No abstract

To obtain more insight into IgM in anti-SARS-CoV-2 immunity a prospective cohort study was carried out in 32 volunteers to longitudinally profile the kinetics of the anti-SARS-CoV-2 IgM response induced by administration of a three-dose inactivated SARS-CoV-2 vaccine regimen at 19 serial time points over 456 days. The first and second doses were considered primary immunization, while the third dose was considered secondary immunization. IgM antibodies showed a low secondary response that was different from the other three antibodies (neutralizing, total, and IgG antibodies). There were 31.25% (10/32) (95% CI, 14.30–48.20%) of participants who never achieved a positive IgM antibody conversion over 456 days after vaccination. The seropositivity rate of IgM antibodies was 68.75% (22/32) (95% CI, 51.80–85.70%) after primary immunization. Unexpectedly, after secondary immunization the seropositivity response rate was only 9.38% (3/32) (95% CI, 1.30–20.10%), which was much lower than that after primary immunization (p = 0.000). Spearman’s correlation analysis indicated a poor correlation of IgM antibodies with the other three antibodies. IgM response in vaccinees was completely different from the response patterns of neutralizing, total, and IgG antibodies following both the primary immunization and the secondary immunization and was suppressed by pre-existing immunity induced by primary immunization.

The migratory ability of microglia facilitates their rapid transport to a site of injury to kill and remove pathogens. However, the effect of Treponema pallidum membrane proteins on microglia migration remains unclear. The effect of Tp47 on the migration ability and autophagy and related mechanisms were investigated using the human microglial clone 3 cell line. Tp47 inhibited microglia migration, the expression of autophagy‐associated protein P62 decreased, the expression of Beclin‐1 and LC3‐II/LC3‐I increased, and the autophagic flux increased in this process. Furthermore, autophagy was significantly inhibited, and microglial cell migration was significantly increased after neutralisation with an anti‐Tp47 antibody. In addition, Tp47 significantly inhibited the expression of p‐PI3K, p‐AKT, and p‐mTOR proteins, and the sequential activation of steps in the PI3K/AKT/mTOR pathways effectively prevented Tp47‐induced autophagy. Moreover, Tp47 significantly inhibited the expression of p‐FOXO1 protein and promoted FOXO1 nuclear translocation. Inhibition of FOXO1 effectively suppressed Tp47‐induced activation of autophagy and inhibition of migration. Treponema pallidum membrane protein Tp47‐induced autophagy and inhibited cell migration in HMC3 Cells via the PI3K/AKT/FOXO1 pathway. These data will contribute to understanding the mechanism by which T. pallidum escapes immune killing and clearance after invasion into the central nervous system.

Given the prevalence of low-pathogenic but highly infectious Omicron variants, a cohort study was conducted to assess the response and duration of novel coronavirusinactivated vaccine-induced antibodies 1 year after the third dose (Day 641). Blood samples were collected and anti-spike neutralizing antibodies (neutralizing antibody), total antibodies against the receptor-binding domain of the spike protein (total antibody), and immunoglobulin G antibodies against the spike protein (IgG antibody) were determined. Antibody kinetics and attenuation were evaluated. The results showed that the levels of neutralizing, total, and IgG antibodies on Day 641 were 98.05 IU/mL, 152.8 AU/mL, and 7.68 S/CO, respectively. Levels of anti-SARS-CoV-2 antibodies were higher in the younger subgroup than in the older subgroup at several time points after the second and third doses. The seropositive rate of neutralizing antibodies providing protection from infection or severe infection was 46.87% and 87.5%, and the seropositive rates of total antibody and IgG antibody were maintained at 100% and 90.63%, respectively. The half-lives of neutralizing, total, and IgG antibodies were 186.89, 363.04, and 417.50 days, respectively. Collectively, anti-SARS-CoV-2 antibodies may provide a certain degree of protection from infection 1 year after the third dose and high protection from severe infection.

To identify false-positive SARS-CoV-2 test results caused by novel coronavirus inactivated vaccine contamination, a novel RT-qPCR targeting the ORF1ab and N genes of SARS-CoV-2 and Vero gene was developed. The amplification efficiency, precision, and lower limit of detection (LLOD) of the RT-qPCR assay were determined. A total of 346 clinical samples and 132 environmental samples were assessed, and the diagnostic performance was evaluated. The results showed that the amplification efficiency of the ORF1ab, N, and Vero genes was 95%, 97%, and 93%, respectively. The coefficients of variation of Ct values at a concentration of 3 × 104 copies/mL were lower than 5%. The LLOD for the ORF1ab, N, and Vero genes reached 8.0, 3.3, and 8.2 copies/reaction, respectively. For the 346 clinical samples, our RT-qPCR assay identified SARS-CoV-2-positive and SARS-CoV-2-negative samples with a sensitivity of 100.00% and a specificity of 99.30% and novel coronavirus inactivated vaccine-contaminated samples with a sensitivity of 100% and a specificity of 100%. For the environmental samples, our RT-qPCR assay identified novel coronavirus inactivated vaccine-contaminated samples with a sensitivity of 88.06% and a specificity of 95.38%. In conclusion, the RT-qPCR assay we established can be used to diagnose COVID-19 and, to a certain extent, false-positive results due to vaccine contamination.