Sublingual Immunization with a Live Attenuated Influenza A Virus Lacking the Nonstructural Protein 1 Induces Broad Protective Immunity in Mice

The nonstructural protein 1 (NS1) of influenza A virus (IAV) enables the virus to disarm the host cell type 1 IFN defense system. Mutation or deletion of the NS1 gene leads to attenuation of the virus and enhances host antiviral response making such live-attenuated influenza viruses attractive vaccine candidates. Sublingual (SL) immunization with live influenza virus has been found to be safe and effective for inducing protective immune responses in mucosal and systemic compartments. Here we demonstrate that SL immunization with NS1 deleted IAV (DeltaNS1 H1N1 or DeltaNS1 H5N1) induced protection against challenge with homologous as well as heterosubtypic influenza viruses. Protection was comparable with that induced by intranasal (IN) immunization and was associated with high levels of virus-specific antibodies (Abs). SL immunization with DeltaNS1 virus induced broad Ab responses in mucosal and systemic compartments and stimulated immune cells in mucosa-associated and systemic lymphoid organs. Thus, SL immunization with DeltaNS1 offers a novel potential vaccination strategy for the control of influenza outbreaks including pandemics

Efficacy and Safety of Salmeterol/fluticasone Combination Therapy in Infants and Preschool Children with Asthma Insufficiently Controlled by Inhaled Corticosteroids

Background: Clinical evidences of inhaled salmeterol/fluticasone propionate combination (SFC) therapy are insufficient in early childhood asthma. Objectives: To examine the effects of SFC50, a combination product of salmeterol xinafoate (50 μg/day) and fluticasone propionate (100 μg/day), in infants and preschool children with asthma. Methods: The study was conducted at 31 sites in Japan. 35 patients (6 months to 5 years old) with asthma insufficiently controlled by inhaled corticosteroids (100 μg/day) were initiated to treat with SFC50 twice a day for 12 weeks with pressurized metered dose inhalers. The efficacy of SFC50 was assessed using nighttime sleep disorder score as the primary endpoint and the other efficacy measurements. The safety measurement included the incidences of adverse event (AE). Results: Mean patient age was 3.1 years, and 94.2% had mild-to-moderate persistent asthma (atopic type: 65.7%). Nighttime sleep disorder scores, assessed by a nighttime sleep diary, significantly decreased after treatment with SFC50 throughout the study period (p Conclusions: SFC50 improved nighttime sleep disorder score and other efficacy outcome measures with no safety concerns. The results suggest that SFC50 treatment is useful to control the mild-to-moderate asthma in infant and preschool-aged children

Levels of virus-specific IgG induced in mucosal and systemic compartments upon immunization with DeltaNS1 IAV.

<p>BALB/c mice were immunized with different doses of Delta H1N1 (▴ H1N1) or wt live virus A/PR8/34 (PR8) H1N1 (WT) via the sublingual (SL) or intranasal (IN) route. Four weeks later, titers of H1N1 (A/PR8) virus-specific IgG in sera and secretions were determined by ELISA. The values represent mean + SEM ELISA titers determined on groups of 5 mice.</p

Induction of virus-specific IgG and IgA upon immunization with Delta H5N1.

<p>BALB/c mice were immunized with different doses of Delta H5N1 (▴ H5N1) or wt live virus A/PR8/34 (PR8) H1N1 via the sublingual (SL), nasal (N) or intranasal (IN) route. Four weeks later sera were collected and the levels of H5N1 virus-specific IgG and IgA were determined by Delta H5N1 virus-coated ELISA plates. The values represent the mean + SEM (vertical bars) end point ELISA antibody titers determined on 5 mice per group.</p