Avian metapneumovirus(aMPV) is a highly contagious pathogen that causes acute upper respiratory tract diseases in chickens and turkeys, resulting in serious economic losses. Subtype B aMPV has recently become the domi...Avian metapneumovirus(aMPV) is a highly contagious pathogen that causes acute upper respiratory tract diseases in chickens and turkeys, resulting in serious economic losses. Subtype B aMPV has recently become the dominant epidemic strain in China. We developed an attenuated aMPV subtype B strain by serial passaging in Vero cells and evaluated its safety and efficacy as a vaccine candidate. The safety test showed that after the 30th passage, the LN16-A strain was fully attenuated, as clinical signs of infection and histological lesions were absent after inoculation.The LN16-A strain did not revert to a virulent strain after five serial passages in chickens. The genomic sequence of LN16-A differed from that of the parent wild-type LN16(wtLN16) strain and had nine amino acid mutations. In chickens, a single immunization with LN16-A induced robust humoral and cellular immune responses, including the abundant production of neutralizing antibodies, CD4^(+) T lymphocytes, and the Th1(IFN-γ) and Th2(IL-4 and IL-6)cytokines. We also confirmed that LN16-A provided 100% protection against subtype B aMPV and significantly reduced viral shedding and turbinate inflammation. Our findings suggest that the LN16-A strain is a promising live attenuated vaccine candidate that can prevent infection with subtype B aMPV.展开更多
Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the sci...Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.展开更多
This study undertakes a thorough analysis of the sentiment within the r/Corona-virus subreddit community regarding COVID-19 vaccines on Reddit. We meticulously collected and processed 34,768 comments, spanning from No...This study undertakes a thorough analysis of the sentiment within the r/Corona-virus subreddit community regarding COVID-19 vaccines on Reddit. We meticulously collected and processed 34,768 comments, spanning from November 20, 2020, to January 17, 2021, using sentiment calculation methods such as TextBlob and Twitter-RoBERTa-Base-sentiment to categorize comments into positive, negative, or neutral sentiments. The methodology involved the use of Count Vectorizer as a vectorization technique and the implementation of advanced ensemble algorithms like XGBoost and Random Forest, achieving an accuracy of approximately 80%. Furthermore, through the Dirichlet latent allocation, we identified 23 distinct reasons for vaccine distrust among negative comments. These findings are crucial for understanding the community’s attitudes towards vaccination and can guide targeted public health messaging. Our study not only provides insights into public opinion during a critical health crisis, but also demonstrates the effectiveness of combining natural language processing tools and ensemble algorithms in sentiment analysis.展开更多
Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature...Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature research,case study and comparative study were used to analyze the quality management system of clinical trials of therapeutic vaccines.Results and Conclusion From the perspective of the sponsor,investigators and the thirdparty technical service company,the problems such as the low efficiency of clinical trial sample preparation and the lax implementation of the protocol by hospital departments in the quality management of clinical trials of therapeutic vaccines in China were found.Then,the optimization plan for the quality management of clinical trials of therapeutic vaccines is proposed,including optimizing the preparation process of therapeutic vaccines and strengthening the training of hospital department personnel.展开更多
Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoi...Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoid(TT)as bivalent conjugates.Methods:Different molecular weights(MWs)of polysaccharides,activating agents and capsular polysaccharide/protein(CP/Pro)ratio that may influence conjugation and immunogenicity were investigated and optimized to prepare the bivalent conjugate bulk.Using the described method and optimized parameters,a 20-valent pneumococcal conjugate vaccine and a bivalent meningococcal vaccine were developed and their effectiveness was compared to that of corresponding licensed vaccines in rabbit or mouse models.Results:The immunogenicity test revealed that polysaccharides with lower MWs were better for Pn1-TT-Pn3 and MenA-TT-MenC,while higher MWs were superior for Pn4-TT-Pn14,Pn6A-TT-Pn6B,Pn7F-TT-Pn23F and Pn8-TT-Pn11A.For activating polysaccharides,1-cyano-4-dimethylaminopyridinium tetrafluoroborate(CDAP)was superior to cyanogen bromide(CNBr),but for Pn1,Pn3 and MenC,N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride(EDAC)was the most suitable option.For Pn6A-TT-Pn6B and Pn8-TT-Pn11A,rabbits immunized with bivalent conjugates with lower CP/Pro ratios showed significantly stronger CP-specific antibody responses,while for Pn4-TT-Pn14,higher CP/Pro ratio was better.Instead of interfering with the respective immunological activity,our bivalent conjugates usually induced higher IgG titers than their monovalent counterparts.Conclusion:The result indicated that the described conjugation technique was feasible and efficacious to prepare glycoconjugate vaccines,laying a solid foundation for developing extended-valent multivalent or combined conjugate vaccines without potentially decreased immune function.展开更多
Objective:To investigate the importance of immunization in preventing measles infection and to determine the most useful laboratory tests for confirmation of measles.Methods:This study included pediatric cases evaluat...Objective:To investigate the importance of immunization in preventing measles infection and to determine the most useful laboratory tests for confirmation of measles.Methods:This study included pediatric cases evaluated with a presumed diagnosis of measles between December 2022 and June 2023,at Marmara University Pendik Training and Research Hospital.The effects of vaccination status and underlying disease on the clinical course,treatments,and complications were evaluated.Results:In total,117 patients were enrolled in the study with a median age of 80 months(IQR:32.5-125.0).Twelve patients with contact history were asymptomatic and had an underlying disorder,and intravenous immunoglobulin was given to them for post-exposure prophylaxis.Fifty-one patients had confirmed measles diagnosis.Ribavirin treatment was given to three patients(a newborn,a girl with rhabdomyosarcoma,and a healthy boy)with respiratory distress.Seventy-eight percent of confirmed measles cases were unvaccinated,and all hospitalized cases were unvaccinated or under-vaccinated.Four full-vaccinated children had confirmed measles infection.Measles PCR from nasopharyngeal swabs was negative in all of them,and their diagnosis was established with anti-measles IgM positivity.Conclusions:The measles vaccine is the most effective way to protect from measles and measles-related complications.Although measles can also occur in fully vaccinated patients,the disease is milder than in unvaccinated patients.Using ELISA and RT-PCR tests together may be beneficial in patients with high clinical suspicion for early diagnosis.展开更多
Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resist...Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise treatment.Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological memory.Multiple conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains unsatisfactory.Compared with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer.This review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.展开更多
BACKGROUND Vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which were approved for emergency use have been administered on a large scale globally to contain the pandemic coronavirus disease...BACKGROUND Vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which were approved for emergency use have been administered on a large scale globally to contain the pandemic coronavirus disease 2019(COVID-19)and to save lives.Vaccine safety is one of the issues under surveillance and a possible correlation between vaccines and thyroid function has been reported.However,reports of the impact of coronavirus vaccines on those with Graves’disease(GD)are rare.CASE SUMMARY This paper presents two patients with underlying GD in remission,both developed thyrotoxicosis and one developed thyroid storm following the adenovirus-vectored vaccine(Oxford-AstraZeneca,United Kingdom).The objective of this article is to raise awareness regarding a possible association between COVID-19 vaccination and the onset of thyroid dysfunction in patients with underlying GD in remission.CONCLUSION Receiving either the mRNA or an adenovirus-vectored vaccine for SARS-CoV-2could be safe under effective treatment.Vaccine induced thyroid dysfunction has been reported,but the pathophysiology still not well understood.Further investigation is required to evaluate the possible predisposing factors for developing thyrotoxicosis especially in patients with underlying GD.However,early awareness of thyroid dysfunction following vaccination could avoid a lifethreatening event.展开更多
Last time the world faced a deadly pandemic was the H1N1 Spanish flu in 1918, which affected almost one third of the world’s population (500 million people). Since then, almost 100 years later, we are now facing anot...Last time the world faced a deadly pandemic was the H1N1 Spanish flu in 1918, which affected almost one third of the world’s population (500 million people). Since then, almost 100 years later, we are now facing another pandemic of the SARS-CoV2 virus (Covid-19), which is still endemic to this day. As technology evolved during those 100 years, an effective vaccine for Covid-19 was produced within only a year, a huge feat. But, unfortunately, due to its fast development, another force would arise limiting the impact of the vaccine: Vacccine hesitancy and anti-vaxxers, which John Hopkins and the World Health Organization call the biggest current threat to global health. From politics to social media, it is clear that there has been a rapid spread of misinformation, resulting in hesitancy, especially from sociopolitically motivated people popularly referred to as antivaccers. However, a second group of vaccine-hesitant people have also emerged, who are uneducated and remain undecided about vaccination mostly due to safety concerns. They come under the massive influence of anti-vaxxers and anti-vaccine propaganda through social media and politicians, which often make bold claims and huge headlines. To combat vaccine hesitancy, it is crucial that we debunk these conspiracy theories and misinformation that so many believe in, with factual, data-based information. Actively spreading correct information about the vaccines, such as disclosing the rigorous developmental processes and validation of safety data by the FDA, assurance for unlikeliness of getting a lethal side effect along with tremendous health benefits, will encourage people to safe vaccination against Covid-19 and other potentially infectious diseases in future. This article discusses the role of anti-vaxxers and vaccine hesitancy groups, electronic social media, and politics in vaccine hesitancy among people. It describes the strategies to combat the roadblocks in the vaccination programs and health benefits, offered by recent advances in scientific and technological developments.展开更多
Background: HPV vaccines were introduced globally as one of the most effective strategies to prevent cervical cancer. HPV vaccines were rolled out in Kenya in 2019 targeting girls aged 10 - 14 years, but the uptake ha...Background: HPV vaccines were introduced globally as one of the most effective strategies to prevent cervical cancer. HPV vaccines were rolled out in Kenya in 2019 targeting girls aged 10 - 14 years, but the uptake has not been satisfactory. The Purpose of the Study: The aim of the study was to assess the level of HPV uptake among girls aged 10 - 14 years in Rongai and Nakuru West Sub-Counties in Nakuru County. Method: This was a cross-sectional study where data on HPV uptake was retrieved from all the public health facilities located in Rongai and Nakuru West Sub-Counties, Nakuru County, entered into Microsoft Excel then transferred to SPSS version 26 for analysis of HPV vaccine uptake since the year 2019 to June 2022. Data Analysis: Descriptive statistics were used where tables and graphs were generated to represent the percentages and trends of HPV vaccine uptake. Results: The average percentage of HPV uptake in Nakuru West Sub-County since the rollout of vaccination was 17% while that of Rongai Sub-County was 15%. In 2019, HPV 1 uptake was generally low for both Sub-Counties, the results show no HPV 2 vaccines were administered during that year. In 2020, Nakuru West reported an increase in HPV 1 uptake, while Rongai reported a drop in HPV 1 uptake. Both Sub-Counties reported an increase in HPV 2 in 2020 as compared to the previous year. The highest HPV 1 & 2 uptakes were reported in 2021 in both Sub-Counties. The uptake of both HPV 1 & 2 kept increasing subsequently. Conclusion: The overall uptake of HPV vaccines for Doses 1 and 2, in both Rongai and Nakuru West Sub-Counties, is low. However, there has been a consistent increase in uptake of the two doses in the two Sub-Counties since 2019. Therefore, raising public awareness of the importance of HPV vaccination could improve uptake.展开更多
Although the coronavirus disease 2019(COVID-19)pandemic was declared to be no longer“a public health emergency of international concern”with its wide range of clinical manifestations and late complications,severe ac...Although the coronavirus disease 2019(COVID-19)pandemic was declared to be no longer“a public health emergency of international concern”with its wide range of clinical manifestations and late complications,severe acute respiratory syndrome coronavirus 2 infection proved to be a serious threat,especially to the elderly and patients with comorbidities.Patients with oncologic diseases are vulnerable to severe infection and death.Indeed,patients with oncohematological diseases have a higher risk of severe COVID-19 and impaired post-vaccination immunity.Unfortunately,cancer patients are usually excluded from vaccine trials and investigations of post-vaccinal immune responses and the effectiveness of the vaccines.We aimed to elucidate to what extent patients with cancer are at increased risk of developing severe COVID-19 and what is their overall case fatality rate.We also present the current concept and evidence on the effectiveness and safety of COVID-19 vaccines,including boosters,in oncology patients.In conclusion,despite the considerably higher mortality in the cancer patient group than the general population,countries with high vaccination rates have demonstrated trends toward improved survival of cancer patients early and late in the pandemic.展开更多
This study aimed to examine the relationship between COVID-19 vaccine refusal and religiosity and fear of death among Muslims living in Turkey. This cross-sectional study was conducted online with 1046 adults aged 18 ...This study aimed to examine the relationship between COVID-19 vaccine refusal and religiosity and fear of death among Muslims living in Turkey. This cross-sectional study was conducted online with 1046 adults aged 18 and older. The Ok-Religious Attitude Scale (Islam) (ORASI) (8 items) and Thorson-Powell Death Anxiety Scale (TPDAS) (20 items) were used as data collection instruments. The data were analyzed using the Pearson chi-square test, Student’s t-test, and binary logistic regression. A p-value of 0.05). In binary logistic regression analysis, vaccine rejection was 7.19 times higher among single people, 50.55 times higher among workers and tradesmen, and 3.36 times higher among people who did not have COVID-19. As religiosity increased, the risk of vaccine refusal decreased 1.037-fold.展开更多
The technology behind vaccine development varies significantly from one vaccine to another depending on the time when the vaccine was first developed. Over the years, the vaccine innovation time has significantly shor...The technology behind vaccine development varies significantly from one vaccine to another depending on the time when the vaccine was first developed. Over the years, the vaccine innovation time has significantly shortened with the advancement of knowledge in the fields of molecular and cell biology, and discoveries in the field of biotechnology. The first vaccines created were tested in a kind of trial-and-error approach which sometimes had deadly side effects. These vaccines used either living, weakened, or completely dead pathogens. The use of whole pathogen vaccines was seen to be time consuming and unpredictable because even though it would cause an immune response, it could vary from person to person, and always had the risk of pathogens returning to virulence causing sometimes fatal outcomes. The next major technology used to create vaccines was subunit vaccines which utilize purified antigens inactivated through various methods. This technology is quite prevalent among the vaccines that are currently in circulation, making them quite effective, and free from fatal side effects. The viral vector vaccine technology has been around for a few decades and utilizes knowledge of molecular genetics to the greatest extent. It uses intermediate vectors to deliver genetic instructions to trigger an immune response within the subject body. The introduction of nucleic acid vaccines is the newest technology and has come to a great deal of attention during the SARS-CoV-2 immunization efforts. The technology primarily utilizes the delivery of genetic information using messenger ribonucleic acid (mRNA) to create characteristic pathogen-specific proteins that in turn generate an immune response in the recipients.展开更多
Malignant tumors are still a worldwide threat to human health.Tumor treatment strategies are constantly evolving,and the advent of tumor immunotherapy has brought up hope to many types of tumors,especially for those t...Malignant tumors are still a worldwide threat to human health.Tumor treatment strategies are constantly evolving,and the advent of tumor immunotherapy has brought up hope to many types of tumors,especially for those that are refractory to conventional therapies including surgery,radiotherapy,and chemotherapy.Tumor vaccines can initiate or amplify an anti-tumor immune response in tumor patients through active immunization,and therefore occupy an important position in tumor immunotherapy.The main types of tumor vaccines include tumor cell vaccines,dendritic cell vaccines,polypeptide vaccines and nucleic acid vaccines.Due to factors such as poor antigen selection and suppressive tumor microenvironment,earliest tumor vaccines on clinical trials failed to achieve satisfactory clinical effects.However,with the development of second-generation genome sequencing technologies and bioinformatics tools,it is possible to predict neoantigens generated by tumor-specific mutations and therefore prepare personalized vaccines.This article summarizes the global efforts in developing tumor vaccines and highlights several representative tumor vaccines in each category.展开更多
Objective:To examine COVID-19 vaccine uptake and its determinants among teenagers and their parents in Zhejiang,China.Methods:An online cross-sectional study was conducted among parents of teenagers in Zhejiang,China ...Objective:To examine COVID-19 vaccine uptake and its determinants among teenagers and their parents in Zhejiang,China.Methods:An online cross-sectional study was conducted among parents of teenagers in Zhejiang,China from May 1 to 31,2022.Data were interpreted via univariate and multivariate analyses using the statistical package for the social sciences(SPSS)program.Results:A total of 11115(96.11%)participants and 11449(99.00%)of their children in Zhejiang,China had been vaccinated against COVID-19.Children whose parents did not receive COVID-19 vaccination were 19 times(aOR 18.96,95%CI 12.36-29.08)more likely to be unvaccinated than their counterparts.In addition,children with no previous influenza vaccination,those whose parents doubted the COVID-19 vaccine’s safety or effectiveness,were 6.11 times(aOR 6.11,95%CI 2.80-13.34),8.27 times(aOR 8.27,95%CI 5.33-12.83),and 2.69 times(aOR 2.69,95%CI 1.11-6.50)more likely to be unvaccinated than their counterparts,respectively.COVID-19 vaccine uptake varied between different sociodemographic groups.However,the odds of receiving the COVID-19 vaccine decreased as age and education level increased.The main refusal reasons claimed by participants were that they had medical conditions that may not qualify them for vaccination(53.78%),followed by safety concerns about the vaccine(13.56%),not knowing where to get vaccinated(6.44%),and concerns about fertility issues(5.56%).Conclusions:Despite a highly encouraging level of COVID-19 vaccine uptake in Zhejiang,China,the elderly and highly educated people had lower COVID-19 vaccine uptake.It is suggested that tailored health education strategies should be taken to increase the COVID-19 vaccine uptake in such groups.Furthermore,with vaccination rates at such a high level,the pandemic is still ongoing,and public confidence in vaccines may decline.Thus,sufficient evidence-based information regarding COVID-19 vaccines should be provided to the public.展开更多
Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunot...Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunotherapeutic strategy has attracted much attention for various diseases,however,its application in CHOL is limited due to the thoughtlessness in the integration of vaccine design and patient selection.A recent study established an integrated path for identifying potent CHOL antigens for mRNA vaccine development and a precise stratification for identifying CHOL patients who can benefit from the mRNA vaccines.In spite of a promising prospect,further investigations should identify immunogenic antigens and onco-immunological characteristics of CHOL to guide the clinical application of CHOL mRNA vaccines in the future.展开更多
Aeromonas hydrophila is a Gram-negative pathogen that can infect various fish,including largemouth bass(Micropterus salmoides),which have caused huge economic losses.In present study,largemouth bass anti-A.hydrophila ...Aeromonas hydrophila is a Gram-negative pathogen that can infect various fish,including largemouth bass(Micropterus salmoides),which have caused huge economic losses.In present study,largemouth bass anti-A.hydrophila antibodies were produced,then a highly immunogenic outer membrane proteins,AHA_3793,was identified by combined western blotting and mass spectrometry analysis.Moreover,AHA_3793 was expressed,and its immunogenicity was further verified by western blotting.Subsequently,the protective efficacy of AHA_3793 were evaluated in largemouth bass.The results showed that rAHA_3793 could produce a relative percentage survival(RPS)of 61.76% for largemouth bass against A.hydrophila challenge.ELISA analysis showed the specific serum antibodies of largemouth bass against rAHA_3793 and A.hydrophila in vaccinated group in weeks 4 and 5 after immunization were significantly higher than those in control group,which suggested that rAHA_3793 induced production of specific serum antibodies against rAHA_3793 and A.hydrophila.The qRT-PCR analysis showed that expressions of CD4-2 and MHC Ⅱα were also significantly up-regulated after immunization.These results collectively demonstrated that rAHA_3793 could induce a strong humoral immune response of largemouth bass,and then produce high immune protection ef fects against A.hydrophila infection.展开更多
Vibrio scophthalmi and Aeromonas salmonicida can cause high turbot mortality and huge economic losses.Presently,vaccination is the most promising method for preventing communicable diseases.In this study,we used forma...Vibrio scophthalmi and Aeromonas salmonicida can cause high turbot mortality and huge economic losses.Presently,vaccination is the most promising method for preventing communicable diseases.In this study,we used formalin to kill V.scophthalmi and A.salmonicida cells,and mixed with the mineralized oil adjuvant(Montanide^(TM)ISA 763 AVG)to prepare the bivalent inactivated vaccine.The results showed that turbot inoculated with the bivalent inactivated vaccine exhibited strong tolerance to the infection of V.scophthalmi and A.salmonicida,and no obvious clinical symptoms and pathological changes were observed.The activities of enzymes lysozyme,acid phosphatase and complement C3 had significantly increased after the vaccination.The antibody titer response of vaccinated turbot was greatly boosted,which was positively connected with the immunological impact according to ELISA results.Simultaneously,the expression levels of immune-related genes such as MHC-IIα,MHC-IIβ,CD4,CD8,TNF-αand IL^(-1)βwere up-regulated,demonstrating that it might stimulate humoral and cellular immunological response in turbot.These findings highlight the potential of the bivalent inactivated vaccine for controlling V.scophthalmi and A.salmonicida infections in turbot.展开更多
Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents...Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4t and CD8t T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.展开更多
Objective:To assess the knowledge of healthcare workers on the measles vaccine and its cold chain management.Method:An institutional-based cross-sectional study was conducted from February 1 to March 30,2022 in Gondar...Objective:To assess the knowledge of healthcare workers on the measles vaccine and its cold chain management.Method:An institutional-based cross-sectional study was conducted from February 1 to March 30,2022 in Gondar City Administration public health institutions among 165 healthcare workers.Data were collected using a structured questionnaire.In addition,an on-spot observation checklist was used to assess the availability,status and management of the cold chain.A logistic regression model was used to assess the relationship between the outcome and predictor variables.Crude and adjusted odds ratios were calculated with 95%confidence intervals.Results:Overall,87(52.7%;95%CI 44.8%-60.5%)of the healthcare workers had unsatisfactory knowledge regarding the measles vaccine and its cold chain management.One hundred thirty-six(82.4%)healthcare workers correctly mentioned the recommended range of temperature(2-8℃)for measles vaccine storage.Healthcare workers aged 18-29 years(P=0.001)and 30-44 years(P=0.014)were observed as determinants of unsatisfactory knowledge on the measles vaccine and its cold chain management.One hundred and five(63.6%)of the healthcare workers did not correctly mention the type of measles vaccine used in routine immunization.More than one-third(36.4%)of the healthcare workers perceived that the measles vaccine is not safe and could cause measles.Conclusions:More than half of the healthcare workers in the study area had unsatisfactory knowledge on the measles vaccine and its cold chain management.It is necessary to provide technical support and in-service training for healthcare workers to ensure optimal immunization effectiveness.展开更多
基金supported by the National Key Research and Development Program of China (2022YFD1800604)the China Agricultural Research System (CARS-41)the Heilongjiang Touyan Innovation Team Program of China
文摘Avian metapneumovirus(aMPV) is a highly contagious pathogen that causes acute upper respiratory tract diseases in chickens and turkeys, resulting in serious economic losses. Subtype B aMPV has recently become the dominant epidemic strain in China. We developed an attenuated aMPV subtype B strain by serial passaging in Vero cells and evaluated its safety and efficacy as a vaccine candidate. The safety test showed that after the 30th passage, the LN16-A strain was fully attenuated, as clinical signs of infection and histological lesions were absent after inoculation.The LN16-A strain did not revert to a virulent strain after five serial passages in chickens. The genomic sequence of LN16-A differed from that of the parent wild-type LN16(wtLN16) strain and had nine amino acid mutations. In chickens, a single immunization with LN16-A induced robust humoral and cellular immune responses, including the abundant production of neutralizing antibodies, CD4^(+) T lymphocytes, and the Th1(IFN-γ) and Th2(IL-4 and IL-6)cytokines. We also confirmed that LN16-A provided 100% protection against subtype B aMPV and significantly reduced viral shedding and turbinate inflammation. Our findings suggest that the LN16-A strain is a promising live attenuated vaccine candidate that can prevent infection with subtype B aMPV.
基金This work is supported by the United Arab Emirates University UPAR(Grant No.G3458).
文摘Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.
文摘This study undertakes a thorough analysis of the sentiment within the r/Corona-virus subreddit community regarding COVID-19 vaccines on Reddit. We meticulously collected and processed 34,768 comments, spanning from November 20, 2020, to January 17, 2021, using sentiment calculation methods such as TextBlob and Twitter-RoBERTa-Base-sentiment to categorize comments into positive, negative, or neutral sentiments. The methodology involved the use of Count Vectorizer as a vectorization technique and the implementation of advanced ensemble algorithms like XGBoost and Random Forest, achieving an accuracy of approximately 80%. Furthermore, through the Dirichlet latent allocation, we identified 23 distinct reasons for vaccine distrust among negative comments. These findings are crucial for understanding the community’s attitudes towards vaccination and can guide targeted public health messaging. Our study not only provides insights into public opinion during a critical health crisis, but also demonstrates the effectiveness of combining natural language processing tools and ensemble algorithms in sentiment analysis.
文摘Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature research,case study and comparative study were used to analyze the quality management system of clinical trials of therapeutic vaccines.Results and Conclusion From the perspective of the sponsor,investigators and the thirdparty technical service company,the problems such as the low efficiency of clinical trial sample preparation and the lax implementation of the protocol by hospital departments in the quality management of clinical trials of therapeutic vaccines in China were found.Then,the optimization plan for the quality management of clinical trials of therapeutic vaccines is proposed,including optimizing the preparation process of therapeutic vaccines and strengthening the training of hospital department personnel.
文摘Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoid(TT)as bivalent conjugates.Methods:Different molecular weights(MWs)of polysaccharides,activating agents and capsular polysaccharide/protein(CP/Pro)ratio that may influence conjugation and immunogenicity were investigated and optimized to prepare the bivalent conjugate bulk.Using the described method and optimized parameters,a 20-valent pneumococcal conjugate vaccine and a bivalent meningococcal vaccine were developed and their effectiveness was compared to that of corresponding licensed vaccines in rabbit or mouse models.Results:The immunogenicity test revealed that polysaccharides with lower MWs were better for Pn1-TT-Pn3 and MenA-TT-MenC,while higher MWs were superior for Pn4-TT-Pn14,Pn6A-TT-Pn6B,Pn7F-TT-Pn23F and Pn8-TT-Pn11A.For activating polysaccharides,1-cyano-4-dimethylaminopyridinium tetrafluoroborate(CDAP)was superior to cyanogen bromide(CNBr),but for Pn1,Pn3 and MenC,N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride(EDAC)was the most suitable option.For Pn6A-TT-Pn6B and Pn8-TT-Pn11A,rabbits immunized with bivalent conjugates with lower CP/Pro ratios showed significantly stronger CP-specific antibody responses,while for Pn4-TT-Pn14,higher CP/Pro ratio was better.Instead of interfering with the respective immunological activity,our bivalent conjugates usually induced higher IgG titers than their monovalent counterparts.Conclusion:The result indicated that the described conjugation technique was feasible and efficacious to prepare glycoconjugate vaccines,laying a solid foundation for developing extended-valent multivalent or combined conjugate vaccines without potentially decreased immune function.
文摘Objective:To investigate the importance of immunization in preventing measles infection and to determine the most useful laboratory tests for confirmation of measles.Methods:This study included pediatric cases evaluated with a presumed diagnosis of measles between December 2022 and June 2023,at Marmara University Pendik Training and Research Hospital.The effects of vaccination status and underlying disease on the clinical course,treatments,and complications were evaluated.Results:In total,117 patients were enrolled in the study with a median age of 80 months(IQR:32.5-125.0).Twelve patients with contact history were asymptomatic and had an underlying disorder,and intravenous immunoglobulin was given to them for post-exposure prophylaxis.Fifty-one patients had confirmed measles diagnosis.Ribavirin treatment was given to three patients(a newborn,a girl with rhabdomyosarcoma,and a healthy boy)with respiratory distress.Seventy-eight percent of confirmed measles cases were unvaccinated,and all hospitalized cases were unvaccinated or under-vaccinated.Four full-vaccinated children had confirmed measles infection.Measles PCR from nasopharyngeal swabs was negative in all of them,and their diagnosis was established with anti-measles IgM positivity.Conclusions:The measles vaccine is the most effective way to protect from measles and measles-related complications.Although measles can also occur in fully vaccinated patients,the disease is milder than in unvaccinated patients.Using ELISA and RT-PCR tests together may be beneficial in patients with high clinical suspicion for early diagnosis.
基金supported by the National Natural Science Foundation of China (31970696, 81502975, 82188102, and 81830089)Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar (LR22H160010)+2 种基金National Key Research and Development Program of China (2019YFC1316000)Zhejiang Provincial Key Research and Development Program (2019C03019)Zhejiang Provincial College Student Science and Technology Innovation Activity Plan-College Student Innovation and Entrepreneurship Incubation Program (Young Talent Program)(2022R40122)
文摘Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise treatment.Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological memory.Multiple conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains unsatisfactory.Compared with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer.This review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.
文摘BACKGROUND Vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which were approved for emergency use have been administered on a large scale globally to contain the pandemic coronavirus disease 2019(COVID-19)and to save lives.Vaccine safety is one of the issues under surveillance and a possible correlation between vaccines and thyroid function has been reported.However,reports of the impact of coronavirus vaccines on those with Graves’disease(GD)are rare.CASE SUMMARY This paper presents two patients with underlying GD in remission,both developed thyrotoxicosis and one developed thyroid storm following the adenovirus-vectored vaccine(Oxford-AstraZeneca,United Kingdom).The objective of this article is to raise awareness regarding a possible association between COVID-19 vaccination and the onset of thyroid dysfunction in patients with underlying GD in remission.CONCLUSION Receiving either the mRNA or an adenovirus-vectored vaccine for SARS-CoV-2could be safe under effective treatment.Vaccine induced thyroid dysfunction has been reported,but the pathophysiology still not well understood.Further investigation is required to evaluate the possible predisposing factors for developing thyrotoxicosis especially in patients with underlying GD.However,early awareness of thyroid dysfunction following vaccination could avoid a lifethreatening event.
文摘Last time the world faced a deadly pandemic was the H1N1 Spanish flu in 1918, which affected almost one third of the world’s population (500 million people). Since then, almost 100 years later, we are now facing another pandemic of the SARS-CoV2 virus (Covid-19), which is still endemic to this day. As technology evolved during those 100 years, an effective vaccine for Covid-19 was produced within only a year, a huge feat. But, unfortunately, due to its fast development, another force would arise limiting the impact of the vaccine: Vacccine hesitancy and anti-vaxxers, which John Hopkins and the World Health Organization call the biggest current threat to global health. From politics to social media, it is clear that there has been a rapid spread of misinformation, resulting in hesitancy, especially from sociopolitically motivated people popularly referred to as antivaccers. However, a second group of vaccine-hesitant people have also emerged, who are uneducated and remain undecided about vaccination mostly due to safety concerns. They come under the massive influence of anti-vaxxers and anti-vaccine propaganda through social media and politicians, which often make bold claims and huge headlines. To combat vaccine hesitancy, it is crucial that we debunk these conspiracy theories and misinformation that so many believe in, with factual, data-based information. Actively spreading correct information about the vaccines, such as disclosing the rigorous developmental processes and validation of safety data by the FDA, assurance for unlikeliness of getting a lethal side effect along with tremendous health benefits, will encourage people to safe vaccination against Covid-19 and other potentially infectious diseases in future. This article discusses the role of anti-vaxxers and vaccine hesitancy groups, electronic social media, and politics in vaccine hesitancy among people. It describes the strategies to combat the roadblocks in the vaccination programs and health benefits, offered by recent advances in scientific and technological developments.
文摘Background: HPV vaccines were introduced globally as one of the most effective strategies to prevent cervical cancer. HPV vaccines were rolled out in Kenya in 2019 targeting girls aged 10 - 14 years, but the uptake has not been satisfactory. The Purpose of the Study: The aim of the study was to assess the level of HPV uptake among girls aged 10 - 14 years in Rongai and Nakuru West Sub-Counties in Nakuru County. Method: This was a cross-sectional study where data on HPV uptake was retrieved from all the public health facilities located in Rongai and Nakuru West Sub-Counties, Nakuru County, entered into Microsoft Excel then transferred to SPSS version 26 for analysis of HPV vaccine uptake since the year 2019 to June 2022. Data Analysis: Descriptive statistics were used where tables and graphs were generated to represent the percentages and trends of HPV vaccine uptake. Results: The average percentage of HPV uptake in Nakuru West Sub-County since the rollout of vaccination was 17% while that of Rongai Sub-County was 15%. In 2019, HPV 1 uptake was generally low for both Sub-Counties, the results show no HPV 2 vaccines were administered during that year. In 2020, Nakuru West reported an increase in HPV 1 uptake, while Rongai reported a drop in HPV 1 uptake. Both Sub-Counties reported an increase in HPV 2 in 2020 as compared to the previous year. The highest HPV 1 & 2 uptakes were reported in 2021 in both Sub-Counties. The uptake of both HPV 1 & 2 kept increasing subsequently. Conclusion: The overall uptake of HPV vaccines for Doses 1 and 2, in both Rongai and Nakuru West Sub-Counties, is low. However, there has been a consistent increase in uptake of the two doses in the two Sub-Counties since 2019. Therefore, raising public awareness of the importance of HPV vaccination could improve uptake.
基金Supported by the European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘Although the coronavirus disease 2019(COVID-19)pandemic was declared to be no longer“a public health emergency of international concern”with its wide range of clinical manifestations and late complications,severe acute respiratory syndrome coronavirus 2 infection proved to be a serious threat,especially to the elderly and patients with comorbidities.Patients with oncologic diseases are vulnerable to severe infection and death.Indeed,patients with oncohematological diseases have a higher risk of severe COVID-19 and impaired post-vaccination immunity.Unfortunately,cancer patients are usually excluded from vaccine trials and investigations of post-vaccinal immune responses and the effectiveness of the vaccines.We aimed to elucidate to what extent patients with cancer are at increased risk of developing severe COVID-19 and what is their overall case fatality rate.We also present the current concept and evidence on the effectiveness and safety of COVID-19 vaccines,including boosters,in oncology patients.In conclusion,despite the considerably higher mortality in the cancer patient group than the general population,countries with high vaccination rates have demonstrated trends toward improved survival of cancer patients early and late in the pandemic.
文摘This study aimed to examine the relationship between COVID-19 vaccine refusal and religiosity and fear of death among Muslims living in Turkey. This cross-sectional study was conducted online with 1046 adults aged 18 and older. The Ok-Religious Attitude Scale (Islam) (ORASI) (8 items) and Thorson-Powell Death Anxiety Scale (TPDAS) (20 items) were used as data collection instruments. The data were analyzed using the Pearson chi-square test, Student’s t-test, and binary logistic regression. A p-value of 0.05). In binary logistic regression analysis, vaccine rejection was 7.19 times higher among single people, 50.55 times higher among workers and tradesmen, and 3.36 times higher among people who did not have COVID-19. As religiosity increased, the risk of vaccine refusal decreased 1.037-fold.
文摘The technology behind vaccine development varies significantly from one vaccine to another depending on the time when the vaccine was first developed. Over the years, the vaccine innovation time has significantly shortened with the advancement of knowledge in the fields of molecular and cell biology, and discoveries in the field of biotechnology. The first vaccines created were tested in a kind of trial-and-error approach which sometimes had deadly side effects. These vaccines used either living, weakened, or completely dead pathogens. The use of whole pathogen vaccines was seen to be time consuming and unpredictable because even though it would cause an immune response, it could vary from person to person, and always had the risk of pathogens returning to virulence causing sometimes fatal outcomes. The next major technology used to create vaccines was subunit vaccines which utilize purified antigens inactivated through various methods. This technology is quite prevalent among the vaccines that are currently in circulation, making them quite effective, and free from fatal side effects. The viral vector vaccine technology has been around for a few decades and utilizes knowledge of molecular genetics to the greatest extent. It uses intermediate vectors to deliver genetic instructions to trigger an immune response within the subject body. The introduction of nucleic acid vaccines is the newest technology and has come to a great deal of attention during the SARS-CoV-2 immunization efforts. The technology primarily utilizes the delivery of genetic information using messenger ribonucleic acid (mRNA) to create characteristic pathogen-specific proteins that in turn generate an immune response in the recipients.
文摘Malignant tumors are still a worldwide threat to human health.Tumor treatment strategies are constantly evolving,and the advent of tumor immunotherapy has brought up hope to many types of tumors,especially for those that are refractory to conventional therapies including surgery,radiotherapy,and chemotherapy.Tumor vaccines can initiate or amplify an anti-tumor immune response in tumor patients through active immunization,and therefore occupy an important position in tumor immunotherapy.The main types of tumor vaccines include tumor cell vaccines,dendritic cell vaccines,polypeptide vaccines and nucleic acid vaccines.Due to factors such as poor antigen selection and suppressive tumor microenvironment,earliest tumor vaccines on clinical trials failed to achieve satisfactory clinical effects.However,with the development of second-generation genome sequencing technologies and bioinformatics tools,it is possible to predict neoantigens generated by tumor-specific mutations and therefore prepare personalized vaccines.This article summarizes the global efforts in developing tumor vaccines and highlights several representative tumor vaccines in each category.
基金support of the Zhejiang Medicine and Health Technology project (2022KY716)
文摘Objective:To examine COVID-19 vaccine uptake and its determinants among teenagers and their parents in Zhejiang,China.Methods:An online cross-sectional study was conducted among parents of teenagers in Zhejiang,China from May 1 to 31,2022.Data were interpreted via univariate and multivariate analyses using the statistical package for the social sciences(SPSS)program.Results:A total of 11115(96.11%)participants and 11449(99.00%)of their children in Zhejiang,China had been vaccinated against COVID-19.Children whose parents did not receive COVID-19 vaccination were 19 times(aOR 18.96,95%CI 12.36-29.08)more likely to be unvaccinated than their counterparts.In addition,children with no previous influenza vaccination,those whose parents doubted the COVID-19 vaccine’s safety or effectiveness,were 6.11 times(aOR 6.11,95%CI 2.80-13.34),8.27 times(aOR 8.27,95%CI 5.33-12.83),and 2.69 times(aOR 2.69,95%CI 1.11-6.50)more likely to be unvaccinated than their counterparts,respectively.COVID-19 vaccine uptake varied between different sociodemographic groups.However,the odds of receiving the COVID-19 vaccine decreased as age and education level increased.The main refusal reasons claimed by participants were that they had medical conditions that may not qualify them for vaccination(53.78%),followed by safety concerns about the vaccine(13.56%),not knowing where to get vaccinated(6.44%),and concerns about fertility issues(5.56%).Conclusions:Despite a highly encouraging level of COVID-19 vaccine uptake in Zhejiang,China,the elderly and highly educated people had lower COVID-19 vaccine uptake.It is suggested that tailored health education strategies should be taken to increase the COVID-19 vaccine uptake in such groups.Furthermore,with vaccination rates at such a high level,the pandemic is still ongoing,and public confidence in vaccines may decline.Thus,sufficient evidence-based information regarding COVID-19 vaccines should be provided to the public.
基金supported by the National Natural Science Foundation of China(31970696,81502975,81830089,U20A20378,82188102)the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(LR22H160010)+2 种基金the National Key Research and Development Program(2019YFC1316000)the Zhejiang Provincial Key Research and Development Program(2019C03019)the Zhejiang Provincial College Student Science and Technology Innovation Activity Plan-College Student Innovation and Entrepreneurship Incubation Program(Young Talent Program)(2022R40122)。
文摘Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunotherapeutic strategy has attracted much attention for various diseases,however,its application in CHOL is limited due to the thoughtlessness in the integration of vaccine design and patient selection.A recent study established an integrated path for identifying potent CHOL antigens for mRNA vaccine development and a precise stratification for identifying CHOL patients who can benefit from the mRNA vaccines.In spite of a promising prospect,further investigations should identify immunogenic antigens and onco-immunological characteristics of CHOL to guide the clinical application of CHOL mRNA vaccines in the future.
基金Supported by the National Natural Science Foundation of China(No.32102824)the Zhejiang Provincial Natural Science Foundation of China(No.LQ18B060005)the Zhejiang Sci-Tech University Foundation(Nos.11612932611702,11612832611909)。
文摘Aeromonas hydrophila is a Gram-negative pathogen that can infect various fish,including largemouth bass(Micropterus salmoides),which have caused huge economic losses.In present study,largemouth bass anti-A.hydrophila antibodies were produced,then a highly immunogenic outer membrane proteins,AHA_3793,was identified by combined western blotting and mass spectrometry analysis.Moreover,AHA_3793 was expressed,and its immunogenicity was further verified by western blotting.Subsequently,the protective efficacy of AHA_3793 were evaluated in largemouth bass.The results showed that rAHA_3793 could produce a relative percentage survival(RPS)of 61.76% for largemouth bass against A.hydrophila challenge.ELISA analysis showed the specific serum antibodies of largemouth bass against rAHA_3793 and A.hydrophila in vaccinated group in weeks 4 and 5 after immunization were significantly higher than those in control group,which suggested that rAHA_3793 induced production of specific serum antibodies against rAHA_3793 and A.hydrophila.The qRT-PCR analysis showed that expressions of CD4-2 and MHC Ⅱα were also significantly up-regulated after immunization.These results collectively demonstrated that rAHA_3793 could induce a strong humoral immune response of largemouth bass,and then produce high immune protection ef fects against A.hydrophila infection.
基金supported by the Fish Innovation Team of Shandong Agriculture Research System (No. SDAIT-1206)the Aquatic Animal Immunologic Agents Engineering Research Center of Shandong Province, the Qingdao Agricultural University Doctoral Start-Up Fund (6631122030)+5 种基金the National Natural Science Foundation of China (No. 32002421)the Advanced Talents Foundation of QAU (No. 6651118016)the Natural Science Foundation of Shandong Province (No. ZR2019BC009)the ‘First-Class Fishery Discipline’ program of Shandong Province, the special top talent plan ‘One Thing One Decision (Yi Shi Yi Yi)’the Key Research and Development Program in Shandong Province (No. 2018YFJH0703)Breeding Plan of Shandong Provincial Qingchuang Research Team (2019)
文摘Vibrio scophthalmi and Aeromonas salmonicida can cause high turbot mortality and huge economic losses.Presently,vaccination is the most promising method for preventing communicable diseases.In this study,we used formalin to kill V.scophthalmi and A.salmonicida cells,and mixed with the mineralized oil adjuvant(Montanide^(TM)ISA 763 AVG)to prepare the bivalent inactivated vaccine.The results showed that turbot inoculated with the bivalent inactivated vaccine exhibited strong tolerance to the infection of V.scophthalmi and A.salmonicida,and no obvious clinical symptoms and pathological changes were observed.The activities of enzymes lysozyme,acid phosphatase and complement C3 had significantly increased after the vaccination.The antibody titer response of vaccinated turbot was greatly boosted,which was positively connected with the immunological impact according to ELISA results.Simultaneously,the expression levels of immune-related genes such as MHC-IIα,MHC-IIβ,CD4,CD8,TNF-αand IL^(-1)βwere up-regulated,demonstrating that it might stimulate humoral and cellular immunological response in turbot.These findings highlight the potential of the bivalent inactivated vaccine for controlling V.scophthalmi and A.salmonicida infections in turbot.
基金supported by Natural Science Foundation of Shaanxi Province(Grant No.:2019ZY-CXPT-03-01)to Ping Zhu and Key Research and Development Program of Shaanxi Province(Grant No.:2020ZDLSF03-02)to Zhi-Nan Chen and Huijie Bian as well as Tricision Biotherapeutics Inc.
文摘Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4t and CD8t T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.
文摘Objective:To assess the knowledge of healthcare workers on the measles vaccine and its cold chain management.Method:An institutional-based cross-sectional study was conducted from February 1 to March 30,2022 in Gondar City Administration public health institutions among 165 healthcare workers.Data were collected using a structured questionnaire.In addition,an on-spot observation checklist was used to assess the availability,status and management of the cold chain.A logistic regression model was used to assess the relationship between the outcome and predictor variables.Crude and adjusted odds ratios were calculated with 95%confidence intervals.Results:Overall,87(52.7%;95%CI 44.8%-60.5%)of the healthcare workers had unsatisfactory knowledge regarding the measles vaccine and its cold chain management.One hundred thirty-six(82.4%)healthcare workers correctly mentioned the recommended range of temperature(2-8℃)for measles vaccine storage.Healthcare workers aged 18-29 years(P=0.001)and 30-44 years(P=0.014)were observed as determinants of unsatisfactory knowledge on the measles vaccine and its cold chain management.One hundred and five(63.6%)of the healthcare workers did not correctly mention the type of measles vaccine used in routine immunization.More than one-third(36.4%)of the healthcare workers perceived that the measles vaccine is not safe and could cause measles.Conclusions:More than half of the healthcare workers in the study area had unsatisfactory knowledge on the measles vaccine and its cold chain management.It is necessary to provide technical support and in-service training for healthcare workers to ensure optimal immunization effectiveness.
