A recombinant baculovirus expressing the hemagglutinin gene of the influenza virus, A/PR/8/34 (H1N1), under the control of the chicken β-actin promoter, was constructed. To determine the induction of protective immunity in vivo, mice were inoculated with the recombinant baculovirus by intramuscular, intradermal, i.p., and intranasal routes and then were challenged with a lethal dose of the influenza virus. Intramuscular or i.p. immunization with the recombinant baculovirus elicited higher titers of antihemagglutinin Ab than intradermal or intranasal administration. However, protection from a lethal challenge of the influenza virus was only achieved by intranasal immunization of the recombinant baculovirus. Surprisingly, sufficient protection from the lethal influenza challenge was also observed in mice inoculated intranasally with a wild-type baculovirus, as evaluated by reductions in the virus titer, inflammatory cytokine production, and pulmonary consolidations. These results indicate that intranasal inoculation with a wild-type baculovirus induces a strong innate immune response, which protects mice from a lethal challenge of influenza virus.

DNA enzymes are RNA-cleaving single-stranded DNA molecules. We designed DNA enzymes targeting the PB2 mRNA translation initiation (AUG) region of the in£uenza A virus (A/PR/8/34). The modi¢ed DNA enzymes have one or two N3P P-P5P P phosphoramidate bonds at both the 3P P-and 5P Ptermini of the oligonucleotides, which signi¢cantly enhanced their nuclease resistance. These modi¢ed DNA enzymes had the same cleavage activity as the unmodi¢ed DNA enzymes, determined by kinetic analyses, and reduced in£uenza A virus replication by more than 99%, determined by plaque formation. These DNA enzymes are highly speci¢c; their protective e¡ect was not observed in in£uenza B virus (B/Ibaraki)-infected Madin^Darby canine kidney cells.

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Immunological abnormality of T lymphocytes in patients with adult T cell leukemia (ATL) is characterized by abnormal expression of the 55 kD chain of the receptor for interleukin 2 (IL-2R/p55) (Tac), and the down-regulation of CD3 expression. Using serum and culture supernatants of leukaemic cells from ATL patients (Group A) whose CD3 expression was down-regulated and those (Group B) whose CD3 was not low, the possible mechanism of CD3 down-regulation on ATL cells was discussed. When PBMC from normal individuals were cultured with sera from ATL patients for 24 h, CD3 expression revealed by mean fluorescent intensity (MFI) was down-regulated by sera from ATL patients in Group A (MFI: Pt 1 = 51.6 +/- 4.5, Pt 2 = 48.0 +/- 6.9, control = 96.5 +/- 6.6), not by sera from patients in Group B (MFI: Pt 3 = 105.5 +/- 7.9, Pt 4 = 102.5 +/- 8.3, control = 96.5 +/- 6.6). When normal PBMC were cultured with supernatants of leukaemic cells from ATL patients in Group A, this CD3 down-regulating activity was also detected (MFI: Pt 1 = 78.0 +/- 10.2, Pt 2 = 70.6 +/- 8.7, control = 94.0 +/- 6.6). By using gel-chromatography, the fractionated supernatants from ATL patients in Group A decreased CD3 expression of normal PBMC significantly (MFI: Pt = 22.9 +/- 5.8, Pt 2 = 28.8 +/- 7.4, control = 92.1 +/- 9.6). This CD3 down-regulating activity in fractionated supernatant was not inhibited by any lymphokine antibodies, anti-IL-1 alpha antibody (Ab), anti-IL-1B Ab, anti-IL-2 Ab, anti-IL-3 Ab, anti-IL-4 Ab, anti-IL-6 Ab, anti-TNF-alpha Ab and anti-IFN-gamma Ab. Any known cytokines (IL-1, IL-2, IL-3, IL-4, IL-6, TNF-alpha and IFN-gamma) could not modulate CD3 expression of normal PBMC. These findings suggested that there are novel factor(s) with CD3 down-regulating activity in the serum and culture supernatant of ATL patient and those factor(s) are involved in progression of ATL.

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