H5N1 influenza: A protean pandemic threat

Guan, Yi; Poon, Leo L. M.; Cheung, Chung Yan; Ellis, T.M.; Lim, Wilina; Lipatov, A. S.; Chan, KH; Sturm‐Ramirez, Katharine; Cheung, CY; Leung, Connie Y. H.; Yuen, Kwok‐Yung; Webster, Robert G.; Peiris, Malik

doi:10.1073/pnas.0402443101

Cited by 363 publications

(314 citation statements)

References 25 publications

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“…Our data indicate that the candidate whole virus vaccine has the potential to be effective against a broad range of H5N1 viruses. Antisera generated by immunization with the VN1203 vaccine, prepared using the clade 1 strain Vietnam/1203/2002, not only neutralized a number of H5N1 clade 1 strains ranging from 1997 to 2004 isolates (differing in HA antigenicity [23][24][25]) but also neutralized the first clade 2 strain to emerge (Indonesia/05/2005) [15]. The baculovirus-derived recombinant HA antigen was less effective in inducing neutralizing antibodies against the clade 1 strains, and it did not induce neutralizing responses to the clade 2 strain, in agreement with reports that very high antigen doses of rHA were required to induce seroconversion in humans [16].…”

Section: Discussionmentioning

confidence: 99%

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Kistner

Howard

Spruth

et al. 2007

Vaccine

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The rapid spread and the transmission to humans of avian influenza virus (H5N1) has induced worldwide fears of a new pandemic and raised concerns over the ability of standard influenza vaccine production methods to rapidly supply sufficient amounts of an effective vaccine. We report here on a robust and flexible strategy which uses wild-type virus grown in a continuous cell culture (Vero) system to produce an inactivated whole virus vaccine. Candidate vaccines based on clade 1 and clade 2 influenza H5N1 strains were developed and demonstrated to be highly immunogenic in animal models. The vaccines induce cross-neutralising antibodies, highly cross-reactive T-cell responses and are protective in a mouse challenge model not only against the homologous virus but against other H5N1 strains, including those from another clade. These data indicate that cell culture-grown, whole virus vaccines, based on the wild-type virus, allow the rapid high yield production of a candidate pandemic vaccine.

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Section: Discussionmentioning

confidence: 99%

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Kistner

Howard

Spruth

et al. 2007

Vaccine

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“…Some virus strains may be resistant to the antiviral effects of proinflammatory cytokines and ⁄ or result in their increased production [7], with a consequent increase in disease severity. While it may be possible to upgrade some general acute beds to provide Level 2 care, and some Level 2 beds to accept mechanically ventilated patients, these approaches are crucially dependent on the availability of trained staff.…”

Section: Discussionmentioning

confidence: 99%

Modelling the impact of an influenza pandemic on critical care services in England

2005

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SummaryThe UK Influenza Pandemic Contingency Plan does not consider the impact of a pandemic on critical care services. We modelled the demand for critical care beds in England with software developed by the Centers for Disease Control (FLUSURGE 1.0), using a range of attack rates and pandemic durations. Using inputs that have been employed in UK Department of Health scenarios (25% attack rate and 8-week pandemic duration) resulted in a demand for ventilatory support that exceeded 200% of present capacity. Demand remained unsustainably high even when more favourable scenarios were considered. Current critical care bed capacity in England would be unable to cope with the increased demand provided by an influenza pandemic. Appropriate contingency planning is essential. There is general agreement regarding the increasing threat of a fresh influenza epidemic [1]. Despite public health measures, an epidemic will result in an increased number of admissions, both to hospitals and to intensive care units (ICUs). The recent Influenza Pandemic Plan from the UK Department of Health [1] addresses many aspects of an influenza pandemic, but provides no estimate of the likely impact on critical care services. We have tried to quantify the probable demands on critical care services in a UK setting by modelling the requirement for intensive care admission to ICUs in England, using a software program (FLUSURGE 1.0) developed at the Centers for Disease Control in the USA [2]. MethodsWe used FLUSURGE 1.0 [2] to calculate the impact of an influenza pandemic in England on hospital admission, occupancy of all ICU beds, and of Level 3 beds (i.e. those with facilities for mechanical ventilation). Data on population (49.97 million) and age distribution [3], acute hospital beds (109 846) [4], and intensive care bed numbers (1787) [5] were obtained from publicly available sources. We initially modelled demand based on an 8-week epidemic and a 25% attack rate, but also assessed the sensitivity of our estimates to variations in these figures. Simulations were also constructed using the assumptions that either half or all of the high dependency (or Level 2) beds (1426) [5] could be upgraded to Level 3 intensive care beds in the event of a pandemic. The age distribution bins in UK data [3] meant that we had to use the population under 19 years to provide figures for the lowest population bin in FLUSURGE 1.0 (less than 16 years) [2]. All other inputs were available without modification. We also considered the impact of neuraminidase inhibitors, which may reduce disease duration by approximately 1-2 days [6]. Their impact on disease severity is less clear, but the incidence of hospitalisation and complications requiring antibiotic therapy may be reduced by 50% [6]. ResultsThe simulation with an 8-week epidemic and 25% attack rate resulted in a peak weekly hospital admission rate of 35,738, and a peak daily hospital admission rate Anaesthesia, 2005, 60, pages 952-954

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“…Additionally, more than 420,000 cases were reported to be caused by the 2009 swine flu (H1N1) outbreak (32). In addition to the annual threat posed by seasonal influenza virus strains, avian influenza virus strains are now posing a potential threat to the human population (18). All of these facts argue for improved approaches to preventing influenza virus infections.…”

mentioning

confidence: 99%

Intranasal Immunization of Ferrets with Commercial Trivalent Influenza Vaccines Formulated in a Nanoemulsion-Based Adjuvant

Hamouda

Sutcliffe

Ciotti

et al. 2011

Clin Vaccine Immunol

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H5N1 influenza: A protean pandemic threat

Abstract: influenza A ͉ human ͉ avian ͉ virus evolution ͉ cytokine

Cited by 363 publications

References 25 publications

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Modelling the impact of an influenza pandemic on critical care services in England

Intranasal Immunization of Ferrets with Commercial Trivalent Influenza Vaccines Formulated in a Nanoemulsion-Based Adjuvant

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