Immunogenicity and immune persistence in 4-year-old children completing four doses of Sabin strain or wild strain inactivated poliovirus vaccine: A phase IV, open-labeled, parallel-controlled observational study.

BACKGROUND: Sabin strain inactivated poliovirus vaccine (hereinafter as "sIPV") has been marketed globally in recent years, and more data on its immune persistence are needed. METHODS: This is a phase IV, open-labeled, parallel-controlled observational study based on phase III clinical trial as required by the China National Medical Products Administration (NMPA). At least 450 subjects aged four years (48-54 months) who received four doses at 2, 3, 4 and 18 months of age of sIPV or wild strain poliovirus vaccine (wIPV) in phase III clinical trial enrolled at a 2:1 ratio and collected blood samples for neutralizing antibody testing. RESULTS: A total of 500 subjects of four years old (334 in the sIPV group and 166 in wIPV group) were finally enrolled. The seropositivity rates (≥1:8) of neutralizing antibodies against serotype I-III were all 100.00% in all participants, and the geometric mean titers (GMT) were 1117.33 vs. 337.77 against serotype I, 632.72 vs. 267.34 against serotype Ⅱ, 1665.98 vs. 923.02 against serotype III in the sIPV group and wIPV group respectively at 4 years old. The seropositivity rates and GMTs of neutralizing antibodies in the test group were non-inferior to that of the control group against all three serotypes at different time points (P < 0.0001). The antibody GMT experienced a 10-fold, 8-fold, and 7-fold decline for serotypes I, Ⅱ, and III in the sIPV group, and a 13-fold, 7-fold, and 7-fold decline in the wIPV group from one month after booster vaccination to 4 years old. CONCLUSIONS: The neutralizing antibody level is much higher than the seroprotection cutoff (≥1:8) among children of 4 years old who completed the four-dose vaccination of either sIPV or wIPV. Therefore, another booster vaccination is not recommended at 4 years old. Longer immune persistence observation is still ongoing. REGISTRATION: ClinicalTrials.gov Identifier: NCT04989231.

Batch-to-batch consistency trial of an adenovirus type-5 vector-based COVID-19 vaccine in adults aged 18 years and above.

BACKGROUND: The demonstration of batch-to-batch consistency is indispensable for quality control of vaccines. METHODS: We conducted a randomized, double-blind, parallel-controlled trial to evaluate the immunogenicity consistency of a single shot of Ad5-nCoV in healthy adults who had not previously received any COVID-19 vaccine. All eligible participants were randomly assigned equally to receive one of the three consecutive batches of Ad5-nCoV (5 × 1010 viral particles/vial, 0.5 mL). The primary endpoint was geometric mean titers (GMTs) of serum SARS-CoV-2 receptor-binding domain (RBD)-specific IgG on day 28 post-vaccination. RESULTS: One thousand fifty participants were enrolled, with 350 (33%) participants per group. On day 28 post-vaccination, GMTs in three groups were 78.3 binding antibody units (BAU)/mL (95% CI 70.3-87.3), 82.9 BAU/mL (73.9-92.9), and 78.8 BAU/mL (70.2-88.4), respectively. The two-sided 95% CIs for the GMT ratios between each pair of batches were all between 0.67 and 1.5. The highest incidence of solicited adverse reactions within 7 days post-vaccination was reported by batch 3 recipients (23.1% versus 15.1% in batch 1 recipients and 14.6% in bath 2 recipients; p = 0.0039). None of the serious adverse events were related to vaccination. CONCLUSIONS: Immunogenicity consistency between consecutive batches of Ad5-nCoV was well established in adults. CLINICAL TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT05313646).

Downregulation of interleukin-1 beta via Jmjd3 inhibition improves post-myocardial infarction depression.

Background: Patients with myocardial infarction (MI) comorbid with the depressive disorder may have increased serum cytokine concentrations, notably, of interleukin-1 beta (IL-1ß). The histone H3 lysine-27 (H3K27) demethylase Jmjd3 is crucial in cytokine regulation, and administering an H3K27 demethylase-selective inhibitor (GSK J4) might ameliorate inflammatory symptoms. We hypothesized that Jmjd3 might regulate IL-1ß concentrations, thus affecting the development of post-MI depression (PMD). In this study, a mouse model was created to examine the connection between IL-1ß and PMD and determine the regulatory function of cytokine in controlling inflammation and depressive symptoms. Methods: MI was induced in 30 5-week-old male C57BL/6N mice via a left coronary ligation, and MI onset was confirmed by electrocardiogram (ECG). After treatment with dimethylsulfoxide (DMSO) or GSK J4 for 14 days, the mice were subjected to tail-suspension tests (TSTs) and forced swimming tests (FSTs) before being sacrificed for tissue harvest. Results: In the TSTs, the GSK J4-treated MI mice displayed a significantly shorter immobility time than did the DMSO-treated MI mice (P<0.001). In the FSTs, the DMSO-treated MI mice showed a significantly longer immobility time than did the DMSO-treated sham-operated mice (P<0.001). The GSK J4-treated MI mice had a significantly reduced immobility time compared to the DMSO-treated MI mice (P<0.001). IL-1ß expression in the myocardium, hippocampus, prefrontal cortex (PFC), and hypothalamus increased after MI onset (P=0.003, 0.015, 0.0003, and 0.013, respectively) but decreased after treatment with GSK J4 (P<0.001, P=0.005, P<0.001, P=0.018, respectively). In the myocardium and hypothalamus, Jmjd3 expression levels were lower in mice that received GSK J4 treatment than in those that received DMSO treatment (P<0.05). Conclusions: GSK J4 inhibited the cardiac expression of IL-1ß and Jmjd3, and alleviated PMD in MI mice. Therefore, IL-1ß and Jmjd3 may be critical in the pathogenesis of PMD, and Jmjd3 may potentially serve as a target for PMD treatment.