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.
"In most cases, the individuals affected had been in close contact with infected poultry . 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 . 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 . "
[Show abstract][Hide abstract] 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.
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.
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.
The A/H5N2 vaccine was safe, well tolerated, and immunogenic in healthy adults.
[Show abstract][Hide abstract] ABSTRACT: Two ferret-adapted H5N1 viruses capable of respiratory droplet transmission have been reported with mutations in the hemagglutinin receptor-binding site and stalk domains. Glycan microarray analysis reveals that both viruses exhibit a strong shift towards binding to 'human-type' α2-6 sialosides, but with notable differences in fine specificity. Crystal structure analysis further shows that the stalk mutation causes no obvious perturbation of the receptor-binding pocket, consistent with its impact on hemagglutinin stability without effecting receptor specificity.
Journal of Virology 10/2013; 88(1). DOI:10.1128/JVI.02690-13 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The best approach to control the spread of influenza virus during a pandemic is vaccination. Yet, an appropriate vaccine is not available early in the pandemic since vaccine production is time consuming. For influenza strains with a high pandemic potential like H5N1, stockpiling of vaccines has been considered but is hampered by rapid antigenic drift of the virus. It has, however, been shown that immunization with a given H5N1 strain can prime the immune system for a later booster with a drifted variant. Here, we investigated whether whole inactivated virus (WIV) vaccine can be processed to tablets suitable for sublingual (s.l.) use and whether s.l. vaccine administration can prime the immune system for a later intramuscular (i.m.) boost with a heterologous vaccine. In vitro results demonstrate that freeze-drying and tableting of WIV did not affect the integrity of the viral proteins or the hemagglutinating properties of the viral particles. Immunization experiments revealed that s.l. priming with WIV (prepared from the H5N1 vaccine strain NIBRG-14) 4 weeks prior to i.m. booster immunization with the same virus strongly enhanced hemagglutination-inhibition (HI) titers against NIBRG-14 and the drifted variant NIBRG-23. Moreover, s.l. (and i.m.) immunization with NIBRG-14 also primed for a subsequent heterologous i.m. booster immunization with NIBRG-23 vaccine. In addition to HI serum antibodies, s.l. priming enhanced lung and nose IgA responses, while i.m. priming enhanced lung IgA but not nose IgA levels. Our results identify s.l. vaccination as a user-friendly method to prime for influenza-specific immune responses toward homologous and drifted variants.
The AAPS Journal 01/2014; 16(2). DOI:10.1208/s12248-014-9565-z · 3.80 Impact Factor
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