Chinese Ministry of Science and Technology, National Natural Science Foundation (China).

No abstract

Hepatitis B was still a worldwide health problem. This study aimed to conducted a systematic review and meta-analysis to assess a more precise estimation of factors that influence the response to hepatitis B vaccine in adults. Our included studies examined seroprotection rates close to the end of vaccination schedules in healthy adult populations. This meta-analysis including 21053 adults in 37 articles showed that a significantly decreased response to hepatitis B vaccine appeared in adults (age ≥ 40) (RR:1.86, 95% CI:1.55–2.23), male adults (RR:1.40, 95% CI:1.22–1.61), BMI ≥ 25 adults (RR:1.56, 95% CI:1.12–2.17), smoker (RR:1.53, 95% CI:1.21–1.93), and adults with concomitant disease (RR:1.39, 95% CI:1.04–1.86). Meanwhile, we further found a decreased response to hepatitis B vaccine appeared in adults (age ≥ 30) (RR:1.77, 95% CI:1.48–2.10), and adults (age ≥ 60) (RR:1.30, 95% CI:1.01–1.68). However, there were no difference in response to hepatitis B vaccine both in alcoholic (RR:0.90, 95% CI:0.64–1.26) and 0-1-12 vs. 0-1-6 vaccination schedule (RR:1.39, 95% CI:0.41–4.67). Pooling of these studies recommended the sooner the better for adult hepatitis B vaccine strategy. More vaccine doses, supplemental/additional strengthening immunity should be emphasized on the susceptible population of increasing aged, male, BMI ≥ 25, smoking and concomitant disease. The conventional 0-1-6 vaccination schedule could be still worth to be recommended.

Summary Recent advances in gene editing technology have introduced the potential for application of mutagenesis approaches in non-human primates to model human development and disease. Here we report successful TALEN-mediated mutagenesis of an X-linked, Rett Syndrome (RTT) gene, the methyl-CpG binding protein 2 (MECP2), in both rhesus and cynomolgus monkeys. Microinjection of MECP2-targeting TALEN plasmids into rhesus and cynomolgus zygotes leads to effective gene editing of MECP2 with no detected off-target mutagenesis. Male rhesus (2) and cynomolgous (1) fetuses carrying MECP2 mutations in various tissues including testes were miscarried during mid-gestation, consistent with RTT-linked male embryonic lethality in humans. One live delivery of a female cynomolgus monkey occurred after 162 days of gestation, with abundant MECP2 mutations in peripheral tissues. We conclude that TALEN-mediated mutagenesis can be an effective tool for genetic modeling of human disease in non-human primates.