Safety and immunogenicity of a skin- and neuro-attenuated live vaccine for varicella: a randomized, double-blind, controlled, dose-escalation and age de-escalation phase 1 clinical trial.

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.

Safety and immunogenicity of an Escherichia coli-produced bivalent human papillomavirus type 6/11 vaccine: A dose-escalation, randomized, double-blind, placebo-controlled phase 1 trial.

A dose-escalation, randomized, double-blind, placebo-controlled phase 1 clinical trial enrolled 145 eligible participants aged 18-55 years in March 2015 in Liuzhou, China. Stratified by age and sex, the participants were randomly assigned to receive either 30, 60, or 90 µg of the HPV-6/11 vaccine (n = 41/40/40) or the parallel placebo vaccine (n = 8/8/8) with a 0/1/6-month dose-escalation schedule. Participants were actively followed-up to record local and systemic AEs occurring within 30 days after each vaccination, and SAEs occurred in 7 months. Blood and urine samples of each participant were collected before and 2 days after the first and third vaccination to determine changes in routine blood, serum biochemical, and urine indexes. Serum HPV-6/11-specific IgG and neutralizing antibody levels at month 7 were analyzed. A total of 79 adverse events were reported, and no SAEs occurred. The incidences of total adverse reactions in the 30 µg, 60 µg, and 90 µg HPV vaccine groups and the control group were 31.7%, 50.0%, 42.5%, and 62.5%, respectively. All but one of the adverse reactions was mild or moderate with grade 1 or 2. No vaccine-related changes with clinical significance were found in paired blood and urine indexes before and after vaccinations. All the participants in the per-protocol set seroconverted at month 7 for both IgG and neutralizing antibodies. The candidate novel Escherichia-coli-produced bivalent HPV-6/11 vaccine has been preliminarily proven to be well tolerated and with robust immunogenicity in a phase 1 clinical study, supporting further trials with larger sample size. The study has been registered at ClinicalTrials.gov (NCT02405520).

Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial.

BACKGROUND: The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. METHODS: A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. RESULTS: In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. CONCLUSIONS: The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18-associated high-grade genital lesions and persistent infection in women.

Mental Health of Chinese Peacekeepers in Liberia

Background and Objectives: As part of UN peacekeeping operations in Liberia, China has sent a dozen of batches of peacekeeping force to Liberia for medical, engineering and transporting purposes from 2003 to 2012. This study aimed to explore the mental health of Chinese peacekeepers under the influence of stressful and traumatic events in Liberia. Methods: A total of 440 Chinese peacekeepers were selected by cluster sampling and surveyed by Chinese Military Mental Health Scale (CMMHS) before, during and after peacekeeping deployment. Results: The total CMMHS score (48.90 ± 21.15), depression factor (7.25 ± 3.43), interpersonal sensitivity (4.20 ± 2.15) of Chinese peacekeepers were significantly higher than the Chinese military norm (23.04 ± 14.70, 2.47 ± 2.46, 3.95 ± 2.97 respectively) (p<0.01). The total score and anxiety, somatization factor score of the transporting group were significantly higher than those of the medical group (P <0.05); All CMMHS factors in the transporting group and the medical group were higher than those of the engineering group (p<0.01). CMMHS factors score of the peacekeepers positively correlated with the age, military service duration, years of eudcation and military rank (r = 0.107 ~ 0.523, p<0.05); stepwise linear regression analysis revealed that years of eudcation was the main influence factor for peacekeepers' mental health (t = 2.288 ~ 4.358, p<0.05 ~ 0.01). Conclusions: The mental health status of Chinese peacekeepers was worse than average Chinese servicemen. Peacekeepers of different mission groups had different degree of mental damage, and the years of education was the main influence factor for peacekeepers' mental health, whereas age, military service duration as well as military rank were the secondary influence factors (AU)

No disponible