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RNA polymerase of influenza virus is a specific enzyme necessary for the viral replication. A siRNA against the RNA polymerase and the RNA polymerase inhibitor L-742,001 reduced accumulation of viral RNAs in the infected cells. L-742,001 strongly inhibited virus re-growth after removal of the agent from the culture, whereas the neuraminidase inhibitor zanamivir did not. L-742,001-resistant mutants...
Immune responses induced by a nasal influenza vaccine with a mutant cholera toxin (CT112K), known to be a safe adjuvant, were characterized in BALB/c mice to confirm the most suitable regimen of this vaccine for humans. Mice received a primary intranasal administration of the adjuvant (0.1μg)-combined PR8 vaccine (0.1μg) and a secondary administration of the PR8 vaccine alone (0.1μg) 4 weeks later...
Effects of intranasal administration of influenza vaccine on persistent viral infection in γ-ray irradiated mice were examined. BALB/c mice were exposed to a sub-lethal dose of γ-ray (7Gy) and infected intranasally with non-lethal A/PR/8/34 (PR8, H1N1) viruses. The mice irradiated on days 0 or +2 of infection showed a significant weight loss with a slight decrease in survival rate 3 weeks after infection...
Protection against a lethal influenza B virus infection was examined in BALB/c mice immunized with plasmid DNAs encoding hemagglutinin (HA), neuraminidase (NA and NB) and nucleoprotein (NP) from the B/Ibaraki/2/85 virus. Each DNA vaccine was administered twice, 3 weeks apart, at a dose of 1 μg per mouse by particle-mediated DNA transfer to the epidermis (gene gun) or at a dose of 30 μg per mouse by...
The effectiveness and safety of mutant Escherichia coli heat-labile enterotoxin, LT H44A (His to Arg substitution at position 44 from the N-terminus of the A1 fragment of the A subunit) as an adjuvant for nasal influenza vaccine were examined. (1) When 0.2 μg of LT H44A, together with 0.2 μg of influenza A/PR/8/34 virus (PR8, H1N1) vaccine, was administered intranasally into BALB/c mice (twice, 4...
Cross-protection against a lethal influenza virus infection was examined in BALB/c mice immunized with plasmid DNAs encoding the neuraminidase (NA) from different subtype A viruses. Each NA-DNA was administered twice, 3 weeks apart, at the dose of 1<space>μg per mouse by particle-mediated DNA transfer to the epidermis (gene gun) or at a dose of 30<space>μg per mouse by electroporation...
Electroporation for the transfer of plasmid DNA encoding influenza virus hemagglutinin (HA) into muscle or nasal mucosa was tried in BALB/c mice to examine the efficacy of this method for inducing anti-HA immune responses and providing protection against homologous A/PR/8/34 (PR8) virus infection. Mice were immunized by two injections, 3 weeks apart, of HA-DNA with electroporation into the muscle...
Inactivated influenza vaccine was administered intranasally to BALB/c mice together with an adjuvant (cholera toxin B subunit [CTB] supplemented with a trace amount of the whole toxin, CTB*) and its ability to induce innate immunity and confer protection against influenza was examined. Nasal wash virus titres 3 days after inoculation of homologous viruses were measured as an index of the ability of...
The effect of sublethal γ-ray irradiation on the protection conferred by a nasal influenza vaccine was investigated in BALB/c mice. A radiation dose of 7 Gy was selected as the sublethal dose as this caused exacerbation of the influenza but was not lethal in the mouse model. Mice were irradiated 7 days before, on the same day as, and 7 days after, administration of a nasal influenza vaccine, and were...
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