Safety and immunogenicity of a modified COVID-19 mRNA vaccine,SYS6006,as a fourth-dose booster following three doses of inactivated vaccines in healthy adults:an open-labeled Phase 1 trial

The continuous emergence of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants led to a rapid decline in protection efficacy and neutralizing titers even after three doses of COVID-19 vaccines.Here,we report an open-labeled Phase I clinical trial of a modified mRNA vaccine(SYS6006)as a fourth-dose booster in healthy adults.Eighteen eligible participants,who had completed three doses of inactivated COVID-19 vaccines,received a fourth boosting dose of SYS6006-20μg.Eighteen convalescent COVID-19 patients were enrolled for the collection of serum samples as a comparator of immunogenicity.The primary endpoint of this trial was titers of anti-receptor binding domain of spike glycoprotein(RBD)antibodies of the Omicron strain(BA.2 and BA.4/5)in serum;titers of neutralizing antibodies against pseudovirus of the Omicron strain(BA.2 and BA.4/5).The secondary endpoint was the incidence of adverse events within 30 days after the boosting.The exploratory endpoint was the cellular immune responses(interferon gamma,IFN-γ).This trial was registered with the Chinese Clinical Trial Registry website.No serious adverse events were reported within 30 days after vaccination.No Grade 3 fever or serious adverse event was reported in the SYS6006 group.Notably,SYS6006 elicited higher titers and longer increases in anti-RBD antibodies and neutralizing antibodies(>90 days)compared with the convalescent group(P<0.0001)against Omicron strain(BA.2 and BA.4/5).Besides,higher positive spots of T-cell-secreting IFN-γwere observed in the SYS6006 group than those in the convalescent group(P<0.05).These data demonstrated that SYS6006 was well tolerated and highly immunogenic,generating a stronger and more durable immune response against different variants of SARS-CoV-2.

Potassium 2-(l-hydroxypentyl)-benzoate attenuates neuroinflammatory responses and upregulates heme oxygenase-1 in systemic lipopolysaccharide-induced inflammation in mice

A neuroinflammatory response is commonly involved in the progression of many neurodegenerative diseases. Potassium 2-(1-hydroxypentyl)-benzoate(PHPB), a novel neuroprotective compound, has shown promising effects in the treatment of ischemic stroke and Alzheimer's disease(AD). In the present study, the anti-inflammatory effects of PHPB were investigated in the plasma and brain of C57BL/6 mice administered a single intraperitoneal(i.p.) injection of lipopolysaccharide(LPS). Levels of i NOS and the cytokines TNFα, IL-1β and IL-10 were elevated in plasma, cerebral cortex and hippocampus after LPS injection and the number of microglia and astrocytes in cortex and hippocampus were increased. LPS also upregulated the expression of heme oxygenase-1(HO-1) in the cortex and hippocampus. PHPB reduced the levels of i NOS and cytokines in the plasma and brain, decreased the number of microglia and astrocytes and further enhanced the upregulation of HO-1. In addition, PHPB inhibited the LPS-induced phosphorylation of ERK, P38 and JNK. These results suggest that PHPB is a potential candidate in the treatment of neurodegenerative diseases through inhibiting neuroinflammation.