Immunogenicity and safety of a recombinant COVID-19 vaccine (ZF2001) as heterologous booster after priming with inactivated vaccine in healthy children and adolescents aged 3-17 years: an open-labeled, single-arm clinical trial.

Considering that neutralizing antibody levels induced by two doses of the inactivated vaccine decreased over time and had fallen to low levels by 6 months, and homologous and heterologous booster immunization programs have been implemented in adults in China. The booster immunization of recombinant COVID-19 vaccine (ZF2001) after priming with inactivated vaccine in healthy children and adolescents has not been reported. We performed an open-labeled, single-arm clinical trial to evaluate the safety and immunogenicity of heterologous booster immunization with ZF2001 after priming with inactivated vaccine among 240 population aged 3-17 years in China. The primary outcome was immunogenicity, including geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates of SARS-CoV-2 neutralizing antibodies against prototype SARS-CoV-2 and Omicron BA.2 variant at 14 days after vaccination booster. On day 14 post-booster, a third dose booster of the ZF2001 provided a substantial increase in antibody responses in minors, and the overall occurrence rate of adverse reactions after heterologous vaccination was low and all adverse reactions were mild or moderate. The results showed that the ZF2001 heterologous booster had high immunogenicity and good safety profile in children and adolescents, and can elicit a certain level of neutralizing antibodies against Omicron.Trial registration NCT05895110 (Retrospectively registered, First posted in ClinicalTrials.gov date: 08/06/2023).

Molecular control of arsenite-induced apoptosis in Caenorhabditis elegans: roles of insulin-like growth factor-1 signaling pathway.

Apoptosis is one of the main cellular processes in responses to arsenic, the well known environmental carcinogen. By using the nematode Caenorhabditis elegans as an in vivo model, we found that insulin-like growth factor-1 networks and their target protein DAF-16/FOXO, known as key regulators of energy metabolism and growth, played important roles in arsenite-induced apoptosis. Inactivation of DAF-2, AGE-1 and AKT-1 caused worms more susceptible to arsenite-induced apoptosis, which could be attenuated by DAF-16 knockout. Worms with inactivated AKT-2 and SGK-1 or with constitutively activated PDK-1 and AKT-1 showed low levels of apoptosis, which could be elevated by DAF-16 mutation. Our results demonstrated that DAF-2/IGF-1R, AGE-1/PI3K, PDK-1/PDK1 and AKT-1/PKB negatively regulated the arsenite-induced apoptosis, whereas AKT-2 and SGK-1 acted proapoptotically. DAF-16/FOXO antagonized IGF-1 signals in signaling the arsenite-induced apoptosis, and apoptosis promoted by DAF-16 inactivation was attributed to its higher sensitivity to oxidative stress.