RESUMO
Background: Despite the success in decreasing varicella-related disease burden, live-attenuated Oka vaccine strain of varicella-zoster virus (vOka) remains neuro-virulence and may establish latency and reactivate, raising safety concerns. Here we aimed to evaluate the safety and immunogenicity of a skin- and neuro-attenuated varicella vaccine candidate (v7D). Methods: This is a randomized, double-blind, placebo-controlled, dose-escalation and age de-escalation phase 1 clinical trial conducted in Liuzhou, China (ChiCTR1900022284). Eligible healthy participants aged 1-49 years, with no history of varicella vaccination and had no history of varicella or herpes zoster were sequentially enrolled and allocated to subcutaneously receive one of the three doses (3.3, 3.9, and 4.2 lg PFU) of v7D, vOka or placebo in a dose-escalation and age de-escalation manner. The primary outcome was safety, assessed by adverse events/reactions within 42 days after vaccination and serious adverse events (SAEs) throughout six months after vaccination. The secondary outcome was immunogenicity, assessed by the VZV IgG antibodies measured with fluorescent antibody to membrane antigen (FAMA) assay. Findings: Between April 2019 and March 2020, totally 224 participants were enrolled. Within 42 days post-vaccination, the incidences of adverse reactions were 37.5%-38.7% in the three doses of v7D groups which were similar to that of the vOka (37.5%) and placebo (34.4%) groups. No SAE has been judged as causally related to vaccination. At 42 days post-vaccination, 100% of children aged 1-12 years in the per-protocol set of immunogenicity cohort of the v7D groups became seropositive. Meanwhile, in the intent-to-treat set of immunogenicity cohort of subjects aged 1-49 years, the geometric mean increases of the three groups of v7D vaccine were 3.8, 5.8 and 3.2, respectively, which were similar to that of the vOka vaccine group (4.4) and significantly higher than that of the placebo group (1.3). Interpretation: The candidate v7D vaccine has been preliminarily shown to be well-tolerated and immunogenic in humans. The data warrant further evaluation of the safety advantage and efficacy of v7D as a varicella vaccine. Funding: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, and Beijing Wantai CO., LTD.
RESUMO
Our study aimed to explore the correlation between age at smoking initiation and smoking cessation for the risk for stroke in China. We investigated 50,174 participants from one of the urban areas of China Kadoorie Biobank (CKB) Study. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for association between smoking and incidence of stroke were estimated using Cox regression model. During a median of 10.7 years of follow-up, 4370 total stroke cases were documented. Among men, comparing current smokers to never smokers, the HR of total stroke for current smokers was 1.279 (95% CI, 1.134-1.443) for total stroke. The HRs of total stroke were 1.344 (1.151-1.570) for those started smoking at age less than 20 years, 1.254 (1.090-1.443) for those started smoking at age 20-30 years, and 1.205 (1.012-1.435) for those started smoking at age 30 year and above, with a dose-response relation (P for trend, 0.004). Comparing former smokers to current smokers, in the low pack-year group, those stopped smoking at age less than 65 years had a 18.2% decreased risk for total stroke (0.818; 0.673-0.994). The decreased risk was not found in those stopped smoking at age 65 years and above. Similar results were observed in the high pack-year group. In conclusion, we found that current smokers had a higher stroke risk than never smokers, and the risk increased with a younger age at smoking initiation. Smoking cessation can reduce the risk for stroke, especially could benefit from cessation at a younger age.
