Transmission of influenza A/H5N1 viruses in mammals

Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan.
Virus Research (Impact Factor: 2.32). 08/2013; 178(1). DOI: 10.1016/j.virusres.2013.07.017
Source: PubMed


Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans and cause severe respiratory disease and fatalities. Currently, these viruses are not efficiently transmitted from person to person, although limited human-to-human transmission may have occurred. Nevertheless, further adaptation of avian H5N1 influenza A viruses to humans and/or reassortment with human influenza A viruses may result in aerosol transmissible viruses with pandemic potential. Although the full range of factors that modulate the transmission and replication of influenza A viruses in humans are not yet known, we are beginning to understand some of the molecular changes that may allow H5N1 influenza A viruses to transmit via aerosols or respiratory droplets among mammals. A better understanding of the biological basis and genetic determinants that confer transmissibility to H5N1 influenza A viruses in mammals is important to enhance our pandemic preparedness.

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    • "The highly pathogenic H5N1 influenza A virus, with a mortality rate of up to 60% in humans (, was chosen for this purpose. To date, human-to-human transmissions are limited but the likelihood of H5N1 mutating into a strain that facilitates transfer necessitates efficient pandemic vaccination preparedness strategies and awareness (Webster and Govorkova, 2006; Imai et al., 2013; Kaplan and Webby, 2013). To date, potential plantproduced subunit HA vaccines (Mortimer et al., 2012) as well as HA DNA vaccine candidates (Mortimer et al., 2013) have been created as part of this South African initiative. "
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    ABSTRACT: The spread of influenza A viruses is partially controlled and prevented by vaccination. The matrix protein 2 ectodomain (M2e) is the most conserved sequence in influenza A viruses, and is therefore a good potential target for a vaccine to protect against multiple virus subtypes. We explored the feasibility of an M2e-based universal influenza A vaccine candidate based on the highly pathogenic avian influenza A virus, H5N1. A synthetic M2e gene was human- and plant-codon optimized and fused in-frame with a sequence encoding the N-terminal proline-rich domain (Zera®) of the γ-zein protein of maize. Zera®M2e was expressed transiently in Nicotiana benthamiana and Sf21 baculovirus/insect cell expression systems, and Zera®M2e protein bodies (PBs) were successfully produced in both expression systems. The plant-produced Zera®M2e PBs were purified and injected into Balb/c mice. Western blot analysis using insect cell-produced Zera®M2e PBs and multiple tandem M2e sequences (5xM2e) fused with the avian influenza H5N1 transmembrane and cytosolic tail (5xM2e_tHA) confirmed the presence of M2e-specific antibodies in immunized mice sera. The immunogenicity of the Zera®M2e indicates that our plant-produced protein has potential as an inexpensive universal influenza A vaccine.
    Full-text · Article · Dec 2015 · Frontiers in Bioengineering and Biotechnology
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    • "In most cases, the individuals affected had been in close contact with infected poultry [1]. Concern exists that the virus could mutate to become more easily transmissible between humans, raising the possibility of an avian influenza pandemic for which the world is not adequately prepared [2]. Influenza A/H5N1 virus is one of the potential avian " pandemic " subtypes to which the majority of the human population has no preexisting antibodies and lacks immune memory [3]. "
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    ABSTRACT: Background: This study describes a double-blinded randomized placebo-controlled phase I clinical trial of A/H5N2 live attenuated influenza vaccine in healthy volunteers. Methods: Two doses of vaccine or placebo were administered intranasally to 30 and 10 subjects, respectively. Nasal swabs were examined for vaccine shedding and local antibody responses; serum samples were tested for binding, hemagglutinating and neutralizing antibodies and peripheral blood mononuclear cells were tested for cell-mediated immune responses. Results: The vaccine was well tolerated and not associated with increased rates of adverse events or the occurrence of serious adverse events. Influenza virus was detected in nasal swabs on the first day in the majority of volunteers (93%), while 17% of volunteers tested positive on the second, none on the third day or later following the first vaccination; lower frequency of shedding was observed after the second vaccination. The vaccine was immunogenic as assessed four weeks after the second dose, with 37.9% and 48.3% of subjects seroconverting by hemagglutination inhibition and neutralization assays, respectively. An immune response was observed in 96.6% subjects that received A/H5N2 LAIV in at least one of the assays conducted. None of the placebo recipients exhibited a response in any of the assays. Conclusion: The A/H5N2 vaccine was safe, well tolerated, and immunogenic in healthy adults. Trial registration: NCT01719783.
    Full-text · Article · Aug 2015 · Vaccine
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    • "Substantial risks to animal and public health are posed by HPAI viruses, as demonstrated by several major epizootics around the world over the last 25 years. This includes the ongoing impact and threat presented by the Eurasian lineage of H5N1 HPAI viruses (referred to here as H5N1) with concerns of zoonotic transmission and the virus then adapting enabling sustained human-to-human transmission with pandemic potential (Imai et al. 2013). Globalization and trade have increased the risk of spread of H5N1 around the world. "
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    ABSTRACT: AimsTo estimate qualitatively the probabilities of release (or entry) of Eurasian lineage H5N1 highly pathogenic avian influenza (HPAI) virus into Great Britain (GB), the Netherlands and Italy through selected higher risk species of migratory water bird. Methods and ResultsThe probabilities of one or more release events of H5N1 HPAI per year (prelease) were estimated qualitatively for 15 avian species, including swans, geese, ducks and gulls, by assessing the prevalence of H5N1 HPAI in different regions of the world (weighted to 2009) and estimates of the total numbers of birds migrating from each of those regions. The release assessment accommodated the migration times for each species in relation to the probabilities of their surviving infection and shedding virus on arrival. Although the predicted probabilities of release of H5N1 per individual bird per year were low, very low or negligible, prelease was high for a few species reflecting the high numbers of birds migrating from some regions. Values of prelease were generally higher for the Netherlands than for GB, while ducks and gulls from Africa presented higher probabilities to Italy compared to the Netherlands and GB. Conclusions Bird species with high values of prelease in GB, the Netherlands and Italy generally originate from within Europe based on data for global prevalence of H5N1 between 2003 and 2009 weighted to 2009. Potential long distance transfer of H5N1 HPAI from North Asia and Eurasia to GB, the Netherlands and Italy is limited to a few species and does not occur from South East Asia, an area where H5N1 is endemic. Significance and Impact of the StudyThe approach accommodates bio-geographic conditions and variability in the estimated worldwide prevalence of the virus. The outputs of this release assessment can be used to inform surveillance activities through focusing on certain species and migratory pathways.This article is protected by copyright. All rights reserved.
    Full-text · Article · Mar 2014 · Journal of Applied Microbiology
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