Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity.

During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

Generation of human vascularized and chambered cardiac organoids for cardiac disease modelling and drug evaluation.

Human induced pluripotent stem cell (hiPSC)-derived cardiac organoids (COs) have shown great potential in modelling human heart development and cardiovascular diseases, a leading cause of global death. However, several limitations such as low reproducibility, limited vascularization and difficulty in formation of cardiac chamber were yet to be overcome. We established a new method for robust generation of COs, via combination of methodologies of hiPSC-derived vascular spheres and directly differentiated cardiomyocytes from hiPSCs, and investigated the potential application of human COs in cardiac injury modelling and drug evaluation. The human COs we built displayed a vascularized and chamber-like structure, and hence were named vaschamcardioids (vcCOs). These vcCOs exhibited approximately 90% spontaneous beating ratio. Single-cell transcriptomics identified a total of six cell types in the vcCOs, including cardiomyocytes, cardiac precursor cells, endothelial cells, fibroblasts, etc. We successfully recaptured the processes of cardiac injury and fibrosis in vivo on vcCOs, and showed that the FDA-approved medication captopril significantly attenuated cardiac injury-induced fibrosis and functional disorders. In addition, the human vcCOs exhibited an obvious drug toxicity reaction to doxorubicin in a dose-dependent manner. We developed a three-step method for robust generation of chamber-like and vascularized complex vcCOs, and our data suggested that vcCOs might become a useful model for understanding pathophysiological mechanisms of cardiovascular diseases, developing intervention strategies and screening drugs.

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.

BubR1 controls starvation-induced lipolysis via IMD signaling pathway in Drosophila.

Lipolysis, the key process releasing fat acids to generate energy in adipose tissues, correlates with starvation resistance. Nevertheless, its detail mechanisms remain elusive. BubR1, an essential mitotic regulator, ensures proper chromosome alignment and segregation during mitosis, but its physiological functions are largely unknown. Here, we use Drosophila adult fat body, the major lipid storage organ, to study the functions of BubR1 in lipolysis. We show that both whole body- and fat body-specific BubR1 depletions increase lipid degradation and shorten the lifespan under fasting but not feeding. Relish, the conserved regulator of IMD signaling pathway, acts as the downstream target of BubR1 to control the expression level of Bmm and modulate the lipolysis upon fasting. Thus, our study reveals new functions of BubR1 in starvation-induced lipolysis and provides new insights into the molecular mechanisms of lipolysis mediated by IMD signaling pathway.

Integrative Analysis of Morphine-Induced Differential Circular RNAs and ceRNA Networks in the Medial Prefrontal Cortex.

Circular RNAs (circRNAs) are a novel type of non-coding RNAs. Despite the fact that the functional mechanisms of most circRNAs remain unknown, emerging evidence indicates that circRNAs could sponge microRNAs (miRNAs), bind to RNA binding proteins (RBP), and even be translated into protein. Recent research has demonstrated the crucial roles played by circRNAs in neuropsychiatric disorders. The medial prefrontal cortex (mPFC) is a crucial component of drug reward circuitry and exerts top-down control over cognitive functions. However, there is currently limited knowledge about the correlation between circRNAs and morphine-associated contextual memory in the mPFC. Here, we performed morphine-induced conditioned place preference (CPP) in mice and extracted mPFC tissue for RNA-sequencing. Our study represented the first attempt to identify differentially expressed circRNAs (DEcircRNAs) and mRNAs (DEmRNAs) in the mPFC after morphine-induced CPP. We identified 47 significantly up-regulated DEcircRNAs and 429 significantly up-regulated DEmRNAs, along with 74 significantly down-regulated DEcircRNAs and 391 significantly down-regulated DEmRNAs. Functional analysis revealed that both DEcircRNAs and DEmRNAs were closely associated with neuroplasticity. To further validate the DEcircRNAs, we conducted qRT-PCR, Sanger sequencing, and RNase R digestion assays. Additionally, using an integrated bioinformatics approach, we constructed ceRNA networks and identified critical circRNA/miRNA/mRNA axes that contributed to the development of morphine-associated contextual memory. In summary, our study provided novel insights into the role of circRNAs in drug-related memory, specifically from the perspective of ceRNAs.

Porphyromonas gingivalis induces an inflammatory response via the cGAS-STING signaling pathway in a periodontitis mouse model.

Periodontitis is an inflammatory disease initiated by periodontopathogenic bacteria in the dental plaque biofilms. Understanding the role of Porphyromonas gingivalis (P. gingivalis), a keystone pathogen associated with chronic periodontitis, in the inflammatory response is crucial. Herein, we investigated whether P. gingivalis infection triggers the expression of the type I IFN gene and various cytokines and leads to activation of the cGAMP synthase-stimulator of IFN genes (cGAS-STING) pathway both in vitro and in a mouse model. Additionally, in an experimental model of periodontitis using P. gingivalis, StingGt mice showed lower levels of inflammatory cytokines and bone resorption than wild-type mice. Furthermore, we report that a STING inhibitor (SN-011) significantly decreased inflammatory cytokine production and osteoclast formation in a periodontitis mouse model with P. gingivalis. In addition, STING agonist (SR-717) -treated periodontitis mice displayed enhanced macrophage infiltration and M1 macrophage polarization in periodontal lesions compared with that in vehicle-treated periodontitis mice. In conclusion, our results demonstrate that the cGAS-STING signaling pathway may be one of the key mechanisms crucial for the P. gingivalis-induced inflammatory response that leads to chronic periodontitis.

The 5-HT7 receptors in the VLO contribute to the development of morphine-induced behavioral sensitization in rats.

The 5-hydroxytryptamine 7 receptor (5-HT7R) is one of the most recently cloned serotonin receptors which have been implicated in many physiological and pathological processes including drug addiction. Behavioral sensitization is the progressive process during which re-exposure to drugs intensified the behavioral and neurochemical responses to drugs. Our previous study has demonstrated that the ventrolateral orbital cortex (VLO) is critical for morphine-induced reinforcing effect. The aim of the present study was to investigate the effect of 5-HT7Rs in the VLO on morphine-induced behavioral sensitization and their underlying molecular mechanisms. Our results showed that a single injection of morphine, followed by a low challenge dose could induce behavioral sensitization. Microinjection of the selective 5-HT7R agonist AS-19 into the VLO during the development phase significantly increased morphine-induced hyperactivity. Microinjection of the 5-HT7R antagonist SB-269970 suppressed acute morphine-induced hyperactivity and the induction of behavioral sensitization, but had no effect on the expression of behavioral sensitization. In addition, the phosphorylation of AKT (Ser 473) was increased during the expression phase of morphine-induced behavioral sensitization. Suppression of the induction phase could also block the increase of p-AKT (Ser 473). In conclusion, we demonstrated that 5-HT7Rs and p-AKT in the VLO at least partially contribute to morphine-induced behavioral sensitization.

Phosphorylation of Neurofilament Light Chain in the VLO Is Correlated with Morphine-Induced Behavioral Sensitization in Rats.

Neurofilament light chain (NF-L) plays critical roles in synapses that are relevant to neuropsychiatric diseases. Despite postmortem evidence that NF-L is decreased in opiate abusers, its role and underlying mechanisms remain largely unknown. We found that the microinjection of the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) into the ventrolateral orbital cortex (VLO) attenuated chronic morphine-induced behavioral sensitization. The microinjection of TSA blocked the chronic morphine-induced decrease of NF-L. However, our chromatin immunoprecipitation (ChIP)-qPCR results indicated that this effect was not due to the acetylation of histone H3-Lysine 9 and 14 binding to the NF-L promotor. In line with the behavioral phenotype, the microinjection of TSA also blocked the chronic morphine-induced increase of p-ERK/p-CREB/p-NF-L. Finally, we compared chronic and acute morphine-induced behavioral sensitization. We found that although both chronic and acute morphine-induced behavioral sensitization were accompanied by an increase of p-CREB/p-NF-L, TSA exhibited opposing effects on behavioral phenotype and molecular changes at different addiction contexts. Thus, our findings revealed a novel role of NF-L in morphine-induced behavioral sensitization, and therefore provided some correlational evidence of the involvement of NF-L in opiate addiction.

Promises and challenges of cardiac organoids.

Cardiovascular diseases are currently the main cause of death. The study of the pathogenesis and treatment of these diseases is still a major challenge. Traditional 2D cultured cells and animal models have certain limitations. Heart organoids as models can simulate the structure and function of the body, providing a new research strategy. This paper mainly discusses the development of organoids and their application in the study of the cardiac developmental process, drug screening and treatment of genetic and non-genetic diseases, concluding with their strengths and weaknesses.

Influence of in-Vehicle Audio Warning on Drivers' Eye-Movement and Behavior at Flashing Light-Controlled Grade Crossings.

OBJECTIVE: This study aims to evaluate the effect of in-vehicle audio warning at flashing-light-controlled grade crossings based on driving simulation and eye-tracking systems. BACKGROUND: Collisions at flashing-light-controlled grade crossings have severe consequences. In-vehicle audio warning has the potential to regulate driver behavior. However, whether this improvement occurs through priming drivers' visual search patterns is not yet clear. METHOD: Drivers' visual activity and behaviors were recorded. The effect of a warning was tested with a series of flashing light trigger times (FLTTs) ranging from 2s to 6s with a 1s increment. Different driving conditions (i.e., clear and fog) and driver experience were considered in the experiment design. RESULTS: Warnings could guide the allocation of both overt and covert attention, as well as raise drivers' situation awareness, manifesting as the enhanced perception of signs and better understanding of the flashing red light. Significant improvement in the stop-compliance rate was found in warning scenarios, particularly with a late FLTT. The decreased saccade duration and increased fixation duration on the signal implied a dilemma-zone effect when the FLTT was lower than 4s. Furthermore, reduced fixation duration on signs and signals was found in foggy conditions. Non-professional drivers had a wider search range than their counterparts. CONCLUSION: In-vehicle audio warning is an effective countermeasure for improving crossing safety by optimizing visual search strategy. APPLICATION: In-vehicle audio warnings warrant promotion at grade crossings based on the driver assistance system.

Triboelectrostatic charging behavior of pulse particles in a vortex flow tribocharger.

Triboelectrostatic separation (TES) has shown its great potential in dry fractionation of food ingredients. The principle of the TES technique is straightforward, i.e., charging particles through interactions of particle-particle and/or particle-wall of the contact material, followed by the effect of an electric field. However, optimization of TES efficiency is complex due to obscure understandings, unknowns, and inconsistencies in the charging mechanism between the tribocharger and the agro-food materials. To broaden the design and applications of the TES technique and shed some light on the charging mechanism, experiments were conducted in a vortex flow tribocharger made of three different materials (Copper, Stainless Steel, and PTFE) to investigate the chargeability of five type of selected pulses particles. A Faraday cup measurement system was applied to measure the electric charge of the particles collected at the core and wall regions of the tribocharger. The charges of the pulse particles induced by the vibratory feeder were also measured to verify the chargeability of the particles. Ideal charging material was suggested by comparing the specific charge of particles using the three vessels. A simple "wave propagation" mode based on the vortex flow dynamics has been proposed with an attempt to explore the role of particle-particle and particle-wall interactions on the triboelectrostatic charging.

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.

An improved automated braking system for rear-end collisions: A study based on a driving simulator experiment.

INTRODUCTION: To assist drivers in avoiding rear-end collisions, many early warning systems have been developed up to date. Autonomous braking technology is also used as the last defense to ensure driver's safety. METHOD: By taking the accuracy and timeliness of automatic system control into account, this paper proposes a rear-end Real-Time Autonomous Emergency Braking (RTAEB) system. The system inserts brake intervention based on drivers' real-time conflict identification and collision avoidance performance. A driving simulator-based experiment under different traffic conditions and deceleration scenarios were conducted to test the different thresholds to trigger intervention and the intervention outcomes. The system effectiveness is verified by four evaluation indexes, including collision avoidance rate, accuracy rate, sensitivity rate, and precision rate. RESULTS: The results showed that the system could help avoid all collision events successfully and enlarge the final headway distance, and a TTC threshold of 1.5 s and a maximum deceleration threshold of -7.5 m/s2 could achieve the best collision avoidance effect. The paper demonstrates the situations that are more inclined to trigger the RTAEB (i.e., a sudden brake of the leading vehicle and a small car-following distance). Moreover, the study shows that driver characteristics (i.e., gender and profession) have no significant association with system trigger. Practical Applications: The study suggests that development of collision avoidance systems design should pay attention to both the real-time traffic situation and drivers' collision avoidance capability under the present situation.

The impact of different IPV-OPV sequential immunization programs on hepatitis A and hepatitis B vaccine efficacy.

In recent years, the Global Polio Eradication Initiative has gradually implemented a global shift in polio immunization programs. Few studies cover polio immunization program impacts on the efficacy of other vaccines. This study investigated whether polio immunization programs affected hepatitis A (HepA) and hepatitis B (HepB) vaccination efficacy. Serum samples were collected from 968 infants before the first dose of polio vaccine, 28 days after completing primary polio immunization, and at 24 months old. Infants were classified into six polio immunization program groups: 1sIPV+2bOPV, 2sIPV+1bOPV, 2sIPV+1tOPV, 1cIPV+2bOPV, 2cIPV+1bOPV, and 2cIPV+1tOPV (sIPV: Sabin inactivated poliovirus vaccine; cIPV: Salk inactivated poliovirus vaccine; b, bivalent; t, trivalent; OPV, oral polio vaccine). No significant differences existed in antibody titers against HepA virus (anti-HAV) among the polio immunization program groups at any of the three time points (pre-first dose [p = 0.412], 28 days after primary immunization [p = 0.676], 24 months old [p = 0.556]). Before the first dose (p = 0.178) and at age 24 months (p = 0.987), no significant differences existed in HepB surface antibody (HBsAb) titers between the six polio immunization program groups). Twenty-eight days after primary immunization, no significant difference existed in HBsAb titers between groups after Bonferroni correction. Following HepA and HepB immunization, anti-HAV and HBsAb positivity reached > 98% in all groups, reflecting effective immunization. Our data suggest that different polio immunization programs did not affect HepA and HepB vaccine efficacy; HepA and HepB vaccines maintained high effectiveness irrespective of polio immunization program. This trial was registered on Clinical Trials.gov: NCT03614702.

Genetic Polymorphism of 24 Autosomal STR in the Population of Rwanda.

Rwanda is one of the smallest countries of Africa, where forensic genetic studies are rarely being conducted and very few DNA databases have been developed. Short tandem repeats (STRs) polymorphisms were investigated in 505 unrelated Rwandese by using the HUMDNA TYPING (Yanhuang) Kit. The following STRs were targeted: D3S1358, D13S317, D7S820, D16S539, SE33, D10S1248, D5S818, D21S11, TPOX, D1S1656, D6S1043, D19S433, D22S1045, D8S1179, Penta E, D2S441, D12S391, D2S1338, vWA, Penta D, TH01, D18S51, CSF1PO and FGA. The purpose of this study was to elucidate the genetic diversity and explore the potential of applying these 24 STR in 505 Rwandan population in forensics. A total of 360 alleles, with corresponding allele frequencies in the range from 0.001 to 0.442, were found in the Rwandan population. SE33 presented the highest polymorphism (PIC=0.921) among these 24 loci, whereas D13S317 presented the lowest one (PIC=0.671). No deviation from the Hardy-Weinberg equilibrium was observed for any of the 24 loci. The forensic parameters, including the combined power of discrimination (PD and the combined exclusion power, have demonstrated that this panel of 24 STRs is highly informative and useful for forensic applications such as individuals' identification and paternity tests. Additionally, the genetic distances between Rwanda population and other 24 published populations were calculated based on 8 overlapping loci with the polygenetic tree revealing significant clusters in the populations associated with their geographic locations and their historical relationship.

Intermittent Starvation Promotes Maturation of Human Embryonic Stem Cell-Derived Cardiomyocytes.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) represent an infinite cell source for cardiovascular disease modeling, drug screening and cell therapy. Despite extensive efforts, current approaches have failed to generate hPSC-CMs with fully adult-like phenotypes in vitro, and the immature properties of hPSC-CMs in structure, metabolism and electrophysiology have long been impeding their basic and clinical applications. The prenatal-to-postnatal transition, accompanied by severe nutrient starvation and autophagosome formation in the heart, is believed to be a critical window for cardiomyocyte maturation. In this study, we developed a new strategy, mimicking the in vivo starvation event by Earle's balanced salt solution (EBSS) treatment, to promote hPSC-CM maturation in vitro. We found that EBSS-induced starvation obviously activated autophagy and mitophagy in human embryonic stem cell-derived cardiomyocytes (hESC-CMs). Intermittent starvation, via 2-h EBSS treatment per day for 10 days, significantly promoted the structural, metabolic and electrophysiological maturation of hESC-CMs. Structurally, the EBSS-treated hESC-CMs showed a larger cell size, more organized contractile cytoskeleton, higher ratio of multinucleation, and significantly increased expression of structure makers of cardiomyocytes. Metabolically, EBSS-induced starvation increased the mitochondrial content in hESC-CMs and promoted their capability of oxidative phosphorylation. Functionally, EBSS-induced starvation strengthened electrophysiological maturation, as indicated by the increased action potential duration at 90% and 50% repolarization and the calcium handling capacity. In conclusion, our data indicate that EBSS intermittent starvation is a simple and efficient approach to promote hESC-CM maturation in structure, metabolism and electrophysiology at an affordable time and cost.

The Safety, Immunogenicity, and Immunopersistence of Hepatitis A Vaccine in HBs-Ag-Positive Participants: A Retrospective Study.

Objectives: To compare the safety, immunogenicity, and immune persistence of hepatitis A (HA) vaccines between HBs-Ag-positive and -negative participants. Method: 9000 participants were enrolled in the phase IV study of live attenuated HA (HA-L) or inactivated HA (HA-I) vaccines. The HBs-Ag-positive subjects were detected and became an independent observation group. Adverse reactions (ARs), geometric mean concentrations (GMCs) and seroconversion rates (SRs) of the vaccines were analyzed at five time points until three years after vaccination. Results: 120 HBs-Ag-positive subjects were screened out, only 1 participant had grade 1 experienced ARs after HA-L injection. Except the time point of two years, the SRs of HBs-Ag-positive group were 100% for both vaccines. The GMCs were not statistically different between HBs-Ag-positive and -negative groups after the HA-L vaccination. The logarithmically transformed GMCs for HBs-Ag-positive and -negative groups were 3.21 mIU/mL (95% CI, 2.03-4.39 mIU/mL) and 2.95 mIU/mL (95% CI, 2.88-3.02 mIU/mL) 28 days after the HA-L vaccination, respectively. Conclusions: Both HA-L and HA-I vaccines were safe for HBs-Ag-positive participants and may provide an excellent long-term protection against HAV in this study. The results indicated that people positive or negative for HBs-Ag can receive both HA-L and HA-I vaccines (ClinicalTrials.gov number, NCT02601040).

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.

Post hoc analysis of two clinical trials to compare the immunogenicity and safety of different polio immunization schedules in Chinese infants.

BACKGROUND: A comparative analysis of the immunogenicity and safety of different poliovirus immunization schedules in Chinese infants is imperative to guide the administration of efficient strategies for the eradication of poliomyelitis. METHODS: A post hoc analysis was conducted with the data from two poliovirus vaccine clinical trials involving a combined total of 2,400 infants aged 60-90 days. Trivalent oral poliovirus vaccine (tOPV), bivalent oral poliovirus vaccine (bOPV), Sabin strain-based inactivated poliovirus vaccine (sIPV), and conventional inactivated poliovirus vaccine (cIPV) were used in different schedules, the immunogenicity and safety of which were compared 28 days after the last of three doses. RESULTS: In a per-protocol set analysis, the tOPV-tOPV-tOPV schedule induced seroconversion in 99.1%, 98.2%, and 96.0% of the inoculated infants for poliovirus type I, II, and III, respectively. The seroconversions for poliovirus types I and III were each almost 100% after immunization with the cIPV-bOPV-bOPV, sIPV-sIPV-bOPV, cIPV-cIPV-bOPV, sIPV-sIPV-tOPV, cIPV-cIPV-tOPV, or sIPV-bOPV-bOPV schedule. However, the schedules that used one IPV dose followed by two (poliovirus type I and III) bOPV doses failed to induce high-level immunity against type II poliovirus. IPV-related schedules were associated with a slightly higher incidence of adverse events (AEs). CONCLUSIONS: If the capacity of IPV can be increased, two or more doses of IPV should be administered before vaccination with bOPV in a sequential schedule to improve immunity against type II poliovirus.