Randomized, Double-Blinded, Placebo-Controlled Phase 2 Trial of an Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in Healthy Adults.

BACKGROUND: We evaluated an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for immunogenicity and safety in adults aged 18-59 years. METHODS: In this randomized, double-blinded, controlled trial, healthy adults received a medium dose (MD) or a high dose (HD) of the vaccine at an interval of either 14 days or 28 days. Neutralizing antibody (NAb) and anti-S and anti-N antibodies were detected at different times, and adverse reactions were monitored for 28 days after full immunization. RESULTS: A total of 742 adults were enrolled in the immunogenicity and safety analysis. Among subjects in the 0, 14 procedure, the seroconversion rates of NAb in MD and HD groups were 89% and 96% with geometric mean titers (GMTs) of 23 and 30, respectively, at day 14 and 92% and 96% with GMTs of 19 and 21, respectively, at day 28 after immunization. Anti-S antibodies had GMTs of 1883 and 2370 in the MD group and 2295 and 2432 in the HD group. Anti-N antibodies had GMTs of 387 and 434 in the MD group and 342 and 380 in the HD group. Among subjects in the 0, 28 procedure, seroconversion rates for NAb at both doses were both 95% with GMTs of 19 at day 28 after immunization. Anti-S antibodies had GMTs of 937 and 929 for the MD and HD groups, and anti-N antibodies had GMTs of 570 and 494 for the MD and HD groups, respectively. No serious adverse events were observed during the study period. CONCLUSIONS: Adults vaccinated with inactivated SARS-CoV-2 vaccine had NAb as well as anti-S/N antibody and had a low rate of adverse reactions. CLINICAL TRIALS REGISTRATION: NCT04412538.

Effectiveness and Safety of an Inactivated Enterovirus 71 Vaccine in Children Aged 6-71 Months in a Phase IV Study.

BACKGROUND: Evaluation of a licensed inactivated enterovirus type 71 (EV71) vaccine is needed in a phase IV study with a large population to identify its effectiveness and safety for further application. METHODS: An open-label, controlled trial involving a large population of 155 995 children aged 6-71 months was performed; 40 724 were enrolled in the vaccine group and received 2 doses of inactivated EV71 vaccine at an interval of 1 month, and the remaining children were used as the control group. The EV71-infected cases with hand, foot, and mouth disease were monitored in the vaccine and control groups during a follow-up period of 14 months since the 28th day postinoculation through the local database of the Notifiable Infectious Diseases Network. The effectiveness of the vaccine was estimated by comparing the incidence density in the vaccine group versus that in the control group based upon EV71-infected patients identified via laboratory testing. In parallel, the active and passive surveillance for safety of the vaccine was conducted by home or telephone visits and by using the Adverse Event Following Immunization (AEFI) system, respectively. RESULTS: An overall level of 89.7% (95% confidence interval, 24.0-98.6%) vaccine effectiveness against EV71 infection and a 4.58% rate of reported adverse events were observed. Passive surveillance demonstrated a 0.31% rate of reported common minor reactions. CONCLUSIONS: The clinical protection and safety of the EV71 vaccine were demonstrated in the immunization of a large population. CLINICAL TRIALS REGISTRATION: NCT03001986.

Immunogenicity and Safety of an F-Genotype Attenuated Mumps Vaccine in Healthy 8- to 24-Month-Old Children.

Background: Mumps vaccine immunizations have reduced the incidence of this disease. With the variation of mumps circulating strain, novel vaccine strains are always important. Methods: A 2-center parallel, randomized, double-blind noninferiority trial was performed to compare an F-genotype attenuated mumps vaccine (SP strain) to the A-genotype vaccine (S-79, Jeryl-Lynn strain) in 1080 healthy children aged 8-24 months in Hubei, China. Results: Participants were randomly assigned to receive a high or low dose of the SP or S79 vaccine and then assessed clinically at 30 minutes and 1-28 days postinoculation. No differences in local or systemic reactivity were observed. A similar incidence of severe adverse events associated with the vaccine was observed in the high-dose group and the positive control group. Based on throat swab collections, no viral shedding was present at the 4th and 10th days in any group. Neutralizing and hemagglutination-inhibiting antibody assays with the F- or A-genotype strains showed similar trends in geometric mean titers in the high-dose SP and S79 groups. Increased cytotoxic T lymphocyte responses were observed in all groups. Conclusions: The F-genotype attenuated mumps vaccine is safe, offers immunogenicity against a homologous virus, and is noninferior to the A-genotype vaccine in 8- to 24-month-old children.

[Epidemiological characteristics of mumps in mainland China from 2004 to 2018 and key population for prevention and control].

OBJECTIVE: To investigate the epidemiological characteristics of mumps in mainland China from 2004 to 2018, and to provide data for the key population for prevention and control of mumps. METHODS: The epidemiological characteristics of mumps were analyzed with reference to the data of the cases of mumps reported in the National Scientific Data Sharing Platform for Population and Health and Disease Prevention and Control Bureau of National Health Commission of the People's Republic of China. Descriptive epidemiology was used to analyze the epidemiological characteristics of mumps. RESULTS: A total of 4 272 368 cases of mumps were reported in China during 2004-2018, with an average annual reported incidence rate of 21.44/100 000. A single dose of mumps-containing vaccine was added to the national Expanded Program of Immunization in 2008, but the annual incidence rate ranged from 12.84/100 000 to 35.59/100 000. The second dose of measles, mumps and rubella combined attenuated live vaccine was included in the routine immunization in Beijing, Tianjin and Shanghai, and then the average incidence rate of mumps reported in these three regions dropped to about 10/100 000. From 2004 to 2016, the population aged 3-14 years accounted for 81.16% of all patients with mumps. The children aged 6 years had the highest incidence rate of mumps during 2004-2013. CONCLUSIONS: A single dose of mumps-containing vaccine has no obvious effect on the incidence rate of mumps. Children aged 6 years have the highest incidence rate of mumps. A booster dose of mumps-containing vaccine should be given to preschool children.

Treatment of Skin Reaction Induced by Nivolumab Combined with Radiotherapy in Non-small Cell Lung Cancer: A Case Report.

Skin reaction or dermatological toxicities induced by immunotherapy is common. It usually manifests skin rash or erythema and can be cured by skin lotion or steroid. Nivolumab, a human IgG4 programmed cell death protein 1 (PD-1) inhibitor, blocks T cells activation preventing signal and allows the immune system to clear cancer cells. Nivolumab was approved in the second-line therapy in squamous cell lung cancer by FDA, with less than 10% unusual skin reaction, like sensory neuropathy, peeling skin, erythema multiforme, vitiligo, and psoriasis. Radiotherapy could aggravate this skin reaction through inflammatory response and promotion of immunity. The combined treatment of anti-PD-1 and radiotherapy represented a new promising therapeutic approach in many studies, but the risk of side effects may be high. We reported a patient with advanced squamous cell lung cancer who suffered from serious skin immune-related adverse events when he was treated with nivolumab and radiotherapy. The immune overreaction of the treatment of anti-PD-1 treatment and radiotherapy might cause these serious skin adverse events. Our report warranted careful workup to reduce the risk of side effects by combinative therapy with anti-PD-1 and radiotherapy.

Effects of acupoint-stimulation for the treatment of primary dysmenorrhoea compared with NSAIDs: a systematic review and meta-analysis of 19 RCTs.

BACKGROUND: Primary dysmenorrhoea (PD), defined as painful menses in women with normal pelvic anatomy, is one of the most common gynaecological syndromes. Acupoint-stimulation could potentially be an effective intervention for PD. Our aim was to determine the effectiveness of acupoint-stimulation compared with Non-Steroidal Anti-Inflammatory Drugs (NASIDs) in the treatment of PD. METHODS: Six databases were searched to December 2014. Sixteen studies involving 1679 PD patients were included. We included randomized controlled trials that compared acupoint-stimulation with NASIDs for the treatment of PD. The main outcomes assessed were clinical effectiveness rate, symptom score, visual analogue score, variation in peripheral blood prostaglandin F2α (PGF2α) and side effects. All analyses were performed using Comprehensive Meta-Analysis statistical software. RESULTS: (1) The total efficacy was better than control group: odds ratio = 5.57; 95% confidence interval (95% CI) = 3.96, 7.83; P < 0.00001; (2) The effect of intervention was positive in relieving the severity of PD symptoms: mean difference (MD) = 2.99; 95%CI = 2.49, 3.49; P < 0.00001; (3) No statistical difference existed between two groups in terms of a reduction in the VAS: MD = 1.24; 95%CI = -3.37, 5.85; P = 0.60; (4) The effect of intervention on the variation in peripheral blood PGF2α between two groups was positive: MD = 7.55; 95%CI = 4.29,10.82; P < 0.00001; (5) The side effects of control groups was more than the acupoint-stimulation group: OR = 0.03; 95%CI =0.00,0.22; P = 0.0005. CONCLUSIONS: According to this article, acupoint-stimulation can relieve pain effectively in the treatment of PD and offers advantages in increasing the overall effectiveness.

Bu Shen Tiao Chong recipe restores diminished ovary reserve through the BDNF pathway.

PURPOSE: The purpose of this study was to explore the molecular pathway of BSTCR (Bu Shen Tiao Chong recipe) in retrieving diminished ovary reserve (DOR). METHODS: The DOR model was established through injecting cyclophosphamide and the effect of BSTCR was examined under this background. RESULTS: BSTCR was shown to restore depleted brain-derived neurotrophic factor (BDNF), CDC2, cyclin B, GSH1, and P38 levels as well as impaired oocyte maturation and the higher apoptosis induced in DOR. BSTCR also enhances the response of oocytes to in vitro fertilization, with higher implantation rate, birth rate, and placenta weight. CONCLUSION: BSTCR might exert its beneficial role in oocyte maturation and restore DOR through regulating the BDNF pathway. And this pathway itself is probably through the consequence on several serum hormones such as FSH, E2, Inhibin B, etc.

Prevalence of depressive symptoms and its correlates among medical students in China: a national survey in 33 universities.

We conducted a national survey among medical students in China to estimate the prevalence of depressive symptoms and explore associated risk factors based on an established questionnaire composed of demographic information, life events in the past four weeks before survey, and the validated Chinese version of the 21-item Beck's Depression Inventory (BDI). The mean age of enrolled 9010 students was 20.7 (standard deviation: 1.6) years. BDI scores indicated that 19.9% had depressive symptoms based on the cut-off score of 14. Socioeconomic factors and student characteristics such as male sex, low monthly income per capita, father's poor education background, and higher year of study were associated with higher prevalence of depressive symptoms among medical students. Students who studied in comprehensive universities were more likely to have depressive symptoms compared with those from medical universities. Habitual smoking and alcohol drinking, sleep deprivation, and hospitalization or medication for one week or more in the last four weeks also predisposed students to higher risk of depressive symptoms. Our results indicate that depressive symptoms are becoming a highly prevalent health problem among Chinese medical students. Primary and secondary prevention should be prioritized to tackle this issue based on potential risk factors.

Quality of life in women with cervical precursor lesions and cancer: a prospective, 6-month, hospital-based study in China.

The overall survival of patients with cervical cancer has improved due to detection at an early stage and availability of comprehensive treatments in China. As patients' lives prolonged, it is important to understand their health-related quality of life (QoL) during and after treatment. We used the EQ-5D questionnaire to assess QoL of 194 patients with cervical lesions at Sichuan University West China Second Hospital between May 2010 and January 2011. Patients were surveyed before primary treatment and at 1, 3, and 6 months after primary treatment. Results showed a consistent decline in EQ-5D scores in the spectrum of cervical lesions at each time point after treatment (all P < 0.05). For patients with precursor lesions, there was an increasing trend along the timeline of treatment (P < 0.01). For patients with early-stage cervical cancer, EQ-5D scores declined in the first month (P = 0.01) and gradually increased to higher levels at 6 months post-treatment than those before treatment (P < 0.01). EQ-5D scores followed a similar trend in patients with advanced cervical cancer (P = 0.04), though they did not statistically rebound after 6 months (0.84 ± 0.19 vs. 0.86 ± 0.11, P = 0.62). Regarding advanced cervical cancer, EQ-5D scores for women above 40 years of age appeared to recover more rapidly and reached higher levels than those for women below 40 years (P = 0.03). Caution and extra care are recommended in the early period of cervical cancer treatment given the slight deterioration in the QoL, and in particular, for younger cervical cancer patients. Our study implies that health care providers may need to improve the health-related QoL of cervical cancer patients.

Quantitative Analysis of the Instant and Persistent Inhibition Effects of Maternal Poliovirus Antibodies on the Immune Response in a Phase IV Trial of a Sabin Strain-Based Inactivated Poliovirus Vaccine.

BACKGROUND: An inactivated poliomyelitis vaccine made from Sabin strains (sIPVs) has widely been used in China since 2015. However, the quantitative data on the instant and persistent inhibition effects of maternal poliovirus antibodies on the immune response to sIPV priming and booster vaccination have not been available yet. OBJECTIVE: In this study, we aim to explore and quantify the instant and persistent inhibition effect of maternal poliovirus antibodies on the immune response elicited by sIPV primary and booster vaccination. METHODS: The immunogenicity data consisting of the days 0 and 30 after the prime and booster vaccination of the sIPV in a phase IV trial were pooled for a quantitative analysis of the inhibition effect of maternal poliovirus antibody. The geometric mean ratio (GMR) was calculated using linear regression models, representing that every 2-fold higher maternal poliovirus antibody titer may result in a (1-GMR) lower postimmunization antibody titer. RESULTS: The GMRs for poliovirus types 1, 2, and 3 were 0.79 (0.77-0.82), 0.85 (0.81-0.89), and 0.87 (0.83-0.91) at 30 days after the priming series, 0.86 (0.83-0.89), 0.81 (0.76-0.85), and 0.86 (0.80-0.93) at one year after the priming series, and 0.96 (0.94-0.99), 0.89 (0.86-0.93), and 0.98 (0.93-1.03) at 30 days after the booster dose. The inhibition effect continued to exist until the booster dose 1 year later, and such a persistent inhibition effect was almost attenuated for poliovirus types 1 and 3, and partly reduced for type 2 at 30 days after the booster dose. CONCLUSION: A wider interval between the four sIPV doses might be a consideration for reducing the effect of maternal antibodies and subsequently eliciting and maintaining higher antibody levels to protect against poliovirus transmission and infection at the final stage of polio eradication in the global world. This study's clinical trial registry number is NCT04224519.

Immunogenicity and lot-to-lot consistency of booster shot with Sabin inactivated poliomyelitis vaccine in Chinese children aged 18-24 Months: A phase â £ clinical trial.

BACKGROUND: There has been no data on the immunogenicity and safety of the 4th booster dose of the sIPV immunization in 18-24 months old children in post-marketing studies of large cohort providing with robust results. METHOD: In a phase Ⅳ randomized, double-blinded clinical trial, 1200 participants aged 2 months were immunized with three consecutive doses of sIPV at 2, 3, and 4 months old to complete primary immunization. Out of the 1200 participants, 1129 received the 4th dose of sIPV as booster immunization. Immunogenicity was evaluated in 1100 participants. RESULTS: Seropositive rates of the anti-poliovirus type 1, 2, and 3 neutralizing antibodies were 99.9 %, 98.0 %, 98.2 %, respectively, with GMTs of 557.0, 146.1, 362.0 one year after primary vaccination. After booster vaccination between 18 and 24 months old, the seropositive rates for 3 types all reached 100.0 %, with GMTs of 8343.6, 5039.6, 5492.0, respectively. Particularly for the anti-poliovirus type 2 antibody, the GMT was 230.4 after primary immunization, maintained to 146.1 one year after primary immunization, and increased to as high as 5039.6 after booster vaccination. The GMT ratios between each batch groups after booster immunization were between 0.67 and 1.50, meeting the immunological equivalence criteria. The incidence rate of adverse reaction was 23.0 %, which was comparable to those in the phase Ⅲ trial but had a lower incidence. Furthermore, no SUSAR was reported in this study. INTERPRETATION: In conclusion, as the anti-poliovirus antibodies gradually waned one year post sIPV primary vaccination, especially the type 2 antibody waned to a very low level, suggesting the importance of the booster immunization for children at the age of 18-24 months old. The booster shot can greatly enhance the antibody level and protect children from the potential risk of infection with WPV and VDPV by supplementing the anti-poliovirus type 2 immunity gap in the current real world. Clinic Trial Registration. NCT04224519.

Immune persistence after different polio sequential immunization schedules in Chinese infants.

Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

Extraction optimization of tea saponins from Camellia oleifera seed meal with deep eutectic solvents: Composition identification and properties evaluation.

Traditional organic solvent extractions of tea saponins have many drawbacks. This study aimed to establish an environment-friendly and efficient technology based on deep eutectic solvents (DESs) to extract tea saponins from Camellia oleifera seed meal. The solvent consisting of choline chloride and methylurea was screened as optimal DES. Under the optimal extraction conditions obtained by response surface methodology, the extraction yield of tea saponins reached 94.36 mg/g, which increased by 27% compared with ethanol extraction, while the extraction time was reduced by 50%. Analysis of UV, FT-IR, and UPLC-Q/TOF-MS indicated tea saponins did not alter during DES extraction. Surface activity and emulsification evaluation showed that extracted tea saponins could reduce interfacial tension at the oil-water interface with excellent foamability and foam stability, and they could form nanoemulsions (d32 < 200 nm) with excellent stability. This study provides a suitable approach for the efficient extraction of tea saponins.

Prognostic Factors and Outcomes in Advanced Stage Lung Cancer Patients with COVID-19 Omicron Variant Infection.

Background: We study the characteristics and outcomes in lung cancer patients with COVID-19 Omicron variant infection. Methods: Hospitalized lung cancer patients with advanced-stage disease and laboratory-confirmed COVID-19 Omicron infection were included. Pneumonitis involving at least 25% of lung parenchyma on CT scans, accompanied by symptoms and oxygen saturation below 93%, were criteria for enrollment. Pneumonitis severity was graded using CTCAE v5.0. Treatment included Paxlovid, prednisolone, anticoagulation, and ventilation. Initial data, radiographic findings, and outcomes were compared. Logistic regression was employed to determine risk factors for in-hospital mortality. Results: Fifteen patients (median age: 65 years; 80.0% males) were included. 73.3% improved and were discharged, 20.0% died, and 6.7% remained intubated. Initial symptoms included cough (100.0%), fever (73.3%), and shortness of breath (53.3%). Symptoms resolved in discharged patients. Median fever duration was 3.5 days, and respiratory symptom recovery took 26 days. Three patients died due to respiratory failure from Omicron pneumonia. Lower oxygen saturation, reduced lymphocyte/neutrophil ratio on day 7, and diffuse bilateral lung lesions were poor prognostic factors. Conclusion: This study underscores the importance of prompt intervention and early diagnosis for lung cancer patients infected with the COVID-19 Omicron variant. Lower oxygen saturation, decreased lymphocyte/neutrophil ratio on day 7, and diffuse lung lesions on CT scans were associated with worse outcomes. Clinicians should prioritize timely and comprehensive management to improve survival rates in this population.

Immune persistence of an inactivated poliovirus vaccine derived from the Sabin strain: a 10-year follow-up of a phase 3 study.

Background: In a previous phase 3 clinical trial, we showed that an inactivated poliovirus vaccine derived from the Sabin strain (sIPV) can induce neutralising antibodies against currently circulating and reference wild poliovirus strains. However, the immune persistence of sIPV remains to be evaluated. Methods: In this study, 400 participants who were eligible for an early phase 3 clinical trial (Jan 1, 2012-Aug 31, 2014) in Pingle County, GuanXi Province, China, were initially involved in one site. Of the participants in the previous phase 3 clinical trial, sera of 287, 262, 237, and 207 participants were sampled at the ages of 4, 6, 8, and 10 years, respectively, after the prime-boost regimen. Neutralising antibodies against attenuated Sabin strains were detected using these serum samples to determine immune persistence. The serum neutralising antibodies titre of 1:8 against poliovirus types 1, 2, and 3 is considered to be a seroprotection level for polio. The trial is registered at ClinicalTrials.gov, NCT01510366. Findings: The protective rates against poliovirus types 1, 2, and 3 in the sIPV group were all 100% at 10 years after the booster immunisation, compared with 98.1%, 100%, and 97.1%, respectively, in the wIPV control group after 10 years. After the booster at 18 months, the geometric mean titres (GMTs) of neutralising antibodies against poliovirus types 1, 2, and 3 in the sIPV group were 13,265.6, 7856.7, and 6432.2, respectively, and the GMTs in the control group (inoculated with inactivated poliovirus vaccine derived from wild strain (wIPV)) were 3915.6, 2842.6, and 4982.7, respectively. With increasing time after booster immunisation, the GMTs of neutralising antibodies against poliovirus types 1, 2, and 3 gradually decreased in both the sIPV and wIPV groups. At the age of ten years, the GMTs of neutralising antibodies against poliovirus types 1, 2, and 3 in the sIPV group were 452.3, 392.8, and 347.5, respectively, and the GMTs in the wIPV group 108.5, 154.8, and 229.3, respectively, which were still at a higher-than-protective level (1:8). Interpretation: Both sIPV and wIPV maintained sufficiently high immune persistence against poliovirus types 1, 2, and 3 for at least 10 years after booster immunisation. Funding: Yunnan Provincial Science and Technology Department, the Bill and Melinda Gates Foundation, the National High-tech Research and Development Program, the National International Science and Technology Cooperation Project, the Yunnan Application Basic Research Project, the Innovation Team Project of Xie He, the Yunnan International Scientific and Technological Cooperation Project, and the Medical and Technology Innovation Project of Xie He.

Rotavirus and Norovirus Infections in Children Under 5 Years Old with Acute Gastroenteritis in Southwestern China, 2018-2020.

OBJECTIVE: Rotaviruses and noroviruses are important causes of acute gastroenteritis in children. While previous studies in China have mainly focused on rotavirus, we investigated the incidence of norovirus in addition to rotavirus in Southwestern China. METHODS: From January 2018 to December 2020, cases of rotavirus or norovirus infections among children under five ages with acute gastroenteritis were evaluated retrospectively. RESULTS: The detection rate of rotavirus was 24.5% (27,237/111,070) and norovirus was 26.1% (4649/17,797). Among 17,113 cases submitted for dual testing of both rotavirus and norovirus, mixed rotavirus/norovirus infections were detected in 5.0% (859/17,113) of cases. While there was no difference in norovirus incidence in outpatient compared to hospitalized cases, rotavirus was detected two times more in outpatients compared to hospitalized cases (26.6% vs.13.6%; P < 0.001). Both rotavirus and norovirus infections peaked in children aged 12-18 months seeking medical care with acute gastroenteritis (35.6% rotavirus cases; 8439/23,728 and 32.5% norovirus cases; 1660/5107). Rotavirus infections were frequent between December and March of each year while norovirus was detected earlier from October to December. Our results showed significant correlation between virus detection and environmental factors such as average monthly temperature but not relative humidity. In addition, we observed a reduction in the detection rates of rotavirus and norovirus at the beginning of the SARS-CoV-2 pandemic in 2020. CONCLUSION: Our results indicate that rotavirus and norovirus are still important viral agents in pediatric acute gastroenteritis in Southwestern China.

Safety evaluation on concomitant immunization with inactivated poliomyelitis vaccine produced from Sabin strains and other vaccines (from 2015 to 2020).

OBJECTIVE: To evaluate the safety of concomitantly administering inactivated poliomyelitis vaccine produced from Sabin strains (sIPVs) with other vaccines. METHODS: A descriptive analysis was carried out on adverse events following immunization (AEFI) based on the administration of sIPV alone or concomitant with other vaccines (from 2015 to 2020) using data from the national AEFI surveillance system of China (CNAEFIS). All adverse reactions (ADRs) of the concomitant immunization were coded using a medical dictionary for regulatory activities (MedDRA) before comparison. RESULTS: The CNAEFIS reported a total of 9130 sIPV-related AEFI cases, including 6842 AEFI cases collected after immunization with sIPV alone and 2288 AEFI cases collected after immunization of sIPV concomitant with other vaccines. The combination of sIPV with diphtheria, tetanus and pertussis vaccine (DTaP) was correlated with the highest frequency of AEFI, which accounted for 53.50% of all 2288 AEFI cases. After MedDRA-based coding, the most frequent ADR was fever (70.18%), followed by erythema and swelling at the injection site (6.95%), induration at the injection site (3.85%), dermatitis allergy (3.56%) and urticaria (1.55%). A statistically significant difference (P < .001) was found between sIPV immunization and sIPV immunization concomitant with other vaccines for general reactions (95.36% and 93.22%, respectively) and abnormal reactions (4.64% and 6.78%, respectively). CONCLUSION: No new safety signal is found for sIPV administered concomitantly, although its administration with other vaccines may increase the occurrence of abnormal reactions. Vaccine manufacturers should focus on the safety of administering sIPV with DTaP and carry out relevant clinical studies when necessary.

Immunogenicity and safety of the inactivated enterovirus 71 vaccine administered concomitantly with the measles-rubella vaccine in infants aged 8 months in China: A noninferiority randomized controlled trial.

BACKGROUND: To evaluate the immunogenicity and safety of simultaneous administration of the enterovirus 71 (EV71) vaccine with the measles and rubella (MR) combined vaccine. METHODS: In this phase 4, randomized, open-label and noninferiority study, a total of 680 infants aged 8 months were enrolled and assigned to the simultaneous administration group (infants received the first dose of EV71 vaccine and MR vaccine on Day 0, and the second dose of EV71 vaccine on Day 28), or the separate administration groups (EV71 group: infants received two doses of EV71 vaccine on Day 0 and Day 28, respectively; MR group: infants received MR vaccine on Day 0). Blood sample was obtained on Day 0 and Day 56 to measure antibody responses to each of the antigens in terms of antibody titer or concentration, respectively. Local and systemic adverse reactions (ARs) and other adverse events (AEs) following each dose were monitored and compared among groups. RESULTS: After vaccination, simultaneous administration group showed similar seroconversion rates of antibody against EV71(97.9%), measles (97.4%), and rubella (94.3%) compared to EV71 group (99.6% for anti-EV71) or MR group (98.4% for anti-measles and 98.9% for anti-rubella, respectively). Noninferiority was demonstrated for all antibodies as the lower limits of two-sided 97.5% confidence intervals (CIs) of the difference in seroconversion rates between simultaneous administration group and separate administration groups were above the predefined margin of -10%. Additionally, the adverse reaction rates were comparable among groups (54.4% in the simultaneous group versus 43.9% in the MR group versus 52.6% in the EV71 group). CONCLUSION: Antibody responses induced by simultaneous administration of EV71 vaccine with MR vaccine were robust and noninferior to those by single administration alone. Like the previous findings by single administration alone, simultaneous administration demonstrated comparable reactogenicity and safety profiles.

Reduced mucosal immunity to poliovirus after cessation of trivalent oral polio vaccine.

The switch from using only trivalent oral polio vaccine (tOPV) to sequential schedules combining inactivated poliovirus vaccine (IPV) and bivalent oral polio vaccine (bOPV) for polio vaccination will cause changes to mucosal immunity against polio in infants, which plays an important role in preventing the poliovirus spread. Here, we analyzed mucosal immunity against poliovirus in the intestine during different sequential vaccination schedules. We conducted clinical trials in Guangxi Province, China on 1,200 2-month-old infants who were randomly assigned to one of three vaccination schedule groups: IPV-bOPV-bOPV, IPV-IPV-tOPV, and IPV-IPV-bOPV, with vaccine doses administered at 8, 12, and 16 weeks of age. Stool samples were collected from 10% of participants in each group before administration of the second vaccine doses and at 1, 2, and 4 weeks after the administrations of the second and third vaccine doses. Immunoglobulin A (IgA) in the stool samples was measured to analyze the mucosal immune response in the intestine. Because of the absence of poliovirus type 2 in bOPV, the vaccination schedule of IPV-IPV-bOPV did not sufficiently raise intestinal mucosal immunity against poliovirus type 2, although some cross-immunity was seen. The level of intestinal mucosal immunity was related to shedding status; shedders could produce intestinal mucosa IgA more quickly. The intestinal mucosal immunity level was not related to serum neutralizing antibody level. In the combined sequential vaccination schedule of IPV and bOPV, the risk of circulating vaccine-derived poliovirus type 2 (cVDPV2) may be increased owing to insufficient intestinal mucosal immunity against poliovirus type 2.

Intensified antibody response elicited by boost suggests immune memory in individuals administered two doses of SARS-CoV-2 inactivated vaccine.

Neutralizing antibodies in the subjects of an inactivated SARS-CoV-2 vaccine clinical trial showed a decreasing trend over months. An investigation studying the third immunization suggested that the waning of neutralizing antibodies in individuals administered two doses of inactivated vaccine does not mean the disappearance of immunity.