS1-101, NS1-122) but still possessing a full-length NS gene. Two H5N2/NS1-LAIV viruses (H5N2/NS1-86 and H5N2/NS1-101) were highly attenuated compared with the full-length and remaining H5N2/NS-LAIV viruses in a mouse model. Furthermore, viruses containing NS1 modifications were found to induce more IFN-β activation than viruses with full-length NS1 proteins and were correspondingly attenuated in mice. Intranasal vaccination with a single dose (10(4.0) PFU/ml) of these viruses completely protected mice from a lethal challenge with the homologous A/WB/Korea/ma81/06 (H5N2), heterologous highly pathogenic A/EM/Korea/W149/06 (H5N1), and heterosubtypic highly virulent mouse-adapted H9N2 viruses. This study clearly demonstrates that the modified H5N2/NS1-LAIV viruses attenuated through the introduction of mutations in the NS1 coding region display characteristics that are desirable for live attenuated vaccines and hold potential as vaccine candidates for mammalian hosts.

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

A/H1N1 pandemic influenza vaccination: A retrospective evaluation of adverse maternal, fetal and neonatal outcomes in a cohort of pregnant women in Italy.

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Fabiani, Massimo; Bella, Antonino; Rota, Maria C; Clagnan, Elena; Gallo, Tolinda; D'Amato, Maurizio; Pezzotti, Patrizio; Ferrara, Lorenza; Demicheli, Vittorio; Martinelli, Domenico; Prato, Rosa; Rizzo, Caterina

2015-05-05

Although concerns about safety of influenza vaccination during pregnancy have been raised in the past, vaccination of pregnant women was recommended in many countries during the 2009 A/H1N1 pandemic influenza. A retrospective cohort study was conducted to evaluate the risk of adverse maternal, fetal and neonatal outcomes among pregnant women vaccinated with a MF59-adjuvanted A/H1N1 pandemic influenza vaccine. The study was carried out in four Italian regions (Piemonte, Friuli-Venezia-Giulia, Lazio, and Puglia) among 102,077 pregnant women potentially exposed during the second or third trimester of gestation to the vaccination campaign implemented in 2009/2010. Based on data retrieved from the regional administrative databases, the statistical analysis was performed using the Cox proportional-hazards model, adjusting for the propensity score to account for the potential confounding effect due to the socio-demographic characteristics and the clinical and reproductive history of women. A total of 100,332 pregnant women were eligible for the analysis. Of these, 2003 (2.0%) received the A/H1N1 pandemic influenza vaccination during the second or third trimester of gestation. We did not observe any statistically significant association between the A/H1N1 pandemic influenza vaccination and different maternal outcomes (hospital admissions for influenza, pneumonia, hypertension, eclampsia, diabetes, thyroid disease, and anaemia), fetal outcomes (fetal death after the 22nd gestational week) and neonatal outcomes (pre-term birth, low birth weight, low 5-min Apgar score, and congenital malformations). Pre-existing health-risk conditions (hospital admissions and drug prescriptions for specific diseases before the onset of pregnancy) were observed more frequently among vaccinated women, thus suggesting that concomitant chronic conditions increased vaccination uptake. The results of this study add some evidence on the safety of A/H1N1 pandemic influenza vaccination during

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.

Profiles of influenza A/H1N1 vaccine response using hemagglutination-inhibition titers.

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Jacobson, Robert M; Grill, Diane E; Oberg, Ann L; Tosh, Pritish K; Ovsyannikova, Inna G; Poland, Gregory A

2015-01-01

To identify distinct antibody profiles among adults 50-to-74 years old using influenza A/H1N1 HI titers up to 75 days after vaccination. Healthy subjects 50 to 74 years old received the 2010-2011 trivalent inactivated influenza vaccine. We measured venous samples from Days 0, 28, and 75 for HI and VNA and B-cell ELISPOTs. Of 106 subjects, HI titers demonstrated a ceiling effect for 11 or 10% for those with a pre-vaccination HI titer of 1:640 where no subject post-vaccination had an increase in titer. Of the remaining 95 subjects, only 37 or 35% overall had at least a 4-fold increase by Day 28. Of these 37, 3 waned at least 4-fold, and 13 others 2-fold. Thus 15% of the subjects showed waning antibody titers by Day 75. More than half failed to respond at all. The profiles populated by these subjects as defined by HI did not vary with age or gender. The VNA results mimicked the HI profiles, but the profiles for B-cell ELISPOT did not. HI titers at Days 0, 28, and 75 populate 4 biologically plausible profiles. Limitations include lack of consensus for operationally defining waning as well as for the apparent ceiling. Furthermore, though well accepted as a marker for vaccine response, assigning thresholds with HI has limitations. However, VNA closely matches HI in populating these profiles. Thus, we hold that these profiles, having face- and content-validity, may provide a basis for understanding variation in genomic and transcriptomic response to influenza vaccination in this age group.

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

DEFF Research Database (Denmark)

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...

Oligomeric recombinant H5 HA1 vaccine produced in bacteria protects ferrets from homologous and heterologous wild-type H5N1 influenza challenge and controls viral loads better than subunit H5N1 vaccine by eliciting high-affinity antibodies.

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Verma, Swati; Dimitrova, Milena; Munjal, Ashok; Fontana, Juan; Crevar, Corey J; Carter, Donald M; Ross, Ted M; Khurana, Surender; Golding, Hana

2012-11-01

Recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. In this study, we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric HA1 proteins from H5N1 (A/Vietnam/1203/04) with those of the egg-based licensed subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated twice with the oligomeric or monomeric rHA1 or with SU-H5N1 (Sanofi Pasteur) emulsified with Titermax adjuvant and were challenged with wild-type homologous (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005; clade 2.2) virus. Only the oligomeric rHA1 (not the monomeric rHA1) immunogen and the SU-H5N1 vaccine provided protection against the lethality and morbidity of homologous and heterologous highly pathogenic H5N1. Oligomeric rHA1 generated more cross-neutralizing antibodies and higher levels of serum antibody binding to HA1, with stronger avidity and a better IgG/IgM ratio, than monomeric HA1 and SU-H5N1 vaccines, as determined by surface plasmon resonance (SPR). Importantly, viral loads after heterologous H5N1 challenge were more efficiently controlled in ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1-vaccinated ferrets. The reduction of viral loads in the nasal washes correlated strongly with higher-avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and clade 2.2 viruses, as measured by SPR. This is the first study to show the role of antibody avidity for the HA1 globular head domain in reduction of viral loads in the upper respiratory tract, which could significantly reduce viral transmission.

MVA-based H5N1 vaccine affords cross-clade protection in mice against influenza A/H5N1 viruses at low doses and after single immunization.

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Joost H C M Kreijtz

Full Text Available Human infections with highly pathogenic avian influenza viruses of the H5N1 subtype, frequently reported since 2003, result in high morbidity and mortality. It is feared that these viruses become pandemic, therefore the development of safe and effective vaccines is desirable. MVA-based H5N1 vaccines already proved to be effective when two immunizations with high doses were used. Dose-sparing strategies would increase the number of people that can be vaccinated when the amount of vaccine preparations that can be produced is limited. Furthermore, protective immunity is induced ideally after a single immunization. Therefore the minimal requirements for induction of protective immunity with a MVA-based H5N1 vaccine were assessed in mice. To this end, mice were vaccinated once or twice with descending doses of a recombinant MVA expressing the HA gene of influenza virus A/Vietnam/1194/04. The protective efficacy was determined after challenge infection with the homologous clade 1 virus and a heterologous virus derived from clade 2.1, A/Indonesia/5/05 by assessing weight loss, virus replication and histopathological changes. It was concluded that MVA-based vaccines allowed significant dose-sparing and afford cross-clade protection, also after a single immunization, which are favorable properties for an H5N1 vaccine candidate.

Assessment of epicutaneous testing of a monovalent Influenza A (H1N1 2009 vaccine in egg allergic patients

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Pitt Tracy

2011-02-01

Full Text Available Abstract Background H1N1 is responsible for the first influenza pandemic in 41 years. In the fall of 2009, an H1N1 vaccine became available in Canada with the hopes of reducing the overall effect of the pandemic. The purpose of this study was to assess the safety of administering 2 different doses of a monovalent split virus 2009 H1N1 vaccine in egg allergic patients. Methods Patients were skin tested to the H1N1 vaccine in the outpatient paediatric and adult allergy and immunology clinics of the Health Sciences Centre and Children's Hospital of Winnipeg, Manitoba Canada. Individuals Results A total of 61 patients with egg allergy (history of an allergic reaction to egg with either positive skin test &/or specific IgE to egg >0.35 Ku/L were referred to our allergy clinics for skin testing to the H1N1 vaccine. 2 patients were excluded, one did not have a skin prick test to the H1N1 vaccine (only vaccine administration and the other passed an egg challenge during the study period. Ages ranged from 1 to 27 years (mean 5.6 years. There were 41(69.5% males and 18(30.5% females. All but one patient with a history of egg allergy, positive skin test to egg and/or elevated specific IgE level to egg had negative skin tests to the H1N1 vaccine. The 58 patients with negative skin testing to the H1N1 vaccine were administered the vaccine and observed for 30 minutes post vaccination with no adverse results. The patient with the positive skin test to the H1N1 vaccine was also administered the vaccine intramuscularly with no adverse results. Conclusions Despite concern regarding possible anaphylaxis to the H1N1 vaccine in egg allergic patients, in our case series 1/59(1.7% patients with sensitization to egg were also sensitized to the H1N1 vaccine. Administration of the H1N1 vaccine in egg allergic patients with negative H1N1 skin tests and observation is safe. Administering the vaccine in a 1 or 2 dose protocol without skin testing is a reasonable alternative

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.

Duration of {sup 18}F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination

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Thomassen, Anders; Lerberg Nielsen, Anne; Gerke, Oke; Johansen, Allan; Petersen, Henrik [OUH, Odense University Hospital, Department of Nuclear Medicine, Odense C (Denmark)

2011-05-15

The aim of our study was to investigate the occurrence of fluorodeoxyglucose (FDG) avidity in draining axillary lymph nodes after vaccination against influenza (H1N1v pandemic and seasonal) and to determine the period of increased FDG uptake. During December 2009, patients referred for {sup 18}F-FDG positron emission tomography (PET)/CT scans (n = 293) filled in a questionnaire concerning vaccination type (seasonal and/or H1N1v), time and anatomical localization of vaccination. Only injections in deltoid regions were evaluated, thus ensuring that draining lymph nodes were axillary. If more vaccinations had been given, only the latest vaccination was evaluated in each deltoid region. Of all patients who underwent PET/CT scans during December 2009, 26% had been vaccinated with at least one influenza vaccination in the deltoid region. A total of 92 'draining' and 60 'reference' (i.e. contralateral, non-vaccinated) axillary lymph nodes were evaluated in 61 patients (19 of 61 patients were scanned twice). The maximal intensity in FDG uptake (SUV{sub max}) in draining lymph nodes was 5 g/ml body weight (BW), whereas the maximal intensity in reference lymph nodes was 1.9 g/ml BW. The SUV{sub max} was normalized approximately 40 days after vaccination. No significant enlargement of metabolically active draining lymph nodes could be demonstrated on CT scan. Chemotherapy or immunosuppressive drugs given within 2 weeks from vaccination did not affect SUV{sub max} in the axillary lymph nodes. Influenza vaccination may lead to FDG-avid draining lymph nodes beyond 1 month. (orig.)

The European I-MOVE Multicentre 2013-2014 Case-Control Study. Homogeneous moderate influenza vaccine effectiveness against A(H1N1)pdm09 and heterogenous results by country against A(H3N2).

LENUS (Irish Health Repository)

Valenciano, Marta

2015-06-04

In the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013-2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013-2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season.

Adjuvanted A/H1N1 influenza vaccination during pregnancy : Description of a prospective cohort and spontaneously reported pregnancy-related adverse reactions in the Netherlands

NARCIS (Netherlands)

de Vries, Loes; van Hunsel, Florence; Cuppers-Maarschalkerweerd, Benedikte; van Puijenbroek, Eugène; van Grootheest, Kees

2014-01-01

BACKGROUND: During influenza pandemics, pregnant women have an increased risk of severe complications. Vaccination can diminish these complications. In the Netherlands, the adjuvanted vaccines Focetria® and Pandemrix® were used during the A/H1N1 (2009) influenza pandemic. The national vaccination

Kompliceret influenza A (H1N1) hos gravid i andet trimester

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Ersboell, Anne Schjoedt; Hesselvig, Anne Brun; Hedegaard, Morten

2012-01-01

A 27-year-old woman at 25 weeks of gestation was admitted to hospital due to bilateral pneumonia with increasing hypoxia. She was tested positive for influenza A (H1N1) and successfully treated with oral oseltamivir. Nine days after the admission pathological umbilical flows were recorded...... and an emergency caesarean was performed at 26 weeks + 2 days of gestation. The neonatal period was uncomplicated. Influenza A (H1N1) is especially dangerous in pregnant women and vaccination is important....

Continued dominance of pandemic A(H1N1 2009 influenza in Victoria, Australia in 2010

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James E. Fielding

2011-08-01

Full Text Available The 2010 Victorian influenza season was characterized by normal seasonal influenza activity and the dominance of the pandemic A(H1N1 2009 strain. General Practice Sentinel Surveillance rates peaked at 9.4 ILI cases per 1000 consultations in week 36 for metropolitan practices, and at 10.5 ILI cases per 1000 in the following week for rural practices. Of the 678 ILI cases, 23% were vaccinated, a significantly higher percentage than in previous years. A significantly higher percentage of ILI patients were swabbed in 2010 compared to 2003–2008, but similar to 2009, with a similar percentage being positive for influenza as in previous years. Vaccination rates increased with patient age. Melbourne Medical Deputising Service rates peaked in week 35 at 19.1 ILI cases per 1000 consultations. Of the 1914 cases of influenza notified to the Department of Health, Victoria, 1812 (95% were influenza A infections - 1001 (55% pandemic A(H1N1 2009, 4 (<1% A(H3N2 and 807 (45% not subtyped; 88 (5% were influenza B; and 14 (< 1% were influenza A and B co-infections. The World Health Organization Collaborating Centre for Reference and Research on Influenza tested 403 isolates of which 261 were positive for influenza, 250 of which were influenza A and 11 were influenza B. Ninety-two per cent of the influenza A viruses were pandemic A(H1N1 2009, and following antigenic analysis all of these were found to be similar to the current vaccine strain. Three viruses (0.9% were found to be oseltamivir resistant due to an H275Y mutation in the neuraminidase gene.

Vaccination with recombinant RNA replicon particles protects chickens from H5N1 highly pathogenic avian influenza virus.

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Stefan J Halbherr

Full Text Available Highly pathogenic avian influenza viruses (HPAIV of subtype H5N1 not only cause a devastating disease in domestic chickens and turkeys but also pose a continuous threat to public health. In some countries, H5N1 viruses continue to circulate and evolve into new clades and subclades. The rapid evolution of these viruses represents a problem for virus diagnosis and control. In this work, recombinant vesicular stomatitis virus (VSV vectors expressing HA of subtype H5 were generated. To comply with biosafety issues the G gene was deleted from the VSV genome. The resulting vaccine vector VSV*ΔG(HA was propagated on helper cells providing the VSV G protein in trans. Vaccination of chickens with a single intramuscular dose of 2×10⁸ infectious replicon particles without adjuvant conferred complete protection from lethal H5N1 infection. Subsequent application of the same vaccine strongly boosted the humoral immune response and completely prevented shedding of challenge virus and transmission to sentinel birds. The vaccine allowed serological differentiation of infected from vaccinated animals (DIVA by employing a commercially available ELISA. Immunized chickens produced antibodies with neutralizing activity against multiple H5 viruses representing clades 1, 2.2, 2.5, and low-pathogenic avian influenza viruses (classical clade. Studies using chimeric H1/H5 hemagglutinins showed that the neutralizing activity was predominantly directed against the globular head domain. In summary, these results suggest that VSV replicon particles are safe and potent DIVA vaccines that may help to control avian influenza viruses in domestic poultry.

Asymptomatic ratio for seasonal H1N1 influenza infection among schoolchildren in Taiwan.

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Hsieh, Ying-Hen; Tsai, Chen-An; Lin, Chien-Yu; Chen, Jin-Hua; King, Chwan-Chuen; Chao, Day-Yu; Cheng, Kuang-Fu

2014-02-12

Studies indicate that asymptomatic infections do indeed occur frequently for both seasonal and pandemic influenza, accounting for about one-third of influenza infections. Studies carried out during the 2009 pH1N1 pandemic have found significant antibody response against seasonal H1N1 and H3N2 vaccine strains in schoolchildren receiving only pandemic H1N1 monovalent vaccine, yet reported either no symptoms or only mild symptoms. Serum samples of 255 schoolchildren, who had not received vaccination and had pre-season HI Ab serotiters definition of Fever + (cough or sore throat or nose) + ( headache or pain or fatigue). Asymptomatic ratio for children is found to be substantially higher than that of the general population in literature. In providing reasonable quantification of the asymptomatic infected children spreading pathogens to others in a seasonal epidemic or a pandemic, our estimates of symptomatic ratio of infected children has important clinical and public health implications.

Cross-protection against lethal H5N1 challenge ferrets with an adjuvanted pandemic influenza vaccine

NARCIS (Netherlands)

B. Baras (Benoît); K.J. Stittelaar (Koert); J.H. Simon (James); R.J.M.M. Thoolen (Robert); S.P. Mossman (Sally); F.H. Pistoor (Frank); G. van Amerongen (Geert); M.A. Wettendorff (Martine); E. Hanon (Emmanuel); A.D.M.E. Osterhaus (Albert)

2008-01-01

textabstractBackground. Unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI) of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be

Pandemic influenza (A/H1N1 vaccine uptake among French private general practitioners: a cross sectional study in 2010.

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Pierre Verger

Full Text Available BACKGROUND: In July, 2009, French health authorities, like those in many other countries, decided to embark on a mass vaccination campaign against the pandemic A(H1N1 influenza. Private general practitioners (GPs were not involved in this campaign. We studied GPs' pandemic vaccine (pvaccine uptake, quantified the relative contribution of its potential explanatory factors and studied whether their own vaccination choice was correlated with their recommendations to patients about pvaccination. METHODOLOGY/PRINCIPAL FINDINGS: In this cross-sectional telephone survey, professional investigators interviewed an existing panel of randomly selected private GPs (N = 1431; response rate at inclusion in the panel: 36.8%; participation rate in the survey: 100%. The main outcome variable was GPs' own pvaccine uptake. We used an averaging multi-model approach to quantify the relative contribution of factors associated with their vaccination. The pvaccine uptake rate was 61% (95%CI = 58.3-63.3. Four independent factors contributed the most to this rate (partial Nagelkerke's R(2: history of previous vaccination against seasonal influenza (14.5%, perception of risks and efficacy of the pvaccine (10.8%, opinions regarding the organization of the vaccination campaign (7.1%, and perception of the pandemic's severity (5.2%. Overall, 71.3% (95%CI = 69.0-73.6 of the participants recommended pvaccination to young adults at risk and 40.1% (95%CI = 37.6-42.7 to other young adults. GPs' own pvaccination was strongly predictive of their recommendation to both young adults at risk (OR = 9.6; 95%CI = 7.2-12.6 and those not at risk (OR = 8.5; 95%CI = 6.4-11.4. CONCLUSIONS/SIGNIFICANCE: These results suggest that around 60% of French private GPs followed French authorities' recommendations about vaccination of health care professionals against the A(H1N1 influenza. They pinpoint priority levers for improving preparedness for future influenza pandemics. Besides encouraging GPs

Diversity of the murine antibody response targeting influenza A(H1N1pdm09) hemagglutinin.

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Wilson, Jason R; Tzeng, Wen-Pin; Spesock, April; Music, Nedzad; Guo, Zhu; Barrington, Robert; Stevens, James; Donis, Ruben O; Katz, Jacqueline M; York, Ian A

2014-06-01

We infected mice with the 2009 influenza A pandemic virus (H1N1pdm09), boosted with an inactivated vaccine, and cloned immunoglobulins (Igs) from HA-specific B cells. Based on the redundancy in germline gene utilization, we inferred that between 72-130 unique IgH VDJ and 35 different IgL VJ combinations comprised the anti-HA recall response. The IgH VH1 and IgL VK14 variable gene families were employed most frequently. A representative panel of antibodies were cloned and expressed to confirm reactivity with H1N1pdm09 HA. The majority of the recombinant antibodies were of high avidity and capable of inhibiting H1N1pdm09 hemagglutination. Three of these antibodies were subtype-specific cross-reactive, binding to the HA of A/South Carolina/1/1918(H1N1), and one further reacted with A/swine/Iowa/15/1930(H1N1). These results help to define the genetic diversity of the influenza anti-HA antibody repertoire profile induced following infection and vaccination, which may facilitate the development of influenza vaccines that are more protective and broadly neutralizing. Protection against influenza viruses is mediated mainly by antibodies, and in most cases this antibody response is narrow, only providing protection against closely related viruses. In spite of this limited range of protection, recent findings indicate that individuals immune to one influenza virus may contain antibodies (generally a minority of the overall response) that are more broadly reactive. These findings have raised the possibility that influenza vaccines could induce a more broadly protective response, reducing the need for frequent vaccine strain changes. However, interpretation of these observations is hampered by the lack of quantitative characterization of the antibody repertoire. In this study, we used single-cell cloning of influenza HA-specific B cells to assess the diversity and nature of the antibody response to influenza hemagglutinin in mice. Our findings help to put bounds on the

Perception of the A/H1N1 influenza pandemic and acceptance of influenza vaccination by Université Claude Bernard Lyon 1 staff: A descriptive study.

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Amour, Sélilah; Djhehiche, Khaled; Zamora, Adeline; Bergeret, Alain; Vanhems, Philippe

2015-01-01

We assessed the perception and attitudes of university staff, including medical school and other science specialties, toward the 2009 A/H1N1 influenza pandemic and influenza vaccination program. A cross-sectional online survey was conducted among 4,529 university personnel on October 19-20, 2009. Seven hundred (15%) employees participated in the study. Only 18% were willing to be vaccinated, men more than women (29% versus 9%, P < 0.001), and professors/researchers more than administrative/technical staff (30% vs. 6%, P < 0.001). Intention to be vaccinated was insufficient. Additional efforts are needed to improve information dissemination among university staff. Medical university personnel should receive more information to increase vaccine coverage and protect them as well as patients.

Induction of protective immunity against H1N1 influenza A(H1N1)pdm09 with spray-dried and electron-beam sterilised vaccines in non-human primates.

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Scherließ, Regina; Ajmera, Ankur; Dennis, Mike; Carroll, Miles W; Altrichter, Jens; Silman, Nigel J; Scholz, Martin; Kemter, Kristina; Marriott, Anthony C

2014-04-17

Currently, the need for cooled storage and the impossibility of terminal sterilisation are major drawbacks in vaccine manufacturing and distribution. To overcome current restrictions a preclinical safety and efficacy study was conducted to evaluate new influenza A vaccine formulations regarding thermal resistance, resistance against irradiation-mediated damage and storage stability. We evaluated the efficacy of novel antigen stabilizing and protecting solutions (SPS) to protect influenza A(H1N1)pdm09 split virus antigen under experimental conditions in vitro and in vivo. Original or SPS re-buffered vaccine (Pandemrix) was spray-dried and terminally sterilised by irradiation with 25 kGy (e-beam). Antigen integrity was monitored by SDS-PAGE, dynamic light scattering, size exclusion chromatography and functional haemagglutination assays. In vitro screening experiments revealed a number of highly stable compositions containing glycyrrhizinic acid (GA) and/or chitosan. The most stable composition was selected for storage tests and in vivo assessment of seroconversion in non-human primates (Macaca fascicularis) using a prime-boost strategy. Redispersed formulations with original adjuvant were administered intramuscularly. Storage data revealed high stability of protected vaccines at 4°C and 25°C, 60% relative humidity, for at least three months. Animals receiving original Pandemrix exhibited expected levels of seroconversion after 21 days (prime) and 48 days (boost) as assessed by haemagglutination inhibition and microneutralisation assays. Animals vaccinated with spray-dried and irradiated Pandemrix failed to exhibit seroconversion after 21 days whereas spray-dried and irradiated, SPS-protected vaccines elicited similar seroconversion levels to those vaccinated with original Pandemrix. Boost immunisation with SPS-protected vaccine resulted in a strong increase in seroconversion but had only minor effects in animals treated with non SPS-protected vaccine. In conclusion

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.

GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates.

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Peter T Loudon

2010-06-01

Full Text Available The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a world-wide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99 HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun was analyzed in rhesus macaques.Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particle-mediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine.These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skin-delivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract.

Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

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Hiremath, Jagadish; Kang, Kyung-il; Xia, Ming; Elaish, Mohamed; Binjawadagi, Basavaraj; Ouyang, Kang; Dhakal, Santosh; Arcos, Jesus; Torrelles, Jordi B; Jiang, X; Lee, Chang Won; Renukaradhya, Gourapura J

2016-01-01

Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV). Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.

Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

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Jagadish Hiremath

Full Text Available Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV. Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA nanoparticle (PLGA-NP based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2 chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.

Safety and immunogenicity of an MF59-adjuvanted A/H1N1 pandemic influenza vaccine in children from three to seventeen years of age.

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Knuf, Markus; Leroux-Roels, Geert; Rümke, Hans C; Abarca, Katia; Rivera, Luis; Lattanzi, Maria; Pedotti, Paola; Arora, Ashwani; Kieninger-Baum, Dorothee; Della Cioppa, Giovanni

2015-01-01

This study was designed to identify the optimal dose of an MF59-adjuvanted, monovalent, A/H1N1 influenza vaccine in healthy paediatric subjects. Subjects aged 3-8 years (n=194) and 9-17 years (n=160) were randomized to receive two primary doses of A/H1N1 vaccine containing either 3.75 μg antigen with half a standard dose of MF59 adjuvant, 7.5 μg antigen with a full dose of MF59, or (children 3-8 years only), a non-adjuvanted 15 μg formulation. A booster dose of MF59-adjuvanted seasonal influenza vaccine including homologous A/H1N1 strain was given one year after priming. Immunogenicity was assessed by haemagglutination inhibition (HI) and microneutralization assays. Vaccine safety was assessed throughout the study (up to 18 months). A single priming dose of either MF59-adjuvanted formulation was sufficient to meet the European licensure criteria for pandemic influenza vaccines (HI titres ≥1:40>70%; seroconversion>40%; and GMR>2.5). Two non-adjuvanted vaccine doses were required to meet the same licensure criteria. After first and second doses, percentage of subjects with HI titres ≥1:40 were between 97% and 100% in the adjuvanted vaccine groups compared with 68% and 91% in the non-adjuvanted group, respectively. Postvaccination seroconversion rates ranged from 91% to 98% in adjuvanted groups and were 68% (first dose) and 98% (second dose) in the non-adjuvanted group. HI titres ≥1:330 after primary doses were achieved in 69% to 90% in adjuvanted groups compared with 41% in the non-adjuvanted group. Long-term antibody persistence after priming and a robust antibody response to booster immunization were observed in all vaccination groups. All A/H1N1 vaccine formulations were generally well tolerated. No vaccine-related serious adverse events occurred, and no subjects were withdrawn from the study due to an adverse event. An MF59-adjuvanted influenza vaccine containing 3.75 μg of A/H1N1 antigen was well tolerated and sufficiently immunogenic to meet all the

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

International Nuclear Information System (INIS)

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.

The transmissibility and control of pandemic influenza A (H1N1) virus.

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Yang, Yang; Sugimoto, Jonathan D; Halloran, M Elizabeth; Basta, Nicole E; Chao, Dennis L; Matrajt, Laura; Potter, Gail; Kenah, Eben; Longini, Ira M

2009-10-30

Pandemic influenza A (H1N1) 2009 (pandemic H1N1) is spreading throughout the planet. It has become the dominant strain in the Southern Hemisphere, where the influenza season has now ended. Here, on the basis of reported case clusters in the United States, we estimated the household secondary attack rate for pandemic H1N1 to be 27.3% [95% confidence interval (CI) from 12.2% to 50.5%]. From a school outbreak, we estimated that a typical schoolchild infects 2.4 (95% CI from 1.8 to 3.2) other children within the school. We estimated the basic reproductive number, R0, to range from 1.3 to 1.7 and the generation interval to range from 2.6 to 3.2 days. We used a simulation model to evaluate the effectiveness of vaccination strategies in the United States for fall 2009. If a vaccine were available soon enough, vaccination of children, followed by adults, reaching 70% overall coverage, in addition to high-risk and essential workforce groups, could mitigate a severe epidemic.

Heterologous Prime-Boost Vaccination Using an AS03B-Adjuvanted Influenza A(H5N1) Vaccine in Infants and Children <3 Years of Age

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Nolan, Terry; Izurieta, Patricia; Lee, Bee-Wah; Chan, Poh Chong; Marshall, Helen; Booy, Robert; Drame, Mamadou; Vaughn, David W.

2014-01-01

Background. Protecting young children from pandemic influenza should also reduce transmission to susceptible adults, including pregnant women. Methods. An open study assessed immunogenicity and reactogenicity of a heterologous booster dose of A/turkey/Turkey/1/2005(H5N1)-AS03B (AS03B is an Adjuvant System containing α-tocopherol and squalene in an oil-in-water emulsion [5.93 mg tocopherol]) in infants and children aged 6 to < 36 months that was given 6 months following 2-dose primary vaccination with A/Indonesia/05/2005(H5N1)-AS03B. Vaccines contained 1.9 µg of hemagglutinin antigen and AS03B. Hemagglutinin inhibition (HI) responses, microneutralization titers, and antineuraminidase antibody levels were assessed for 6 months following the booster vaccination. Results. For each age stratum (defined on the basis of the subject's age at first vaccination as 6 to < 12 months, 12 to < 24 months, and 24 to < 36 months) and overall (n = 113), European influenza vaccine licensure criteria were fulfilled for responses to A/turkey/Turkey/1/2005(H5N1) 10 days following the booster vaccination. Local pain and fever increased with consecutive doses. Anamnestic immune responses were demonstrated for HI, neutralizing, and antineuraminidase antibodies against vaccine-homologous/heterologous strains. Antibody responses to vaccine-homologous/heterologous strains persisted in all children 6 months following the booster vaccination. Conclusions. Prevaccination of young children with a clade 2 strain influenza A(H5N1) AS03-adjuvanted vaccine followed by heterologous booster vaccination boosted immune responses to the homologous strain and a related clade, with persistence for at least 6 months. The results support a prime-boost vaccination approach in young children for pandemic influenza preparedness. Clinical Trials Registration. NCT01323946. PMID:24973461

Safety of pandemic H1N1 vaccines in children and adolescents

NARCIS (Netherlands)

E.G. Wijnans (Leonoor); S. de Bie (Sandra); J.P. Dieleman (Jeanne); J. Bonhoeffer (Jan); M.C.J.M. Sturkenboom (Miriam)

2011-01-01

textabstractDuring 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

High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

International Nuclear Information System (INIS)

Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude; Wang, Yue; Liao, Guoyang

2012-01-01

Highlights: ► Vero cell-based HPAI H5N1 vaccine with stable high yield. ► Stable high yield derived from the YNVa H3N2 backbone. ► H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

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

Pandemic influenza A/H1N1 vaccination coverage, adverse reactions, and reasons for vaccine refusal among medical students in Brazil

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Eduardo Pernambuco de Souza

2012-04-01

Full Text Available The aim of this cross-sectional study was to determine, among medical students at a public university in Rio de Janeiro, Brazil, the acceptance of the pandemic influenza A/H1N1 vaccine during the 2010 mass immunization campaign and the vaccine safety in this group and, among unvaccinated students, the reasons for refusing vaccination. Of a total of 858 students, 678 (79% participated in the study. Vaccination coverage was 60.4% among students aged 20 to 39 years (an age group targeted for vaccination and 43.8% among those who did not belong to this age group. The most frequent adverse reactions to the vaccine were pain at the injection site (8.7% and fever (7.9%. There were no serious adverse reactions. Among students aged 20 to 39 years, the most common reasons for refusing the vaccine were "lack of time" (42.4%, "fear of adverse reactions" (41.9%, and "difficult access to the vaccine" (11.5%. Other reasons for vaccine refusal were "uncertainties about vaccine safety and efficacy" and "vaccination was not needed". To increase the acceptance of the influenza vaccine, a comprehensive immunization program should be offered to these students.

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

Safety of pandemic H1N1 vaccines in children and adolescents.

Science.gov (United States)

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.

Silent spread of highly pathogenic Avian Influenza H5N1 virus amongst vaccinated commercial layers

NARCIS (Netherlands)

Poetri, O.N.; Boven, M.; Claassen, I.J.T.M.; Koch, G.; Wibawan, I.W.; Stegeman, A.; Broek, van den J.; Bouma, A.

2014-01-01

The aim of this study was to determine whether a single vaccination of commercial layer type chickens with an inactivated vaccine containing highly pathogenic avian influenza virus strain H5N1 A/chicken/Legok/2003, carried out on the farm, was sufficient to protect against infection with the

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

[Adverse effects of seasonal flu vaccine and new influenza A (H1N1) vaccine in health care workers].

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Torruella, Joan Inglés; Soto, Rosa Gil; Valls, Rosa Carreras; Lozano, Judit Valverde; Carreras, Dolors Benito; Cunillera, Arnau Besora

2013-01-01

To assess and compare adverse effects of Seasonal Influenza Vaccine (SIV) and new Influenza A(H1N1) Vaccine (AIV) in health care workers. Multicenter cross-sectional study in health care workers from acute care hospitals, primary health care centers, social centers, mental health centers and a geriatric hospital participating in the 2009 vaccination campaign. Self-administered questionnaires were sent to all workers vaccinated with SIV and/or AIV. 527 valid questionnaires were collected out of 1123 sent to SIV vaccinated workers (46.9%), and 241 out of 461 sent to AIV vaccinated workers (52.%%). Participant workers include 527 vaccinated only with SIV, 117 first vaccinated with SIV and later with AIV (SIV+AIV), and 125 vaccinated only with AIV. Overall, 18.4% (95%CI 15.1-21.7) of workers vaccinated only with SIV reported adverse effects, as compared to 45.3% (95I 36.3-54.3) reporting adverse effects to AIV in the SIV+AIV group and 46.4% (95%CI 37.7-55.1) of workers vaccinated only with AIV. In all participants the most common adverseeffect was a local reaction. Women wre more reactive to both SIV and AIV than men. In all age groups SIV vaccination alone caused fewer reactions that either AIV only or the combination of SIV+AIV, with the exception of workers below 29 years of age. AIV was associated with more reactions than SIV, with no differences observed in relation to administration sequence. There were differences by sex and age, but reactions always occurred more commonly with AIV. Copyright belongs to the Societat Catalana de Seguretat i Medicina del Treball.

Safety and immunogenicity of 2010-2011 H1N12009-containing trivalent inactivated influenza vaccine in children 12-59 months of age previously given AS03-adjuvanted H1N12009 pandemic vaccine: a PHAC/CIHR Influenza Research Network (PCIRN) study.

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Langley, Joanne M; Scheifele, David W; Quach, Caroline; Vanderkooi, Otto G; Ward, Brian; McNeil, Shelly; Dobson, Simon; Kellner, James D; Kuhn, Susan; Kollman, Tobias; MacKinnon-Cameron, Donna; Smith, Bruce; Li, Yan; Halperin, Scott A

2012-05-14

Concern arose in 2010 that reactogenicity, particularly febrile seizures, to influenza A/H1N1-containing 2010-2011 trivalent seasonal inactivated influenza vaccine (TIV) could occur in young children who had been previously immunized and/or infected with the pandemic strain. We conducted a pre-season study of 2010-2011 TIV safety and immunogenicity in children 12-59 months of age to inform public health decision making. Children immunized with 1 or 2 doses of the pandemic vaccine, with or without the 2009-10 TIV, received 1 or 2 doses of 2010-11 TIV in an observational, multicentre Canadian study. Standard safety monitoring was enhanced by a telephone call at ~24 h post-TIV when adverse events were expected to peak. Summary safety reports were rapidly reported to public health before the launch of public programs. TIV immunogenicity was assessed day 0, and 21 days after final vaccination. Clinical Trials Registration NCT01180621. Among 207 children, a general adverse event was reported by 60.9% of children post-dose one and by 58.3% post-dose two. Only severe fever (>38.5°C) was more common in two-dose compared to one dose recipients (16.7%, n=4 v. 1.0%, n=2). At baseline 99.0% of participants had A/H1N1 hemagglutinin inhibition (HAI) titers ≥10, and 85.5% had a protective titer of ≥40 (95% CI 80.0, 90.0). Baseline geometric mean titers (GMT) were higher in recipients of a 2-dose schedule of pandemic vaccine compared to one-dose recipients: 153.1 (95% CI 126.2, 185.7) v. 78.8 ((58.1, 106.8, pvaccine immunogenicity were exceeded for A/H1N1 and H3N2, but responses to the B antigen were poor. No correlations between reactogenicity and either baseline high influenza titers or serologic response to revaccination were evident. Infants and toddlers who received AS03-adjuvanted A/H1N1 2009 vaccine up to 11 months earlier retained high titers in the subsequent season but re-exposure to A/H1N1 2009 antigen in TIV resulted in no unusual adverse effects and 100% were sero

High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

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Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People' s Republic of China (China); Wang, Yue [National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Yingxin Lane 100, Xicheng District, Beijing 100052, People' s Republic of China (China); Liao, Guoyang [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People' s Republic of China (China)

2012-05-18

Highlights: Black-Right-Pointing-Pointer Vero cell-based HPAI H5N1 vaccine with stable high yield. Black-Right-Pointing-Pointer Stable high yield derived from the YNVa H3N2 backbone. Black-Right-Pointing-Pointer H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

Seroprevalence of influenza A H1N1 and seroconversion of mothers and infants induced by a single dose of monovalent vaccine.

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Chao, Anne; Huang, Yhu-Chering; Chang, Yao-Lung; Wang, Tzu-Hao; Chang, Shuenn-Dyh; Wu, Ting-Shu; Wu, Tsu-Lan; Chao, An-Shine

2013-09-01

To determine the prevalence of preexisting antibodies against the pandemic 2009 Influenza A (H1N1) virus in pregnant women and to evaluate the seroprotection of the mothers and infants by a single injection of monovalent vaccine during the pandemic. Seropositivity rate of H1N1 among the nonvaccinated were compared with the vaccinated women. A single dose of vaccine, either nonadjuvanted AdimFlu-S or MF59-adjuvanted vaccine, was injected to the voluntarily vaccinated group. Maternal and cord blood sera were collected to evaluate the antibody response of the H1N1 virus. Seropositivity was defined as a hemagglutination inhibition titer to H1N1 (A/Taiwan/126/09) ≥ 1:40. A total of 210 healthy, singleton, pregnant women were enrolled between January 2010 and May 2010. Seropositivity (≥ 1:40) of maternal hemagglutination inhibition was significantly higher in the vaccinated group (78%) than the nonvaccinated group (9.5%); 41.6% (20/48) of seropositive titers were >1:80. In nine vaccinated cases resulting in negative serum titers (75% could be achieved in the paired maternal and cord serum samples by a single injection of monovalent H1N1 vaccine. Copyright © 2013. Published by Elsevier B.V.

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

Science.gov (United States)

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

Factors associated with 2009 pandemic influenza A (H1N1 vaccination acceptance among university students from India during the post-pandemic phase

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Thejaswini Venkatesh

2011-07-01

Full Text Available Abstract Background There was a low adherence to influenza A (H1N1 vaccination program among university students and health care workers during the pandemic influenza in many parts of the world. Vaccination of high risk individuals is one of the recommendations of World Health Organization during the post-pandemic period. It is not documented about the student's knowledge, attitude and willingness to accept H1N1 vaccination during the post-pandemic period. We aimed to analyze the student's knowledge, attitude and willingness to accept H1N1 vaccination during the post-pandemic period in India. Methods Vaccine against H1N1 was made available to the students of Vellore Institute of Technology, India from September 2010. The data are based on a cross-sectional study conducted during October 2010 to January 2011 using a self-administered questionnaire with a representative sample of the student population (N = 802. Results Of the 802 respondents, only 102/802 (12.7% had been vaccinated and 105/802 (13% planned to do so in the future, while 595/802 (74% would probably or definitely not get vaccinated in the future. The highest coverage was among the female (65/102, 63.7% and non-compliance was higher among men in the group (384/595; 64.5% (p Conclusions Our study shows that the vaccination coverage among university students remains very low in the post-pandemic period and doubts about the safety and effectiveness of the vaccine are key elements in their rejection. Our results indicate a need to provide accessible information about the vaccine safety by scientific authorities and fill gaps and confusions in this regard.

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.

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.

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines

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Black, Steven; Eskola, Juhani; Siegrist, Claire-Anne; Halsey, Neal; MacDonald, Noni; Law, Barbara; Miller, Elizabeth; Andrews, Nick; Stowe, Julia; Salmon, Daniel; Vannice, Kirsten; Izurieta, Hector S; Akhtar, Aysha; Gold, Mike; Oselka, Gabriel; Zuber, Patrick; Pfeifer, Dina; Vellozzi, Claudia

2010-01-01

Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21·5 cases of Guillain-Barré syndrome and 5·75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86·3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination. PMID:19880172

Immunogenicity and Safety of a Trivalent Inactivated Influenza Vaccine in Children 6 Months to 17 Years of Age, Previously Vaccinated with an AS03-Adjuvanted A(H1N1)Pdm09 Vaccine: Two Open-label, Randomized Trials.

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Vesikari, Timo; Richardus, Jan Hendrik; Berglund, Johan; Korhonen, Tiina; Flodmark, Carl-Erik; Lindstrand, Ann; Silfverdal, Sven Arne; Bambure, Vinod; Caplanusi, Adrian; Dieussaert, Ilse; Roy-Ghanta, Sumita; Vaughn, David W

2015-07-01

During the influenza pandemic 2009-2010, an AS03-adjuvanted A(H1N1)pdm09 vaccine was used extensively in children 6 months of age and older, and during the 2010-2011 influenza season, the A(H1N1)pdm09 strain was included in the seasonal trivalent inactivated influenza vaccine (TIV) without adjuvant. We evaluated the immunogenicity and safety of TIV in children previously vaccinated with the AS03-adjuvanted A(H1N1)pdm09 vaccine. Healthy children were randomized (1:1) to receive TIV or a control vaccine. Children were aged 6 months to 9 years (n = 154) and adolescents 10-17 years (n = 77) when they received AS03-adjuvanted A(H1N1)pdm09 vaccine at least 6 months before study enrolment. Hemagglutination inhibition (HI) and neutralizing antibody responses against the A(H1N1)pdm09 strain were evaluated before (day 0) and at day 28 and month 6 after study vaccination. Reactogenicity was assessed during the 7 day postvaccination period, and safety was assessed for 6 months. At day 0, >93.9% of all children had HI titers ≥1:40 for the A(H1N1)pdm09 strain, which increased to 100% at both day 28 and month 6 in the TIV group. Between days 0 and 28, HI antibody geometric mean titers against A(H1N1)pdm09 increased by 9-fold and 4-fold in children 6 months to 9 years of age and 10-17 years of age, respectively. AS03-adjuvanted A(H1N1)pdm09 vaccine-induced robust immune responses in children that persisted into the next season, yet were still boosted by TIV containing A(H1N1)pdm09. The reactogenicity and safety profile of TIV did not appear compromised by prior receipt of AS03-adjuvanted A(H1N1)pdm09 vaccine.

Duration of (18)F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination

DEFF Research Database (Denmark)

Thomassen, Anders; Lerberg Nielsen, Anne; Gerke, Oke

2011-01-01

PURPOSE: The aim of our study was to investigate the occurrence of fluorodeoxyglucose (FDG) avidity in draining axillary lymph nodes after vaccination against influenza (H1N1v pandemic and seasonal) and to determine the period of increased FDG uptake. METHODS: During December 2009, patients...

The use of the health belief model to assess predictors of intent to receive the novel (2009 H1N1 influenza vaccine

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Jean-Venable “Kelly” R.Goode, PharmD, BCPS, FAPhA, FCCP

2012-01-01

Full Text Available Objectives: 1 Assess participants’ perceptions of severity, risk, and susceptibility to the novel H1N1 influenza virus and/or vaccine, vaccine benefits and barriers, and cues to action and 2 Identify predictors of participants’ intention to receive the novel H1N1 vaccine.Design: Cross-sectional, descriptive studySetting: Local grocery store chain and university in the central Virginia areaParticipants: Convenience sample of adult college students and grocery store patronsIntervention: Participants filled out an anonymous, self-administered questionnaire based upon the Health Belief Model.Main Outcome Measures: Participants’ predictors of intention to receive the novel H1N1 vaccineResults: A total of 664 participants completed a questionnaire. The majority of participants were aged 25-64 years old (66.9%. The majority were female (69.1%, Caucasian (73.7%, and felt at risk for getting sick from the virus (70.3%. Most disagreed that they would die from the virus (68.0%. Participants received novel H1N1 vaccine recommendations from their physicians (28.2%, pharmacists (20.7%, and nurses (16.1%. The majority intended to receive the H1N1 vaccine (58.1%. Participants were significantly more likely to intend to receive the H1N1 vaccine if they had lower scores on the perceived vaccine barriers domain (OR= 0.57, CI: 0.35-0.93. Physicians’ recommendations (OR=0.26, CI: 0.11-0.62 and 2008 seasonal flu vaccination (OR=0.45, CI: 0.24-0.83 were significant predictors of intention to receive the H1N1 vaccine.Conclusions: Most participants felt at risk for getting the novel H1N1 virus and intended to receive the novel H1N1 vaccine. Educating patients about vaccine benefits and increasing healthcare professionals' vaccine recommendations may increase vaccination rates in future pandemics.

Association between the 2008-09 seasonal influenza vaccine and pandemic H1N1 illness during Spring-Summer 2009: four observational studies from Canada.

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Danuta M Skowronski

2010-04-01

Full Text Available In late spring 2009, concern was raised in Canada that prior vaccination with the 2008-09 trivalent inactivated influenza vaccine (TIV was associated with increased risk of pandemic influenza A (H1N1 (pH1N1 illness. Several epidemiologic investigations were conducted through the summer to assess this putative association.(1 test-negative case-control design based on Canada's sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2 conventional case-control design using population controls in Quebec; (3 test-negative case-control design in Ontario; and (4 prospective household transmission (cohort study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008-09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33-0.59. In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases.Prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009 in Canada. The occurrence of bias (selection, information or

US school morbidity and mortality, mandatory vaccination, institution closure, and interventions implemented during the 2009 influenza A H1N1 pandemic.

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Rebmann, Terri; Elliott, Michael B; Swick, Zachary; Reddick, David

2013-03-01

The 2009 H1N1 pandemic disproportionately affected school-aged children, but only school-based outbreak case studies have been conducted. The purposes of this study were to evaluate US academic institutions' experiences during the 2009 H1N1 pandemic in terms of infection prevention interventions implemented and to examine factors associated with school closure during the pandemic. An online survey was sent to school nurses in May through July 2011. Hierarchical logistic regressions were used to determine predictive models for having a mandatory H1N1 vaccination policy for school nurses and school closure. In all, 1,997 nurses from 26 states participated. Very few nurses (3.3%, n=65) reported having a mandatory H1N1 influenza vaccination policy; nurses were more likely than all other school employees (pnurse employed by a public health agency or hospital, and being a private school. The most commonly implemented interventions included encouraging staff and students to exercise hand hygiene and increasing classroom cleaning; least commonly implemented interventions included discouraging face-to-face meetings, training staff on H1N1 influenza and/or respiratory hygiene, and discouraging handshaking. Schools should develop and continue to improve their pandemic plans, including collaborating with community response agencies.

Isolation of avian influenza H5N1 virus from vaccinated commercial layer flock in Egypt

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El-Zoghby Elham F

2012-11-01

Full Text Available Abstract Background Uninterrupted transmission of highly pathogenic avian influenza virus (HPAIV H5N1 of clade 2.2.1 in Egypt since 2006 resulted in establishment of two main genetic clusters. The 2.2.1/C group where all recent human and majority of backyard origin viruses clustered together, meanwhile the majority of viruses derived from vaccinated poultry in commercial farms grouped in 2.2.1.1 clade. Findings In the present investigation, an HPAIV H5N1 was isolated from twenty weeks old layers chickens that were vaccinated with a homologous H5N1 vaccine at 1, 7 and 16 weeks old. At twenty weeks of age, birds showed cyanosis of comb and wattle, decrease in egg production and up to 27% mortality. Examined serum samples showed low antibody titer in HI test (Log2 3.2± 4.2. The hemagglutinin (HA and neuraminidase (NA genes of the isolated virus were closely related to viruses in 2.2.1/C group isolated from poultry in live bird market (LBM and backyards or from infected people. Conspicuous mutations in the HA and NA genes including a deletion within the receptor binding domain in the HA globular head region were observed. Conclusions Despite repeated vaccination of layer chickens using a homologous H5N1 vaccine, infection with HPAIV H5N1 resulted in significant morbidity and mortality. In endemic countries like Egypt, rigorous control measures including enforcement of biosecurity, culling of infected birds and constant update of vaccine virus strains are highly required to prevent circulation of HPAIV H5N1 between backyard birds, commercial poultry, LBM and humans.

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.

A novel H6N1 virus-like particle vaccine induces long-lasting cross-clade antibody immunity against human and avian H6N1 viruses.

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Yang, Ji-Rong; Chen, Chih-Yuan; Kuo, Chuan-Yi; Cheng, Chieh-Yu; Lee, Min-Shiuh; Cheng, Ming-Chu; Yang, Yu-Chih; Wu, Chia-Ying; Wu, Ho-Sheng; Liu, Ming-Tsan; Hsiao, Pei-Wen

2016-02-01

Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In this study, we engineered a recombinant H6N1 virus-like particle (VLP) and investigated its vaccine effectiveness compared to the traditional egg-based whole inactivated virus (WIV) vaccine. The H6N1-VLPs exhibited similar morphology and functional characteristics to influenza viruses. Prime-boost intramuscular immunization in mice with unadjuvanted H6N1-VLPs were highly immunogenic and induced long-lasting antibody immunity. The functional activity of the VLP-elicited IgG antibodies was proved by in vitro seroprotective hemagglutination inhibition and microneutralization titers against the homologous human H6N1 virus, as well as in vivo viral challenge analyses which showed H6N1-VLP immunization significantly reduced viral load in the lung, and protected against human H6N1 virus infection. Of particular note, the H6N1-VLPs but not the H6N1-WIVs were able to confer cross-reactive humoral immunity; antibodies induced by H6N1-VLP vaccine robustly inhibited the hemagglutination activities and in vitro replication of distantly-related heterologous avian H6N1 viruses. Furthermore, the H6N1-VLPs were found to elicit significantly greater anti-HA2 antibody responses in immunized mice than H6N1-WIVs. Collectively, we demonstrated for the first time a novel H6N1-VLP vaccine that effectively provides broadly protective immunity against both human and avian H6N1 viruses. These results, which uncover the underlying mechanisms for induction of wide-range immunity against influenza viruses, may be useful for future influenza vaccine development. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Influenza A (H1N1) organising pneumonia.

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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.

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.

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.

Pandemic (H1N1 2009 Influenza Virus Infection in A Survivor who has recovered from severe H7N9 Virus Infection, China

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Shan-Hui Chen

2016-10-01

Full Text Available We firstly report a patient who presented with severe complications after infection with influenza A(H1N1 pdm2009, more than one year after recovery from severe H7N9 virus infections. The population of patients who recovered from severe H7N9 infections might be at a higher risk to suffer severe complications after seasonal influenza infections, and they should be included in the high-risk populations recommended to receive seasonal influenza vaccination.

Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccine: Multinational case-control study in Europe

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J.P. Dieleman (Jeanne); S. Romio (Silvana); K. Johansen (Kari); D.M. Weibel (Daniel); J. Bonhoeffer (Jan); M.C.J.M. Sturkenboom (Miriam)

2011-01-01

textabstractObjective: To assess the association between pandemic influenza A (H1N1) 2009 vaccine and Guillain-Barré syndrome. Design: Case-control study. Setting: Five European countries. Participants: 104 patients with Guillain-Barré syndrome and its variant Miller-Fisher syndrome matched to one

Intercontinental circulation of human influenza A(H1N2) reassortant viruses during the 2001-2002 influenza season.

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Xu, Xiyan; Smith, Catherine B; Mungall, Bruce A; Lindstrom, Stephen E; Hall, Henrietta E; Subbarao, Kanta; Cox, Nancy J; Klimov, Alexander

2002-11-15

Reassortant influenza A viruses bearing the H1 subtype of hemagglutinin (HA) and the N2 subtype of neuraminidase (NA) were isolated from humans in the United States, Canada, Singapore, Malaysia, India, Oman, Egypt, and several countries in Europe during the 2001-2002 influenza season. The HAs of these H1N2 viruses were similar to that of the A/New Caledonia/20/99(H1N1) vaccine strain both antigenically and genetically, and the NAs were antigenically and genetically related to those of recent human H3N2 reference strains, such as A/Moscow/10/99(H3N2). All 6 internal genes of the H1N2 reassortants examined originated from an H3N2 virus. This article documents the first widespread circulation of H1N2 reassortants on 4 continents. The current influenza vaccine is expected to provide good protection against H1N2 viruses, because it contains the A/New Caledonia/20/99(H1N1) and A/Moscow/10/99(H3N2)-like viruses, which have H1 and N2 antigens that are similar to those of recent H1N2 viruses.

Guillain-Barré syndrome following receipt of influenza A (H1N1) 2009 monovalent vaccine in Korea with an emphasis on Brighton Collaboration case definition.

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Choe, Young June; Cho, Heeyeon; Bae, Geun-Ryang; Lee, Jong-Koo

2011-03-03

In 2009-2010 season, with ongoing of influenza A (H1N1), employment of mass vaccination has generated concerns in issue of adverse events following immunization (AEFI). This study investigates the clinical and laboratory data of reported cases of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) following receipt of influenza A (H1N1) 2009 monovalent vaccine to the National Vaccine Injury Compensation Program (NVICP) in Korea, with all cases reviewed under case definition developed by Brighton Collaboration GBS Working Group. Retrospective review of medical records for all suspected cases of GBS ad FS following receipt of influenza A (H1N1) monovalent vaccine reported to NVICP from December 1, 2009, through April 28, 2010 was conducted. Additional analyses were performed for identification of levels of diagnostic certainty according to Brighton Collaboration case definition. Of 29 reported cases, 22 were confirmed to meet Brighton criteria level 1, 2, or 3 for GBS (21) or FS (1). Of those, 2 (9.1%) met level 1, 9 (40.9%) met level 2, and 11 (50.0%) met level 3. The male to female ratio was 2:0 in cases with level 1, 8:1 in cases with level 2, and 3:8 in cases with level 3. The mean age was older in cases with level 1 (54.0 ± 26.9) than that of cases with level 2 (25.6 ± 22.8), and level 3 (13.6 ± 2.4, P=0.005). The median onset interval was longer in cases with level 1 (16 days) than that of cases that met level 2 (12.44 days), and 3 (1.09 days, P=0.019). The Brighton case definition was used to improve the quality of AEFI data in Korea, and was applicable in retrospective review of medical records in cases with GBS and FS after influenza A (H1N1) vaccination. These findings suggest that standardized case definition was feasible in clarifying the AEFI data, and to further increase the understanding of possible relationship of influenza vaccine and GBS. Copyright © 2011 Elsevier Ltd. All rights reserved.

Determinants of non-vaccination against pandemic 2009 H1N1 influenza in pregnant women: a prospective cohort study.

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Romain Freund

Full Text Available BACKGROUND: In October 2009, the French government organized a national-wide, free of charge vaccination campaign against pandemic H1N1 influenza virus, especially targeting pregnant women, a high risk group for severe illness. The study objective was to evaluate pandemic flu vaccine uptake and factors associated with non-vaccination in a population of pregnant women. METHODOLOGY/PRINCIPAL FINDINGS: In a prospective cohort conducted in 3 maternity hospitals in Paris, 882 pregnant women were randomly included between October 12, 2009 and February 3, 2010, with the aim to study characteristics of pandemic influenza during pregnancy. At inclusion, socio-demographic, medical, obstetrical factors and those associated with a higher risk of flu exposition and disease-spreading were systematically collected. Pandemic flu vaccine uptake was checked until delivery. 555 (62.9% women did not get vaccinated. Determinants associated with non-vaccination in a multivariate logistic regression were: geographic origin (Sub-Saharan African origin, adjusted Odd Ratio aOR = 5.4[2.3-12.7], North African origin, aOR = 2.5[1.3-4.7] and Asian origin, aOR = 2.1[1.7-2.6] compared to French and European origin and socio-professional categories (farmers, craftsmen and tradesmen, aOR = 2.3[2.0-2.6], intermediate professionals, aOR = 1.3[1.0-1.6], employees and manual workers, aOR = 2.5[1.4-4.4] compared to managers and intellectual professionals. The probability of not receiving pandemic flu vaccine was lower among women vaccinated against seasonal flu in the previous 5 years (aOR = 0.6[0.4-0.8] and among those who stopped smoking before or early during pregnancy (aOR = 0.6[0.4-0.8]. Number of children less than 18 years old living at home, work in contact with children or in healthcare area, or professional contact with the public, were not associated with a higher vaccine uptake. CONCLUSIONS/SIGNIFICANCE: In this cohort of pregnant women, vaccine coverage against pandemic

An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses

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Chan Chris CS

2010-01-01

Full Text Available Abstract Background A growing concern has raised regarding the pandemic potential of the highly pathogenic avian influenza (HPAI H5N1 viruses. Consequently, there is an urgent need to develop an effective and safe vaccine against the divergent H5N1 influenza viruses. In the present study, we designed a tetra-branched multiple antigenic peptide (MAP-based vaccine, designated M2e-MAP, which contains the sequence overlapping the highly conserved extracellular domain of matrix protein 2 (M2e of a HPAI H5N1 virus, and investigated its immune responses and cross-protection against different clades of H5N1 viruses. Results Our results showed that M2e-MAP vaccine induced strong M2e-specific IgG antibody responses following 3-dose immunization of mice with M2e-MAP in the presence of Freunds' or aluminium (alum adjuvant. M2e-MAP vaccination limited viral replication and attenuated histopathological damage in the challenged mouse lungs. The M2e-MAP-based vaccine protected immunized mice against both clade1: VN/1194 and clade2.3.4: SZ/406H H5N1 virus challenge, being able to counteract weight lost and elevate survival rate following lethal challenge of H5N1 viruses. Conclusions These results suggest that M2e-MAP presenting M2e of H5N1 virus has a great potential to be developed into an effective subunit vaccine for the prevention of infection by a broad spectrum of HPAI H5N1 viruses.

Influenza A (H1N1) neuraminidase inhibitors from Vitis amurensis

DEFF Research Database (Denmark)

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...

Phase 1 study of pandemic H1 DNA vaccine in healthy adults.

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Michelle C Crank

Full Text Available A novel, swine-origin influenza A (H1N1 virus was detected worldwide in April 2009, and the World Health Organization (WHO declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1 influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1 licensed monovalent inactivated vaccine (MIV.20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry.Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine.H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.Clinicaltrials.gov NCT00973895.

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.

A study of side-effects of Pandemrix® influenza (H1N1) vaccine on board a Norwegian naval vessel.

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Munch, Johan Storm; Johnsen, Bjørn Helge; Birkeland, Ingelin; Finne, Morten; Utkilen, Torun; Bøe, Tommy; Mjølhus, Gry; Sommerfelt-Pettersen, Jan

2010-01-01

The frigate His Norwegian Majesty's ship (HNoMS) Fridtjof Nansen was participating in operations in the Gulf of Aden in support of the EU mission tasked with protecting vessels from the threat of piracy. The crew was therefore prioritized and given the first batch of Influenza A (H1N1) vaccine (Pandemrix(®)). To investigate the type, frequency, and intensity of side effects after whole-crew vaccination with Pandemrix vaccine in healthy subjects in a controlled environment. A hundred and thirty-three members of the crew were vaccinated, and then they participated in the study. The side effects of the vaccination were evaluated through a survey. Seventy-five per cent of the vaccinated sailors reported adverse reactions to the vaccine, with 9% not being able to perform their daily duties for one day. Muscle pain, headaches, malaise, and fatigue were the most frequent symptoms reported. The vaccination program using Pandemrix H1N1 vaccine resulted in a high rate of side effects, which were generally mild and resolved within a few days. No serious lasting side effects of the vaccination were reported or registered. The adverse effects of the vaccination did not affect the operational capacity of the vessel.

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

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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.

Outbreak of pandemic influenza A/H1N1 2009 in Nepal.

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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.

Computational Identification of Antigenicity-Associated Sites in the Hemagglutinin Protein of A/H1N1 Seasonal Influenza Virus.

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Xiaowei Ren

Full Text Available The antigenic variability of influenza viruses has always made influenza vaccine development challenging. The punctuated nature of antigenic drift of influenza virus suggests that a relatively small number of genetic changes or combinations of genetic changes may drive changes in antigenic phenotype. The present study aimed to identify antigenicity-associated sites in the hemagglutinin protein of A/H1N1 seasonal influenza virus using computational approaches. Random Forest Regression (RFR and Support Vector Regression based on Recursive Feature Elimination (SVR-RFE were applied to H1N1 seasonal influenza viruses and used to analyze the associations between amino acid changes in the HA1 polypeptide and antigenic variation based on hemagglutination-inhibition (HI assay data. Twenty-three and twenty antigenicity-associated sites were identified by RFR and SVR-RFE, respectively, by considering the joint effects of amino acid residues on antigenic drift. Our proposed approaches were further validated with the H3N2 dataset. The prediction models developed in this study can quantitatively predict antigenic differences with high prediction accuracy based only on HA1 sequences. Application of the study results can increase understanding of H1N1 seasonal influenza virus antigenic evolution and accelerate the selection of vaccine strains.

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.

Suboptimal protection against H5N1 highly pathogenic avian influenza viruses from Vietnam in ducks vaccinated with commercial poultry vaccines.

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Cha, Ra Mi; Smith, Diane; Shepherd, Eric; Davis, C Todd; Donis, Ruben; Nguyen, Tung; Nguyen, Hoang Dang; Do, Hoa Thi; Inui, Ken; Suarez, David L; Swayne, David E; Pantin-Jackwood, Mary

2013-10-09

Domestic ducks are the second most abundant poultry species in many Asian countries including Vietnam, and play a critical role in the epizootiology of H5N1 highly pathogenic avian influenza (HPAI) [FAO]. In this study, we examined the protective efficacy in ducks of two commercial H5N1 vaccines widely used in Vietnam; Re-1 containing A/goose/Guangdong/1/1996 hemagglutinin (HA) clade 0 antigens, and Re-5 containing A/duck/Anhui/1/2006 HA clade 2.3.4 antigens. Ducks received two doses of either vaccine at 7 and at 14 or 21 days of age followed by challenge at 30 days of age with viruses belonging to the HA clades 1.1, 2.3.4.3, 2.3.2.1.A and 2.3.2.1.B isolated between 2008 and 2011 in Vietnam. Ducks vaccinated with the Re-1 vaccine were protected after infection with the two H5N1 HPAI viruses isolated in 2008 (HA clades 1.1 and 2.3.4.3) showing no mortality and limited virus shedding. The Re-1 and Re-5 vaccines conferred 90-100% protection against mortality after challenge with the 2010 H5N1 HPAI viruses (HA clade 2.3.2.1.A); but vaccinated ducks shed virus for more than 7 days after challenge. Similarly, the Re-1 and Re-5 vaccines only showed partial protection against the 2011 H5N1 HPAI viruses (HA clade 2.3.2.1.A and 2.3.2.1.B), with a high proportion of vaccinated ducks shedding virus for more than 10 days. Furthermore, 50% mortality was observed in ducks vaccinated with Re-1 and challenged with the 2.3.2.1.B virus. The HA proteins of the 2011 challenge viruses had the greatest number of amino acid differences from the two vaccines as compared to the viruses from 2008 and 2009, which correlates with the lesser protection observed with these viruses. These studies demonstrate the suboptimal protection conferred by the Re-1 and Re-5 commercial vaccines in ducks against H5N1 HPAI clade 2.3.2.1 viruses, and underscore the importance of monitoring vaccine efficacy in the control of H5N1 HPAI in ducks. Published by Elsevier Ltd.

Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza

OpenAIRE

Rosas, Cristina; Van de Walle, Gerlinde R.; Metzger, Stephan M.; Hoelzer, Karin; Dubovi, Edward J.; Kim, Sung G.; Parrish, Colin R.; Osterrieder, Nikolaus

2008-01-01

In 2004, canine influenza virus (CIV) was identified as a respiratory pathogen of dogs for the first time and is closely related to H3N8 equine influenza virus (EIV). We generated a recombinant vectored vaccine that expresses H3 of a recent isolate of EIV using equine herpesvirus type 1 (EHV-1) as the delivery vehicle. This EHV-1 vectored vaccine exhibited robust and stable EIV H3 expression and induced a strong influenza virus-specific response in both mice and dogs upon intranasal or subcut...

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 ...

Risk of Guillain-Barré syndrome after exposure to pandemic influenza A(H1N1)pdm09 vaccination or infection: a Norwegian population-based cohort study.

Science.gov (United States)

Ghaderi, Sara; Gunnes, Nina; Bakken, Inger Johanne; Magnus, Per; Trogstad, Lill; Håberg, Siri Eldevik

2016-01-01

Vaccinations and infections are possible triggers of Guillain-Barré syndrome (GBS). However, studies on GBS after vaccinations during the influenza A(H1N1)pmd09 pandemic in 2009, show inconsistent results. Only few studies have addressed the role of influenza infection. We used information from national health data-bases with information on the total Norwegian population (N = 4,832,211). Cox regression analyses with time-varying covariates and self-controlled case series was applied. The risk of being hospitalized with GBS during the pandemic period, within 42 days after an influenza diagnosis or pandemic vaccination was estimated. There were 490 GBS cases during 2009-2012 of which 410 cases occurred after October 1, 2009 of which 46 new cases occurred during the peak period of the influenza pandemic. An influenza diagnosis was registered for 2.47% of the population and the vaccination coverage was 39.25%. The incidence rate ratio of GBS during the pandemic peak relative to other periods was 1.46 [95% confidence interval (CI) 1.08-1.98]. The adjusted hazard ratio (HR) of GBS within 42 days after a diagnosis of pandemic influenza was 4.89 (95% CI 1.17-20.36). After pandemic vaccination the adjusted HR was 1.11 (95% CI 0.51-2.43). Our results indicated that there was a significantly increased risk of GBS during the pandemic season and after pandemic influenza infection. However, vaccination did not increase the risk of GBS. The small number of GBS cases in this study warrants caution in the interpretation of the findings.

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.

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

Safety and immunogenicity of a modified-vaccinia-virus-Ankara-based influenza A H5N1 vaccine: a randomised, double-blind phase 1/2a clinical trial.

Science.gov (United States)

Kreijtz, Joost H C M; Goeijenbier, Marco; Moesker, Fleur M; van den Dries, Lennert; Goeijenbier, Simone; De Gruyter, Heidi L M; Lehmann, Michael H; Mutsert, Gerrie de; van de Vijver, David A M C; Volz, Asisa; Fouchier, Ron A M; van Gorp, Eric C M; Rimmelzwaan, Guus F; Sutter, Gerd; Osterhaus, Albert D M E

2014-12-01

Modified vaccinia virus Ankara (MVA) is a promising viral vector platform for the development of an H5N1 influenza vaccine. Preclinical assessment of MVA-based H5N1 vaccines showed their immunogenicity and safety in different animal models. We aimed to assess the safety and immunogenicity of the MVA-haemagglutinin-based H5N1 vaccine MVA-H5-sfMR in healthy individuals. In a single-centre, double-blind phase 1/2a study, young volunteers (aged 18-28 years) were randomly assigned with a computer-generated list in equal numbers to one of eight groups and were given one injection or two injections intramuscularly at an interval of 4 weeks of a standard dose (10(8) plaque forming units [pfu]) or a ten times lower dose (10(7) pfu) of the MVA-H5-sfMR (vector encoding the haemagglutinin gene of influenza A/Vietnam/1194/2004 virus [H5N1 subtype]) or MVA-F6-sfMR (empty vector) vaccine. Volunteers and physicians who examined and administered the vaccine were masked to vaccine assignment. Individuals who received the MVA-H5-sfMR vaccine were eligible for a booster immunisation 1 year after the first immunisation. Primary endpoint was safety. Secondary outcome was immunogenicity. The trial is registered with the Dutch Trial Register, number NTR3401. 79 of 80 individuals who were enrolled completed the study. No serious adverse events were identified. 11 individuals reported severe headache and lightheadedness, erythema nodosum, respiratory illness (accompanied by influenza-like symptoms), sore throat, or injection-site reaction. Most of the volunteers had one or more local (itch, pain, redness, and swelling) and systemic reactions (rise in body temperature, headache, myalgia, arthralgia, chills, malaise, and fatigue) after the first, second, and booster immunisations. Individuals who received the 10(7) dose had fewer systemic reactions. The MVA-H5-sfMR vaccine at 10(8) pfu induced significantly higher antibody responses after one and two immunisations than did 10(7) pfu when

Estimation of transmission parameters of H5N1 avian influenza virus in chickens.

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Annemarie Bouma

2009-01-01

Full Text Available Despite considerable research efforts, little is yet known about key epidemiological parameters of H5N1 highly pathogenic influenza viruses in their avian hosts. Here we show how these parameters can be estimated using a limited number of birds in experimental transmission studies. Our quantitative estimates, based on Bayesian methods of inference, reveal that (i the period of latency of H5N1 influenza virus in unvaccinated chickens is short (mean: 0.24 days; 95% credible interval: 0.099-0.48 days; (ii the infectious period of H5N1 virus in unvaccinated chickens is approximately 2 days (mean: 2.1 days; 95%CI: 1.8-2.3 days; (iii the reproduction number of H5N1 virus in unvaccinated chickens need not be high (mean: 1.6; 95%CI: 0.90-2.5, although the virus is expected to spread rapidly because it has a short generation interval in unvaccinated chickens (mean: 1.3 days; 95%CI: 1.0-1.5 days; and (iv vaccination with genetically and antigenically distant H5N2 vaccines can effectively halt transmission. Simulations based on the estimated parameters indicate that herd immunity may be obtained if at least 80% of chickens in a flock are vaccinated. We discuss the implications for the control of H5N1 avian influenza virus in areas where it is endemic.