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•This is the first report of the co-administration of CoronaVac with IIV4 in adults aged 18–59 years.•The occurrence of adverse reactions (AR) in all groups was no more than 20% and 98.9% of the ARs were mild or moderate.•Both concomitant or separate administration of CoronaVac and IIV4 could induce sufficient immunogenicity.•A slight interference with the immune response to CoronaVac was observed in participants in C2 subgroup.•At least two doses of CoronaVac are needed to fulfill the primary immunization of inactivated COVID-19 vaccine. Studies are needed for evidence of inactivated COVID-19 vaccine co-administered with influenza vaccine. A randomized, open-label, controlled study was conducted in Zhejiang Province, China. Eligible healthy adults aged 18–59 years underwent randomization at a ratio of 1:1:2 to receive inactivated quadrivalent influenza vaccine (IIV4) either concomitantly with the first (C1 subgroup) or the second (C2 subgroup) dose of CoronaVac, or 14 days after the first dose of CoronaVac (S group). The primary purpose of the study was to prove the non-inferiority in seroconversion rate of antibody against SARS-CoV-2. Overall, 480 participants were enrolled, with 120, 120, and 240 randomly assigned to the C1, C2, and S groups, respectively. As lower bound of the two-sided 95% confidence interval (CI) of the difference for the seroconversion rate of antibodies against SARS-CoV-2 was over −10%, the immune response for CoronaVac in the C group (93.1% [89.0, 96.0]) was non-inferior to that in the S group (95.2% [91.5, 97.6]) in the per-protocol set. A lower GMT of antibody against SARS-CoV-2 was observed in the C group as compared to the S group (27.5 vs. 38.1, P = 0.0001). Decrease of immune response to CoronaVac was mainly observed in participants received IIV4 concomitantly with their second dose of CoronaVac (C2 subgroup), with a seroconversion rate of 89.7% (95CI: 82.6%-94.5%) and a GMT of 23.3. The occurrences of vaccine related adverse reactions were no more than 20% and comparable among different groups. Most of the adverse reactions were mild and moderate. Co-administration of inactivated COVID-19 vaccine and seasonal influenza vaccine, especially the administration regimen that the seasonal influenza vaccine co-administered with the first dose of the inactivated COVID-19 vaccine, would be feasible.

Concomitant administration of COVID-19, influenza, and pneumococcal vaccines could reduce the burden on healthcare systems. However, the immunogenicity and safety of various combinations of a third booster dose of SARS-CoV-2 inactivated vaccine (CoronaVac), inactivated quadrivalent influenza vaccine (IIV4), and 23-valent pneumococcal polysaccharide vaccine (PPV23), particularly in different age groups, is still unknown. A phase 4, randomized, open-label, controlled trial was conducted in Beijing, China. 636 healthy adults were divided into two age groups (18-59 and ≥60 years) and randomized equally into three groups: CoronaVac and IIV4 followed by PPV23; CoronaVac and PPV23 followed by IIV4; or CoronaVac followed by IIV4 and PPV23, with a 28-day interval between vaccinations. Immunogenicity was evaluated by measuring antibody titers, and safety was monitored. ClinicalTrials.gov Identifier: NCT05298800. Co-administration of a third dose of CoronaVac, IIV4, and PPV23 in any combination was safe. Among adults aged 18-59, co-administration with PPV23 maintained non-inferiority of antibody levels for CoronaVac and IIV4, despite a slight reduction in antibody responses. This reduction was not observed in participants ≥60 years. Furthermore, co-administration of IIV4 and PPV23 affected seroconversion rates for both vaccines. Co-administration of the third dose of SARS-CoV-2 inactivated vaccine with the influenza vaccine, followed by PPV23, may be optimal for adults aged 18-59. In adults ≥60, all vaccine combinations were immunogenic, suggesting a flexible vaccination approach. Since antibody measurements were taken 28 days post-vaccination, ongoing surveillance is essential to assess the longevity of the immune responses.

AbstractBackgroundConcomitant administration refers to the receipt of two or more vaccines during a single healthcare encounter, which is an efficient way to increase vaccination coverage in children. However, the post-marketing safety studies of concomitant administration are scarce. Inactivated hepatitis A vaccine (Healive®) has been used widely in China and other countries for more than a decade. We aimed to explore the safety of Healive® co-administered with other vaccines compared to Healive® alone in children under 16 years old. MethodsWe retrieved Adverse Events Following Immunization (AEFI) cases and vaccination doses of Healive® during 2020–2021 in Shanghai, China. The AEFI cases were divided into concomitant administration group and Healive® alone group. We used administrative data on vaccine doses as denominators to calculate and compare crude reporting rates between groups. We also compared baseline gender and age distribution, clinical diagnoses, and time interval from vaccination to onset of symptoms between groups. ResultsA total 319,247 doses of inactivated hepatitis A vaccine (Healive®) were used and 1,020 AEFI cases (319.50 per million doses) associated with Healive® were reported during 2020–2021 in Shanghai. There were 259,346 doses concomitantly administered with other vaccines and 830 AEFI cases (320.04 per million doses) were reported. There were 59,901 doses of Healive® that vaccinated alone, with 190 AEFI cases (317.19 per million doses). There was only one case with serious AEFI in concomitant administration group, with a rate of 0.39 per million doses. Reported rates of AEFI cases were similar between groups in general (p > 0.05). ConclusionConcomitant administration of inactivated hepatitis A vaccine (Healive®) with other vaccines has a similar safe profile as Healive® alone.

There is no clear conclusion on the immunogenicity and adverse events of concomitant administration the viral respiratory infectious disease vaccines. We aimed to evaluate the impact of concomitant administering viral respiratory infectious disease vaccines on efficiencies, safety and influencing factors. This meta-analysis included studies from PubMed, Embase, Cochrane Central Register of Clinical Trials, Web of Science, WHO COVID-19 Research, and ClinicalTrials.gov databases. Randomized controlled trials of the adult participants concomitant administered with viral respiratory infectious disease vaccine and other vaccines were included. The main outcomes were the seroconversion rate and seroprotection rate of each vaccine. Used the Mantel-Haenszel fixed effects method as the main analysis to estimate the pooled RRs and the corresponding 95% confidence intervals. The risk of bias for each trial was assessed using the Cochrane Handbook for Systematic Reviews of Interventions, while evidence certainty was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. A total of 21 studies comprising 14060 participants with two types of vaccines were retained for the meta-analysis. Concomitant immunization reduced the geometric mean titer (RR: 0.858, 95% CI: (0.785 to 0.939)) and the geometric mean fold rise (0.754 (0.629 to 0.902)) in the SARS-COV-2 vaccine group but increased the seroconversion rate (1.033 (1.0002 to 1.067)) in the seasonal influenza vaccine group. Concomitant administration were influenced by the type of vaccine, adjuvant content, booster immunization, and age and gender of the recipient. This meta-analysis suggested that the short-term protection and safety of concomitant administered were effective. Appropriate adjuvants, health promotion and counselling and booster vaccines could improve the efficiency and safety of Concomitant vaccination. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022343709.

Background Nanoliposomal irinotecan (nal‐IRI) plus 5‐fluorouracil (5‐FU)/levo‐leucovorin (Levo‐LV) therapy is recommended as the standard of care for unresectable locally advanced (UR‐LA) and metastatic pancreatic cancer after failure of gemcitabine‐containing regimens. Although the concomitant administration of nal‐IRI and Levo‐LV benefits from a reduced hospital stay, nal‐IRI is usually administered after Levo‐LV owing to insufficient data on compatibility reactions. This study aimed to compare the safety and efficacy of the sequential and concomitant administration of nal‐IRI and Levo‐LV. Methods Data of patients with UR‐LA or metastatic pancreatic cancer who received nal‐IRI plus 5‐FU/Levo‐LV between 2020 and 2023 at Shizuoka Cancer Center were retrospectively collected. Patients were classified into the sequential administration group (Group S) and concomitant administration group (Group C) to compare adverse events, infusion time, and survival. Univariate and multivariate analyses were performed to identify independent prognostic factors in each group. Results A total of 94 patients were included (44 in Group S and 50 in Group C). There was no significant difference in the incidence of Grade 3 or higher adverse events between the two groups. The median total infusion times for nal‐IRI plus 5‐FU/Levo‐LV in Groups S and C were 271 and 149 min, respectively (p < 0.001). Overall survival estimates were 5.6 months (95% confidence interval [CI] 3.78–8.57) in Group S and 8.4 months (95% CI 6.77–10.3) in Group C (unstratified HR 0.65, 95% CI 0.42–1.02; p = 0.058). In the multivariate analysis for PFS and OS, the method of administration was not identified as an independent prognostic factor. Concomitant administration of Levo‐LV with nal‐IRI may not increase adverse events or impact efficacy while reducing infusion time. Conclusion Concomitant administration of Levo‐LV with nal‐IRI may not increase adverse events or impact efficacy compared to sequential administration.

People in Eastern countries hold a tradition of soaking herbal medicine in wine; however, the efficacy and safety of herbal wine have not been rigorously assessed. By assessing the efficacy of resveratrol (RSV) in ethanol against alcoholic liver disease (ALD) in mice, we aimed to offer a perspective on the use of herbal wine. To simulate the behaviour of herbal wine users, RSV (15 mg/kg) soaked in ethanol (RSV-alcohol) was administrated via gavage to the mice, here with alcohol consumption-induced ALD. RSV soaked in water (RSV-water) was the treatment control. The efficacy and safety of RSV on ALD were evaluated. Compared with the RSV-water group, a higher rate of mortality was found in the RSV-alcohol group (50.0% vs. 20.0%), which also exhibited more severe liver injury. RSV significantly increased the exposure of alcohol by 126.0%, which was accompanied by a significant inhibition of the ethanol metabolic pathway. In contrast, alcohol consumption significantly reduced exposure to RSV by 95.0%. Alcohol consumption had little effect on the expression of drug-metabolizing enzymes in RSV; however, alcohol seemed to reduce the absorption of RSV. RSV in liquor exacerbates alcoholic liver injury and has a reduced therapeutic effect, suggesting that the habit of herbal wine use without supervision is risky.

Considering that vaccination with the sIPV and DTaP overlap at the ages of 3 and 4 months in China, to reduce the burden of treatment on parents and increase vaccination coverage rates, we designed a postmarket clinical study of co-administration. The Sabin-strain-based inactivated poliovirus vaccine (sIPV) and the diphtheria-tetanus-acellular pertussis vaccine (DTaP) have been licensed in China for many years. To conduct a clinical study on the safety and immunogenicity of the sIPV when administered concomitantly with the DTaP. The study population was divided into three groups: group 1 was the sIPV+ DTaP concomitant administration group, group 2 was the sIPV inoculation group, and group 3 was the DTaP inoculation group. Blood samples were collected prevaccination and 30 days postvaccination, and serum antibody levels were detected. This study showed that the seropositive and seroconversion rates of type 1, 2 and 3 poliovirus in group 1 were higher than those in group 2, with no statistically significant difference after vaccination (P>0.05). Groups 1 and 3 also showed similar responses for all vaccine antigens except anti-FHA (97.65 (94.09-99.36) vs. 100 (97.89-100)). The geometric mean titers (GMTs) for the DTaP and sIPV among the groups were comparable, and the non-inferiority t test result was P<0.001. The number of local adverse events (AEs) reported in group 1 (29.91%) were larger than those in group 2 (12.39%) and group 3 (21.93%), among which the most common was redness. Similarly, the most common systemic AE was fever. All 5 severe AE (SAE) cases were determined by experts to be unrelated to the vaccines during the study. The evidence of similar seroconversion and safety with co-administered DTaP and sIPV supports the co-administration supports the introduction of a strategy of simultaneous administration of both vaccines into routine infant immunization, and it could increase vaccination coverage and protect more infants from morbidity and mortality from these related diseases. https://clinicaltrials.gov/ct2/show/NCT04054882?term=NCT04054882&cntry=CN&draw=2&rank=1, identifier NCT04054882.

The inactivated quadrivalent influenza vaccine (IIV4) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) have been administered for years and could be administered concomitantly if necessary. However, the immunogenicity and safety of the concomitant administration of these two vaccines have not been well documented, especially in the Chinese population. In this study, 480 participants aged 60 years and older were randomly assigned to the concomitant administration group (C group) or the separate administration group (S group) to receive IIV4 and PPSV23 either concomitantly or separately. Blood samples were collected before and 28 days after each vaccination. The antibodies against four influenza virus strains and twenty-three pneumococcus serotypes were tested. The results showed that the geometric mean titer (GMT) ratios (C group to S group) for the four influenza strains ranged from 0.72 to 0.95, with the lower limits of the 95% confidence intervals (CIs) ranging from 0.51 to 0.75, and the geometric mean concentration (GMC) ratios for the 23 pneumococcal serotypes ranged from 0.80 to 1.00, with the lower limits of 95% CIs ranging from 0.67 to 0.86. All values met the predefined criteria for non-inferiority. The incidence of adverse events was 0.63% in the C group and 1.56% in the S group. No serious adverse events were observed. In conclusion, the immunogenicity of the concomitant administration of IIV4 and PPSV23 was non-inferior to that of the separate administration, and the safety profile was favorable in adults aged 60 years and older in China.

•A porcine circovirus-free human rotavirus vaccine (PCV-free HRV) has been developed.•We compared routine vaccines coadministration with liquid PCV-free vs lyophilized HRV.•We showed non-inferior immune responses for coadministration with PCV-free HRV vs HRV.•We observe comparable safety profiles for liquid PCV-free HRV and lyophilized HRV.•Liquid PCV-free HRV could be used as part of routine vaccination in United States. In response to the detection of porcine circovirus type 1 (PCV-1) in the human rotavirus vaccine (HRV), a PCV-free HRV (no detection of PCV-1 and PCV-2 according to the detection limit of tests used) was developed. Liquid (Liq) PCV-free HRV previously showed immunogenicity and safety profiles comparable to lyophilized (Lyo) HRV. This was a phase 3a, randomized, single-blind study (NCT03207750) conducted in the United States. Healthy infants aged 6–12 weeks received 2 doses (0, 2 months) of either Liq PCV-free HRV or Lyo HRV with routine vaccines (0, 2, 4 months): diphtheria-tetanus-acellular pertussis, hepatitis B and inactivated poliovirus combination vaccine (DTaP-HBV-IPV), monovalent tetanus toxoid-conjugated vaccine against Haemophilus influenzae type b (Hib-TT), and 13-valent pneumococcal conjugate vaccine. Co-primary objectives were: (i) to assess non-inferiority of immune responses to routine vaccine antigens 1 month post-dose 3 following co-administration with Liq PCV-free HRV compared to Lyo HRV; (ii) to rule out a 10% decrease in seroresponse to pertussis antigens after dose 3. Other objectives were to evaluate immunogenicity and safety of HRV vaccines. Of 1272 vaccinated infants, 990 (489 in Liq PCV-free HRV and 501 in Lyo HRV group) were included in the per-protocol set. All statistical criteria were met, thus co-primary objectives were demonstrated. Seroprotection/seropositivity rates in both groups were high: 100% for diphtheria/tetanus, ≥99.3% for HBV, ≥99.8% for polio, ≥99.8% for each pertussis antigen, ≥90.8% for all pneumococcal serotypes except serotype 3 (≥69.1%), and ≥ 97.4% for Hib. Most infants seroconverted for anti-RV antibodies (76.3% of Liq PCV-free HRV and 78.9% of Lyo HRV recipients). Geometric mean concentrations/titers were comparable between groups. Incidences of adverse events and serious adverse events were similar between groups. Routine pediatric vaccines co-administered with Liq PCV-free HRV showed non-inferior immune responses and similar safety profiles to those following co-administration with Lyo HRV.

This study assessed the immunogenicity and safety of a human rotavirus vaccine RIX4414; the effect of co-administration of childhood vaccines on the immune responses was also assessed. Healthy infants aged 6–14 weeks received two doses of RIX4414/placebo concomitantly with the primary childhood vaccination (Infanrix hexa™, Infanrix quinta™,Meningitec™ and/or Prevnar™), respecting the vaccination schedule of each country. Anti-rotavirus IgA seroconversion rate (ELISA cut-off 20U/ml) was measured pre-vaccination and 1–2 months post-Dose 2. Immune response against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, inactivated polio virus, pneumococcal polysaccharide conjugate (France and Germany) and meningococcal group C conjugate vaccines (Spain) were measured approximately 1-month post-Dose 3. An overall anti-rotavirus IgA seroconversion rate of 86.5%(95% CI: 83.9–88.8) was observed in the RIX4414 group 1-month post-Dose 2. The seroconversion rate in Finland and Italy (3 and 5-month schedule) was 94.6%(95% CI: 90.0–97.5) and 92.3%(95% CI: 64.0–99.8), respectively. Immune response to the childhood vaccines was unaffected following co-administration with RIX4414. Reactogenicity profile was similar for RIX4414 and placebo groups. RIX4414 was immunogenic and well tolerated in European infants and the co-administration of routine childhood vaccines with RIX4414 did not negatively impact the immune responses to these vaccines.