RESUMEN
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 â ¡, 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, â ¡, 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.
Asunto(s)
Poliomielitis , Poliovirus , Humanos , Preescolar , Vacuna Antipolio de Virus Inactivados , Poliomielitis/prevención & control , Vacuna Antipolio Oral , Anticuerpos Antivirales , Esquemas de Inmunización , Anticuerpos Neutralizantes , Inmunogenicidad VacunalRESUMEN
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.
RESUMEN
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).