ABSTRACT
Groundwater contaminated by benzene and toluene is a common issue, posing a threat to the ecosystems and human health. The removal of benzene and toluene under sulfate-reducing condition is well known, but how the bacterial community shifts during this process remains unclear. This study aims to evaluate the shift in bacterial community structure during the biodegradation of benzene and toluene under sulfate-reducing condition. In this study, groundwater contaminated with benzene and toluene were collected from the field and used to construct three artificial samples: Control (benzene 50 mg/L, toluene 1.24 mg/L, sulfate 470 mg/L, and HgCl2 250 mg/L), S1 (benzene 50 mg/L, toluene 1.24 mg/L, sulfate 470 mg/L), and S2 (benzene 100 mg/L, toluene 2.5 mg/L, sulfate 940 mg/L). The contaminants (benzene and toluene), geochemical parameters (sulfate, ORP, and pH), and bacterial community structure in the artificial samples were monitored over time. By the end of this study (day 90), approximately 99% of benzene and 96% of toluene could be eliminated in both S1 and S2 artificial samples, while in the Control artificial sample the contaminant levels remained unchanged due to microbial inactivation. The richness of bacterial communities initially decreased but subsequently increased over time in both S1 and S2 artificial samples. Under sulfate-reducing condition, key players in benzene and toluene degradation were identified as Pseudomonas, Janthinobacterium, Novosphingobium, Staphylococcus, and Bradyrhizobium. The results could provide scientific basis for remediation and risk management strategies at the benzene and toluene contaminated sites.
ABSTRACT
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.
ABSTRACT
Silkworm silks show increasing potential in applications of bioengineering, sensors, optics, electronics, and actuators. However, their inherent irregular morphologies, structures, and properties greatly hinder the translation of these technologies to commercial applications. Herein, we report a facile and comprehensive strategy to fabricate high-performance silk materials by spinning silkworms artificially via a multi-task and high-efficiency centrifugal reeling technique. With this strategy, centrifugally reeled silks (CRSs) with long-uniform morphologies, excellent strength (844.83 ± 319.48 MPa), high toughness (121.07 ± 35.31 MJ m-3), and outstanding Young's modulus (27.72 ± 12.61 GPa) are developed. Remarkably, the maximum strength (1.45 GPa) of CRS is 3 times that of cocoon silk and even comparable to spider silk. Moreover, the centrifugal reeling technique realizes the one-step preparation of centrifugally reeled silk yarn (CRSY) from spinning silkworm, and the CRSYs show higher strength (877.38 ± 377.23 MPa) and superior torsional recovery performances. Furthermore, these CRSY-based soft pneumatic actuators (SPAs) exhibit light weight, high-loading capability, easy programmability in strength and motions, and fast responses, and therefore outperform currently reported elastomer-based SPAs, showing promising applications in flexible sensors, artificial muscles, and soft robotics. This work also provides a new guide for producing high-performance silks from silk-secreting insects and arthropods.
Subject(s)
Bombyx , Silk , Animals , Silk/chemistry , Bombyx/chemistry , Elastic Modulus , Bioengineering , Biomedical EngineeringABSTRACT
Pertussis, caused by the gram-negative bacterium Bordetella pertussis, is a highly contagious respiratory disease. Intranasal vaccination is an ideal strategy to prevent pertussis, as the nasal mucosa represents the first-line barrier to B. pertussis infection. The current intramuscular acellular pertussis (aP) vaccines elicit strong antibody and Th2-biased responses but not necessary cellular and mucosal immunity. Here, we formulated two cyclic dinucleotide (CDN)-adjuvanted aP subunit vaccines, a mammalian 2',3'-cGAMP-adjuvanted aP vaccine and a bacterial-derived c-di-GMP-adjuvanted aP vaccine, and evaluated their immunogenicity in a mouse model. We found that the aP vaccine alone delivered intranasally (IN) induced moderate systemic and mucosal humoral immunity but weak cellular immunity, whereas the alum-adjuvanted aP vaccine administered intraperitoneally elicited higher Th2 and systemic humoral immune responses but weaker Th1 and Th17 and mucosal immune responses. In contrast, both CDN-adjuvanted aP vaccines administered via the IN route induced robust humoral and cellular immunity systemically and mucosally. Furthermore, the c-di-GMP-adjuvanted aP vaccine generated better antibody production and stronger Th1 and Th17 responses than the 2',3'-cGAMP-adjuvanted aP vaccine. In addition, following B. pertussis challenge, the group of mice that received IN immunization with the c-di-GMP-adjuvanted aP vaccine showed better protection than all other groups of vaccinated mice, with decreased inflammatory cell infiltration in the lung and reduced bacterial burden in both the upper and lower respiratory tracts. In summary, the c-di-GMP-adjuvanted aP vaccine can elicit a multifaceted potent immune response resulting in robust bacterial clearance in the respiratory tract, which indicates that c-di-GMP can serve as a potential mucosal adjuvant for the pertussis vaccine.
Subject(s)
Bordetella pertussis , Whooping Cough , Adjuvants, Immunologic , Animals , Cyclic GMP/analogs & derivatives , Disease Models, Animal , Immunization , Mammals , Mice , Pertussis Vaccine , Vaccination/methods , Whooping Cough/prevention & controlABSTRACT
In this research, centrifugally spun ultrafine composite starch/polyvinyl alcohol (ST/PVA) fibers with high water stability were prepared by cross-linking with a mixture of glutaraldehyde and formic acid in the form of vapor phase. The effect of cross-linking temperature combined with time on the water stability, crystal structure, and thermal properties of fibers was investigated to obtain the optimum parameters. On this basis, we further prepared Ag-loaded ST/PVA fibers with different contents of nano silver. The structure and properties of Ag-loaded fibers, which cross-linked under the optimum parameters, were analyzed. As a result, the Ag-loaded fibers exhibited excellent water stability and mechanical properties and possessed inhibition zone diameters of 3 and 2 mm to Escherichia coli and Staphylococcus. aureus, respectively. The antibacterial property of the Ag-loaded ST/PVA fibers provided a new route for developing less costly antibacterial fiber materials in the future.
ABSTRACT
The Above Ground Biomass (AGB) of seaweeds is the most fundamental ecological parameter as the material and energy basis of intertidal ecosystems. Therefore, there is a need to develop an efficient survey method that has less impact on the environment. With the advent of technology and the availability of popular filming devices such as smartphones and cameras, intertidal seaweed wet biomass can be surveyed by remote sensing using popular RGB imaging sensors. In this paper, 143 in situ sites of seaweed in the intertidal zone of GouQi Island, ShengSi County, Zhejiang Province, were sampled and biomass inversions were performed. The hyperspectral data of seaweed at different growth stages were analyzed, and it was found that the variation range was small (visible light range < 0.1). Through Principal Component Analysis (PCA), Most of the variance is explained in the first principal component, and the load allocated to the three kinds of seaweed is more than 90%. Through Pearson correlation analysis, 24 parameters of spectral features, 9 parameters of texture features (27 in total for the three RGB bands) and parameters of combined spectral and texture features of the images were selected for screening, and regression prediction was performed using two methods: Random Forest (RF), and Gradient Boosted Decision Tree (GBDT), combined with Pearson correlation coefficients. Compared with the other two models, GBDT has better fitting accuracy in the inversion of seaweed biomass, and the highest R2 was obtained when the top 17, 17 and 11 parameters with strong correlation were selected for the regression prediction by Pearson's correlation coefficient for Ulva australis, Sargassum thunbergii, and Sargassum fusiforme, and the R2 for Ulva australis was 0.784, RMSE 156.129, MAE 50.691 and MAPE 28.201, the R2 for Sargassum thunbergii was 0.854, RMSE 790.487, MAE 327.108 and MAPE 19.039, and the R2 for Sargassum fusiforme was 0.808, RMSE 445.067 and MAPE 28.822. MAE was 180.172 and MAPE was 28.822. The study combines in situ survey with machine learning methods, which has the advantages of being popular, efficient and environmentally friendly, and can provide technical support for intertidal seaweed surveys.
Subject(s)
Biomass , Ecosystem , Remote Sensing Technology , Seaweed/growth & development , Humans , Machine Learning , Principal Component Analysis , Tidal WavesABSTRACT
HLA class II molecules, HLA-DR, DP and DQ, together with HLA II-like protein DM, play a dominant role in the processing and presentation of antigens, which may influence vaccine effectiveness. We previously demonstrated that variations in the HLA-DRB1, DPB1 and DQB1 genes may affect the neutralising antibody (NAb) response induced by the inactivated Japanese encephalitis vaccine (IJEV). In the present study, we genotyped HLA-DPA1, DQA1, DMA and DMB genes and used previous HLA-DRB1, DPB1 and DQB1 data to evaluate the association of these genes with IJEV-induced NAbs, at both the seroconversion and geometric mean titres (GMTs). We confirmed the seropositive association of DQB1*02:01 and NAbs (0.156 vs. 0.075, p_adj = 0.018; OR = 2.270; 95% CI = 1.285-3.999) and seronegative association of DQB1*02:02 (0.014 vs. 0.09, p_adj = 0.0002; OR = 0.130; 95% CI = 0.047-0.400). Furthermore, the DMB*01:03-DMA*01:01-DPA1*01:03-DPB1*04:01 haplotype was associated with a negative response (0.020 vs. 0.074; p_adj = 0.03; OR = 0.250; 95% CI = 0.097-0.649), whereas DRB1*15:02-DMB*01:01-DMA*01:01 was associated with a positive response (0.034 vs. 0; p_adj = 0.044). In addition, DRB1*12:02, DRB1*13:02, DPB1*04:01, DPB1*05:01, DPB1*09:01, DQA1*06:01 and DQA1*01:02 were associated with a higher GMT of NAbs, whereas DRB1*11:01, DPB1*13:01 and DQA1*05:05 were associated with a lower GMT of NAbs. In conclusion, the present study suggests that variations in the HLA-DM and HLA class II genes, as well as their combined allotypes, may influence the IJEV NAbs at seroconversion and GMT levels.
Subject(s)
Genes, MHC Class II , Japanese Encephalitis Vaccines , Alleles , Antibody Formation , HLA-DRB1 Chains/genetics , HumansABSTRACT
Reducing the amount of antigen is an important strategy to resolve the present shortage of IPV supply for global polio eradication. In the study, we compared the immunogenicity of adjuvanted and non-adjuvanted fractional-dose of IPV made from Sabin strains (sIPV) by intradermal (ID) administration versus the full-dose of sIPV by intramuscular (IM) administration in rats by comparing seroconversion rates and geometric mean titers (GMTs) of neutralizing antibodies (NAbs). We found that, after the full 0, 1, 2 months schedule immunizations, the seroconversion rates in all groups reached 100% except non-adjuvanted 1/6 dose group. After 2 immunizations, the seroconversion rates in all the adjuvanted fractional-dose groups and the full-dose group reached 100%. The GMTs of NAbs induced by adjuvanted 1/12 fractional-dose and full-dose of sIPV were similar and dynamics of the antibody responses were consistent. We proves that the Th1/Th2 balance was not changed by the administration route by comparing ratios of the IgG subclass. Our study confirms that ID administration could reduce the required amount of antigens, the adjuvanted fractional-dose resulted in earlier and higher antibody response for all serotypes than that of non-adjuvanted fractional-dose, and the NAbs responses elicited by 1/12 dose was comparable to that by full-dose of sIPV.
Subject(s)
Poliomyelitis , Poliovirus , Animals , Antibodies, Viral , Immunogenicity, Vaccine , Poliomyelitis/prevention & control , Poliovirus Vaccine, Inactivated , Rats , Rats, Wistar , Vaccination/methodsABSTRACT
As one of the powerful vaccines for completely eradicating all types of poliovirus in the polio endgame period, the novel IPV, which is prepared from attenuated polio Sabin strains (sIPV) and is expected to reduce the overall biosafety risk, was licensed in Japan (sIPV-containing diphtheria-tetanus-acellular pertussis combination vaccines, DTP-sIPV) and China (sIPV) in November 2012 and January 2015, respectively. Limited by the development progress and the manufactured sIPV ability, it has to date only been used in Chinese Expanded Programme on Immunization (EPI) by sequential scheduling with bOPV and in Japan with DTP-sIPV vaccination. We herein summarize postapproval clinical studies of sIPV in both full-dose schedules and sequential schedules, focusing on China, to evaluate sIPV safety and immunogenicity in large populations to provide important data for its broad application in developing countries worldwide.
Subject(s)
Diphtheria-Tetanus-acellular Pertussis Vaccines , Poliomyelitis , Poliovirus , Antibodies, Viral , Diphtheria-Tetanus-Pertussis Vaccine , Humans , Immunization Schedule , Poliomyelitis/prevention & control , Poliovirus Vaccine, InactivatedABSTRACT
An ideal vaccine against SARS-CoV-2 is expected to elicit broad immunity to prevent viral infection and disease, with efficient viral clearance in the upper respiratory tract (URT). Here, the N protein and prefusion-full S protein (SFLmut) are combined with flagellin (KF) and cyclic GMP-AMP (cGAMP) to generate a candidate vaccine, and this vaccine elicits stronger systemic and mucosal humoral immunity than vaccines containing other forms of the S protein. Furthermore, the candidate vaccine administered via intranasal route can enhance local immune responses in the respiratory tract. Importantly, human ACE2 transgenic mice given the candidate vaccine are protected against lethal SARS-CoV-2 challenge, with superior protection in the URT compared with that in mice immunized with an inactivated vaccine. In summary, the developed vaccine can elicit a multifaceted immune response and induce robust viral clearance in the URT, which makes it a potential vaccine for preventing disease and infection of SARS-CoV-2.
Subject(s)
COVID-19 Vaccines/immunology , Combined Modality Therapy/methods , SARS-CoV-2/immunology , Adjuvants, Vaccine , Administration, Intranasal , Angiotensin-Converting Enzyme 2/immunology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Viral/immunology , Antigens/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/genetics , Chlorocebus aethiops , Coronavirus Nucleocapsid Proteins/immunology , Female , Flagellin/immunology , HEK293 Cells , Humans , Immunity/immunology , Immunity/physiology , Immunity, Humoral/immunology , Immunization , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Nucleotides, Cyclic/immunology , Phosphoproteins/immunology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/immunology , Vaccination , Vero CellsABSTRACT
Dose-sparing intradermal (ID) vaccination may induce the same immune responses as intramuscular (IM) vaccination, which can increase vaccine supplies and save costs. In this study, rats were immunized with fractional-dose of Sabin-derived IPV combined with diphtheria-tetanus-acellular pertussis vaccine (DTaP-sIPV) intradermally with hollow microneedle devices called MicronJet600 and the vaccine immunogenicity and efficacy were evaluated and compared with those of full-dose intramuscular immunization. We tested levels of antibodies and the subclass distribution achieved via different immunization routes. Furthermore, gene transcription in the lung and spleen, cytokine levels and protection against Bordetella pertussis (B. pertussis) infection were also examined. The humoral immune effect of DTaP-sIPV delivered with MicronJet600 revealed that this approach had a significant dose-sparing effect and induced more effective protection against B. pertussis infection by causing Th1/Th17 responses. In conclusion, ID immunization of DTaP-sIPV with the MicronJet600 is a better choice than IM immunization, and it has the potential to be a new DTaP-sIPV vaccination strategy.
ABSTRACT
Interferometric Rayleigh scattering technique is commonly employed to measure single-point velocity fluctuation and its standard deviation in a high-speed flow due to many benefits, such as high accuracy, easy data interpretation, and high sampling rate. However, this technique suffers from a severe problem often referred to as the weak Rayleigh scattering signal, especially in the supersonic and hypersonic flow with an extremely low gas molecule density. An asymmetry cavity structure that could cost-effectively improve the Rayleigh scattering (RS) signal of interest is designed and used in the interferemetric Rayleigh scattering technique. The ZEMAX simulations suggest that the parallel beam can be repeatedly reflected in the resonant cavity and can be focused in a measurement region with the order of 0.67â mm×1.31â mm. The number of propagating rays inside the cavity can reach about 50. The fidelity of this proposed cavity is then verified by the Rayleigh scattering imaging experiments. Results show that this cavity allows the laser beam to reflect several times in the resonant cavity, and the RS signal intensity in the major axis can be 10.4 times larger than that of the incident laser. The cavity is finally employed under realistic supersonic flow velocity measurements, where the results conclusively illustrate that the Rayleigh scattering signal of interest in a single direction can be improved by a factor of 4â¼5. In addition, the bi-directional (both the axial and radial directions) velocity parameters can also be obtained simultaneously. The axial velocity and its standard deviation are similar to conventional single-line ones.
ABSTRACT
BACKGROUND: The prevalent resurgence of pertussis has recently become a critical public health problem worldwide. To understand pertussis pathogenesis and the host response to both the pathogen and vaccines, a suitable pertussis animal model, particularly a non-human primate model, is necessary. Recently, a non-human primate pertussis model was successfully established with baboons. Rhesus macaques have been shown to be ideal animal models for several infectious diseases, but a model of infectious pertussis has not been established in these organisms. Studies on rhesus macaque models of pertussis were performed in the 1920s-1930s, but limited experimental details are available. Recent monkey pertussis models have not been successful because the typical clinical symptoms and transmission have not been achieved. METHODS: In the present study, infant rhesus macaques were challenged with Bordetella pertussis (B.p) using an aerosol method to evaluate the feasibility of this system as an animal model of pertussis. RESULTS: Upon aerosol infection, monkeys infected with the recently clinically isolated B.p strain 2016-CY-41 developed the typical whooping cough, leukocytosis, bacteria-positive nasopharyngeal wash (NPW), and interanimal transmission of pertussis. Both systemic and mucosal humoral responses were induced by B.p. CONCLUSION: These results demonstrate that a model of pertussis was successfully established in infant rhesus macaques. This model provides a valuable platform for research on pertussis pathogenesis and evaluation of vaccine candidates.
Subject(s)
Macaca mulatta , Whooping Cough/etiology , Whooping Cough/transmission , Aerosols/administration & dosage , Animals , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Bordetella pertussis/immunology , Bordetella pertussis/pathogenicity , Cytokines/blood , Disease Models, Animal , Leukocytosis/microbiology , Male , Nasopharynx/microbiologyABSTRACT
Although millions of patients have clinically recovered from COVID-19, little is known about the immune status of lymphocytes in these individuals. In this study, the peripheral blood mononuclear cells of a clinically recovered (CR) cohort were comparatively analyzed with those of an age- and sex-matched healthy donor cohort. We found that CD8+ T cells in the CR cohort had higher numbers of effector T cells and effector memory T cells but lower Tc1 (IFN-γ+), Tc2 (IL-4+), and Tc17 (IL-17A+) cell frequencies. The CD4+ T cells of the CR cohort were decreased in frequency, especially the central memory T cell subset. Moreover, CD4+ T cells in the CR cohort showed lower programmed cell death protein 1 (PD-1) expression and had lower frequencies of Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17A+), and circulating follicular helper T (CXCR5+PD-1+) cells. Accordingly, the proportion of isotype-switched memory B cells (IgM-CD20hi) among B cells in the CR cohort showed a significantly lower proportion, although the level of the activation marker CD71 was elevated. For CD3-HLA-DR- lymphocytes in the CR cohort, in addition to lower levels of IFN-γ, granzyme B and T-bet, the correlation between T-bet and IFN-γ was not observed. Additionally, by taking into account the number of days after discharge, all the phenotypes associated with reduced function did not show a tendency toward recovery within 4â11 weeks. The remarkable phenotypic alterations in lymphocytes in the CR cohort suggest that severe acute respiratory syndrome coronavirus 2 infection profoundly affects lymphocytes and potentially results in dysfunction even after clinical recovery.
Subject(s)
CD8-Positive T-Lymphocytes/virology , COVID-19/blood , Leukocytes, Mononuclear/virology , SARS-CoV-2/pathogenicity , Adult , Aged , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Cell Lineage/genetics , Cell Lineage/immunology , Female , Gene Expression Regulation/immunology , Granzymes/genetics , Humans , Interferon-gamma/genetics , Leukocytes, Mononuclear/pathology , Male , Middle Aged , T-Box Domain Proteins/genetics , Th1 Cells/immunology , Th1 Cells/virology , Th17 Cells/immunology , Th17 Cells/virology , Th2 Cells/immunology , Th2 Cells/virologyABSTRACT
OBJECTIVE: SARS-CoV-2 has caused a worldwide pandemic of COVID-19. The existence of prolonged SARS-CoV-2 positivity (PP) has further increased the burden on the health system. Since T cells are vital for viral control, we aimed to evaluate the characteristics of T-cell responses associated with PP. METHODS: We established a PP cohort and two age- and sex-matched control cohorts: a regular clinical recovery (CR) cohort and a healthy donor (HD) cohort. The mean time for RNA negativity conversion in the PP cohort was markedly longer than that in the CR cohort (66.2 vs 25.3 days), while the time from illness onset to sampling was not significantly different. T-cell responses in the PP cohort were assayed, analysed and compared with those in the CR and HD cohorts by flow cytometry and ELISpot analysis of peripheral blood mononuclear cells. RESULTS: Compared with the CR cohort, the proliferation, activation and functional potential of CD8+ and CD4+ T cells in the PP cohort were not significantly different. However, the frequencies and counts of Teff and Tem in CD8+ but not in CD4+ T cells of the PP cohort were prominently lower. Moreover, a weaker SARS-CoV-2 N protein-specific IFN-γ+ T-cell response and a higher frequency of Tregs were detected in the PP cohort. CONCLUSION: Suppressed CD8+ T-cell differentiation is associated with PP and may be an indicator for the prediction of prolonged SARS-CoV-2 positivity in COVID-19 patients. The association between suppressed CD8+ T-cell differentiation and elevated Tregs warrants studies in the future.
ABSTRACT
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.
ABSTRACT
As a recently launched novel vaccine used as one of the vaccines for the final eradication of polios worldwide, complete data on the consistency and immunogenicity characteristics of the inactivated poliomyelitis vaccine made from the Sabin strain (sIPV) and its safety in large-scale populations are required to support the future use of this vaccine worldwide. A phase IV clinical trial was conducted to perform an immunogenicity evaluation of lot-to-lot consistency of three commercial batches of sIPV in 1200 infants and to investigate the vaccine's safety on a large-scale in 20,019 infants for active monitoring and 29,683 infants for passive monitoring through the Adverse Event Following Immunization (AEFI) reporting system in China. In the immunogenicity evaluation, the average seroconversion rates for type I, type II and type III of the three groups were 99.83%, 98.93% and 99.44%, respectively. No differences in the seroconversion rate and the GMT ratios were noted in the pair-to-pair comparisons. In the large-scale safety evaluation, most adverse reactions occurred 0-30 days after the first doses, and the common local and systemic reactions were similar to those in the phase III clinical trial, with low incidence in both activated and passive monitoring. In conclusion, sIPV exhibits good lot-to-lot consistency and safety in large-scale populations; thus, it is qualified to serve as one of the vaccines for use in eradicating all wild and vaccine-derived polioviruses worldwide in the near future. Clinic Trial Registration. NCT04224519 and NCT04220515.
Subject(s)
Poliomyelitis , Poliovirus Vaccine, Oral , Antibodies, Viral , China , Humans , Immunogenicity, Vaccine , Infant , Poliomyelitis/prevention & control , Poliovirus Vaccine, Inactivated/adverse effects , Poliovirus Vaccine, Oral/adverse effects , VaccinationABSTRACT
This paper demonstrates that melt centrifugal spinning could be used to effectively fabricate degradable poly (butylene adipate-co-terephthalate) (PBAT) fibers with uniform fiber diameter. The hydrophobic PBAT fibers were modified into hydrophilic fibers using the hyperbranched polyesters (HBP) with three-dimensional molecular chain structures and a large number of functional groups at the chain ends. The structures and properties of the obtained fibers were characterized with SEM, XRD, DSC, contact angle, and tensile strength analyses. Results indicate that fibers with uniform diameters can be conveniently fabricated by designing a spinneret. The obtained fibers showed no apparent change in crystallization compared to PBAT pellets, while the thermal stability and mechanical properties of PBAT/HBP fibers were dependent on the HBP ratio in fibers. More importantly, the obtained fibers gradually changed from hydrophobic to super-hydrophilic with increasing HBP content in fibers up to 30%. The modified hydrophilic PBAT/HBP presents a greatly significant potential for application in biomedical fields.
ABSTRACT
The research and development of a pertussis-combined vaccine using a novel inactivated poliovirus vaccine made from the Sabin strain (sIPV) is of great significance in the polio eradication project and to address the recent resurge in pertussis. In the present study, we compared the immunogenicity and efficacy of a candidate DTacP-sIPV with those of a commercial DTacP-wIPV/Hib, DTaP/Hib, pertussis vaccine, and aluminum hydroxide adjuvant control in the rhesus macaque model with a 0-, 1-, and 2-month immunization schedule. At day 28 after the third dose, rhesus macaques were challenged with aerosol pertussis and the antibody and cellular response together with pertussis clinical symptoms were determined. The production of anti-PT, anti-PRN, anti-FHA, anti-DT, anti-TT, and polio type I, II, III antibodies was induced by the candidate DTacP-sIPV, which was as potent as commercial vaccines. In comparison with the control group that showed typical pertussis symptoms of humans after the aerosol challenge, the DTacP-sIPV group did not exhibit obvious clinical pertussis symptoms and had higher neutralization titers of anti-PT, anti-PRN, and anti-FHA. In conclusion, the DTacP-sIPV vaccine was able to induce immunity in rhesus macaques to prevent pertussis infections after immunization. The developed vaccine was as efficient as other commercial vaccines.
ABSTRACT
With more demand for Sabin inactivated poliovirus vaccines (sIPVs) to support the global polio eradication effort worldwide, data regarding the potency characteristics of sIPV after exposure to freezing temperatures are urgently required. In the present study, the sIPVs were stored at -20°C for 24 h, 1 week, and 2 weeks in the freezer or in a vaccine carrier for 1 or 3 freeze-thaw cycle to evaluate the effect mediated by freezing temperatures that may be encountered during routine storage and transfer. The in vitro potency was then determined by a D-antigen enzyme-linked immunosorbent assay, and the in vivo potency was evaluated in Wistar rats. In the in vitro study for freezer storage groups, the D-antigen contents for all three types decreased and were lower than the release specifications after storing at -20°C for 2 weeks. After storing at -20°C for 1 week, the D-antigen contents for types I and III in combined group of a total of 45 vials, and for type II in the specific lot groups containing 15 vials decreased, but were within the release specifications. Moreover, no significant change in in vivo potency was observed. For vaccine carrier transfer groups, the D-antigen contents did not decrease after 1 freeze-thaw cycle; in contrast, it decreased, but no significant in vivo potency loss was observed after 3 freeze-thaw cycles. These results suggest that it may be possible to retain sufficient sIPV potency after short periods of freezing or freeze-thawing during transport.