Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China.

BACKGROUND: Enterovirus 71 (EV71) is one of the major causative agents of outbreaks of hand, foot, and mouth disease or herpangina worldwide. This phase 3 trial was designed to evaluate the efficacy, safety, and immunogenicity of an EV71 vaccine. METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter trial in which 10,007 healthy infants and young children (6 to 35 months of age) were randomly assigned in a 1:1 ratio to receive two intramuscular doses of either EV71 vaccine or placebo, 28 days apart. The surveillance period was 12 months. The primary end point was the occurrence of EV71-associated hand, foot, and mouth disease or herpangina. RESULTS: During the 12-month surveillance period, EV71-associated disease was identified in 0.3% of vaccine recipients (13 of 5041 children) and 2.1% of placebo recipients (106 of 5028 children) in the intention-to-treat cohort. The vaccine efficacy against EV71-associated hand, foot, and mouth disease or herpangina was 94.8% (95% confidence interval [CI], 87.2 to 97.9; P<0.001) in this cohort. Vaccine efficacies against EV71-associated hospitalization (0 cases vs. 24 cases) and hand, foot, and mouth disease with neurologic complications (0 cases vs. 8 cases) were both 100% (95% CI, 83.7 to 100 and 42.6 to 100, respectively). Serious adverse events occurred in 111 of 5044 children in the vaccine group (2.2%) and 131 of 5033 children in the placebo group (2.6%). In the immunogenicity subgroup (1291 children), an anti-EV71 immune response was elicited by the two-dose vaccine series in 98.8% of participants at day 56. An anti-EV71 neutralizing antibody titer of 1:16 was associated with protection against EV71-associated hand, foot, and mouth disease or herpangina. CONCLUSIONS: The EV71 vaccine provided protection against EV71-associated hand, foot, and mouth disease or herpangina in infants and young children. (Funded by Sinovac Biotech; ClinicalTrials.gov number, NCT01507857.).

Effects of mitochondrial ATP-sensitive potassium channels on the proliferation and secretion of human airway smooth muscle cells.

Bronchial asthma is the common chronic inflammatory disease and is characterized by chronic airway inflammation, airway remodeling, and airway hyperreactivity (AHR). Aim of this study was to investigate the effects of mitochondrial ATP-sensitive potassium channels (MitoKATP) on the proliferation and secretion of human airway smooth muscle cells (HASMCs). HASMCs were treated with the serum from asthmatic patients to establish HASMCs asthma model of passive sensitization. Rhodamine 123 (R-123) and 2,7-dichloro-dihydrofluorescein diacetate (DCFH-DA) fluorescence staining were used to detect mitochondrial membrane potential (Δψm) and the content of reactive oxygen species (ROS) in the cells, respectively. The cell counting was used to detect cell proliferation, and RT-PCR was used to detect the expression of TGF-ß1 mRNA. In the normal + Diazoxide group, the fluorescence intensity of R-123, ROS content, cell proliferation and TGF-ß1 expression were enhanced, compared with the normal control group (p<0.05). There were no significant differences between the normal + 5-hydroxydecanoate (5-HD) group and the normal control group. In the asthma model control group, the fluorescence intensity of R-123, ROS content, cell proliferation and TGF-ß1 expression were enhanced, compared with normal control group, (p<0.05). The aforementioned indices were enhanced in the asthma model + Diazoxide group, when compared with the asthma model control group, whereas these indices were attenuated in the asthma model + 5-HD group, when compared with the asthma model control group (p<0.05). In conclusion, asthma could activate MitoKATP channels in HASMCs, promote HASMC proliferation and TGF-ß1 expression.

[An epidemiological investigation of the rabies between 1999 - 2008 in Yancheng city, Jiangsu province.].

OBJECTIVE: To better understand the epidemiology of rabies during the past ten years in Yancheng city, Jiangsu province. METHODS: Data was collected and analyzed on rabies cases in Yancheng. Density and vaccination rate on Canine, Rate of injured people bit by dogs, and the information of post-exposure prophylaxis were studied. Rabies virus in the dog brains, collected around the epidemic areas of Yancheng, were detected and analyzed. RESULTS: A total of 135 human rabies cases occurred from 1999 through 2008, and formed the second epidemic peak since 1958. Of these victims, 84% (114) were farmers. In general, the rate of people having dogs were 3% - 6% per 100 people, and the injured person-times of 100 dogs were 6.37 per year. Notably, the vaccination rate of dogs was only 20%. Of those people injured by dogs and other animals, 77% had received post-exposure treatment, and only 5% - 10% had been administered anti-rabies serum. Rabies virus antigen was found in 4 (3.6%) of 111 brain specimens among dogs collected from epidemic areas. Genetic analysis of N and G genes, which were amplified from brain specimens, indicated that these viruses belong to genotype I rabies and expressing a close relationship with the Chinese vaccine strain CTN. CONCLUSION: The large number of dogs with low vaccination rate among them, together with the incorrect and low post-exposure treatment in rural areas seemed to be responsible for the outbreak of rabies in Yancheng city.