BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HA...BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HAV,as evident by cases of acute hepatitis due to HAV among adults.AIM To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus(HEV)infection.METHODS This was a trend analysis conducted at Aga Khan University Hospital Karachi(Sindh,Pakistan)from February 2024 to May 2024.Individuals aged 18 years and older diagnosed with acute viral hepatitis attributed to hepatotropic viruses in 2024 were reviewed.To compare the trend patients admitted with acute hepatitis during 2019-2023 were also reviewed.Data regarding clinical and laboratory parameters were recorded.The yearly trend of acute hepatitis due to HAV and HEV was analyzed,and comparative analysis was done between HAV and HEV cases among adults.RESULTS A total of 396 patients were found to have acute hepatitis during our study duration.HAV was diagnosed in 234 patients(59%)while 157 patients(39.6%)were found to have acute HEV infection.Additionally,acute hepatitis B virus infection was identified in 3 patients(0.7%),whereas acute hepatitis C virus infection was found in 2(0.5%)cases of acute hepatitis.Yearly trends showed increasing occurrence of HAV infection among adults over last 5 years.The patients with acute HAV were younger than patients with HEV(28 years±8 years vs 30 years±8 years;P<0.01).Higher levels of total bilirubin were seen in HEV infection,while higher levels of alanine transaminase were seen in HAV infection.However,a higher proportion of acute liver failure(ALF),coagulopathy,and mortality were observed in HEV.CONCLUSION An increase in acute hepatitis A cases among adults shows less severity than hepatitis E,highlighting the need for better sanitation,hygiene,and adult hepatitis A vaccination programs.展开更多
Immunoprophylaxis is routinely recommended for infants born to mothers with hepatitis B virus(HBV)infection within the first 12-24 hours.Detection of he-patitis B surface antibody(HBsAb)resulting from hepatitis B immu...Immunoprophylaxis is routinely recommended for infants born to mothers with hepatitis B virus(HBV)infection within the first 12-24 hours.Detection of he-patitis B surface antibody(HBsAb)resulting from hepatitis B immunoglobulin administered at birth may be perceived as a real vaccine response.This makes it difficult to detect HBV infection.For this reason,it is recommended that infants born to hepatitis B surface antigen positive mothers and who received immunop-rophylaxis at birth should have HBsAb testing when they are 9-15 months old.展开更多
Hepatitis B virus(HBV)infection causes acute and chronic hepatitis,compensated and decompensated cirrhosis,and hepatocellular carcinoma worldwide.The actual status of HBV infection and its treatment in certain regions...Hepatitis B virus(HBV)infection causes acute and chronic hepatitis,compensated and decompensated cirrhosis,and hepatocellular carcinoma worldwide.The actual status of HBV infection and its treatment in certain regions of Asian and African countries,including Ethiopia,has not been well-documented thus far.Antiviral therapy for HBV infection can prevent the progression of HBV-related liver diseases and decrease the HBV-related symptoms,such as abdominal symp-toms,fatigue,systemic symptoms and others.In Eastern Ethiopia,HBV-infected patients with cirrhosis were found to be positive for the HBV e antigen and to have a higher viral load than those without cirrhosis.Notably,54.4%of patients practiced khat chewing and 18.1%consumed excessive amounts of alcohol.Teno-fovir disoproxil fumarate effectively suppressed HBV DNA in those infected with HBV.It is important to elucidate the actual status of HBV infection in Eastern Ethiopia to eliminate HBV infection worldwide by 2030.HBV vaccination and the educational programs for Health Science students that provide practical strategies could help to reduce HBV infection in Eastern Ethiopia.展开更多
For the first time in human history,hundreds of millions of people all over the world have been subjected to compulsory vaccination with a new type of nucleic acid based vaccines in order to keep their jobs or be able...For the first time in human history,hundreds of millions of people all over the world have been subjected to compulsory vaccination with a new type of nucleic acid based vaccines in order to keep their jobs or be able to travel due to some notorious coronavirus disease 2019(COVID-19)mandates.The vast majority of African countries were either initially deprived of these vaccines,or later,a majority of the population was too skeptical to receive them and preferred a safe early treatment pharmacological approach.Yet,Africa had the lowest COVID-19 mortality rate compared to those countries that adopted mass vaccination.This letter to the editor adds African insights that should be helpful in future pandemics to save millions of precious lives.展开更多
The Salmonella pathogenicity islands(SPIs) play crucial roles in the progression of Salmonella infection. In this study, we constructed an improved λ Red homologous recombination system to prepare single and triple d...The Salmonella pathogenicity islands(SPIs) play crucial roles in the progression of Salmonella infection. In this study, we constructed an improved λ Red homologous recombination system to prepare single and triple deletion mutants of 3 prominent SPIs(SPI-1, 2, and 3), aiming at the impact of deletion on morphology, carbon source metabolism, adhesion and invasion capacity, in vivo colonization, and immune efficacy in chicks. Our examination revealed that the surface of the single deletion mutants(SM6ΔSPI1, ΔSPI2, and ΔSPI3) exhibited a more rugged texture and appeared to be enveloped in a layer of transparent colloid, whereas the morphology of the triple deletion mutant(SM6ΔSPI1&2&3) remained unaltered when compared to the parent strain. The carbon metabolic spectrum of the SPI mutants underwent profound alterations, with a notable and statistically significant modification observed in 30 out of 95 carbon sources, primarily carbohydrates(17 out of 30). Furthermore, the adhesion capacity of the 4 mutants to Caco-2 cells was significantly reduced when compared to that of the parent strain. Moreover,the invasion capacity of mutants SM6ΔSPI1 and SM6ΔSPI1&2&3 exhibited a substantial decrease, while it was enhanced to varying degrees for SM6ΔSPI3 and SM6ΔSPI2. Importantly, none of the 4 mutants induced any clinical symptoms in the chicks. However, they did transiently colonize the spleen and liver. Notably, the SM6ΔSPI1&2&3mutant was rapidly cleared from both the spleen and liver within 8 days post-infection and no notable pathological changes were observed in the organs. Additionally, when challenged, the mutants immunized groups displayed a significant increase in antibody levels and alterations in the CD3+CD4+ and CD3+CD8+ subpopulations, and the levels of IL-4 and IFN-γ cytokines in the SM6ΔSPI1&2&3 immunized chicken serum surpassed those of other groups.In summary, the successful construction of the 4 SPI mutants lays the groundwork for further exploration into the pathogenic(including metabolic) mechanisms of SPIs and the development of safe and effective live attenuated Salmonella vaccines or carriers.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
Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk fac...Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.展开更多
The stamping-out strategy has been used to control highly pathogenic avian influenza viruses in many countries,driven by the belief that vaccination would not be successful against such viruses and fears that avian in...The stamping-out strategy has been used to control highly pathogenic avian influenza viruses in many countries,driven by the belief that vaccination would not be successful against such viruses and fears that avian influenza virus in vaccinated birds would evolve more rapidly and pose a greater risk to humans.In this review,we summarize the successes in controlling highly pathogenic avian influenza in China and make suggestions regarding the requirements for vaccine selection and effectiveness.In addition,we present evidence that vaccination of poultry not only eliminates human infection with avian influenza virus,but also significantly reduces and abolishes some harmful characteristics of avian influenza virus.展开更多
Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficie...Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine efficacy.SKN showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,respectively.Compared with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival rates.Mycobacterium smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis results.Collectively,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.展开更多
Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome corona...Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related complications.Therefore,COVID-19 vaccination has been recommended to be administered as early as possible in LTRs.Data sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in PubMed.Results:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination.Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained unresponsive.Furthermore,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver injury.Conclusions:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.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
Bordetella bronchiseptica(Bb)is recognized as a leading cause of respiratory diseases in dogs and cats.However,epidemiological data on Bb in dogs and cats in China are still limited,and there is no commercially availa...Bordetella bronchiseptica(Bb)is recognized as a leading cause of respiratory diseases in dogs and cats.However,epidemiological data on Bb in dogs and cats in China are still limited,and there is no commercially available vaccine.Live vaccines containing Bb that are widely used abroad are generally efective but can establish latency and potentially reactivate to cause illness in some immunodefcient vaccinated recipients,raising safety concerns.In this study,34 canine-derived and two feline-derived Bb strains were isolated from 1809 canine and 113 feline nasopharyngeal swab samples collected from eight provinces in China from 2021 to 2023.The PCR results showed that the percentage of positive Bb was 22.94%(441/1922),and more than 90%of the Bb isolates had four virulence factor-encoding genes(VFGs),namely,fhaB,prn,betA and dnt.All the isolated strains displayed a multidrug-resistant phenotype.The virulence of 10 Bb strains isolated from dogs with respiratory symptoms was tested in mice,and we found that eight isolates were highly virulent.Furthermore,the eight Bb isolates with high virulence were inactivated and intramuscularly injected into mice,and three Bb strains(WH1218,WH1203 and WH1224)with the best protective efcacy were selected.Dogs immunized with these three strains exhibited strong protection against challenge with the Bb feld strain WH1218.Ultimately,the WH1218 strain with the greatest protection in dogs was selected as the vaccine candidate.Dogs and cats that received a vaccine containing 109 CFU of the inactivated WH1218 strain showed complete protection against challenge with the Bb feld strain WH1218.This study revealed that Bb is an important pathogen that causes respiratory diseases in domestic dogs and cats in China,and all the isolates exhibited multidrug resistance.The present work contributes to the current understanding of the prevalence,antimicrobial resistance,and virulence genes of Bb in domestic dogs and cats.Additionally,our results suggest that the WH1218 strain is a promising candidate safe and efcacious inactivated Bb vaccine.展开更多
Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor reg...Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.展开更多
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
Objective The present study aimed to evaluate the immunogenicity of BA.2 variant receptor binding domain(RBD)recombinant protein formulated with CpG 1826 plus alum dual adjuvant.Methods The BA.2 variant RBD(residues 3...Objective The present study aimed to evaluate the immunogenicity of BA.2 variant receptor binding domain(RBD)recombinant protein formulated with CpG 1826 plus alum dual adjuvant.Methods The BA.2 variant RBD(residues 308-548)fusing TT-P2 epitope was obtained from prokaryotic expression system,purification technology and dialysis renaturation,which was designated as Sot protein.The soluble Sot protein formulated with CpG 1826 plus alum dual adjuvant was designated as Sot/CA subunit vaccine and then the BALB/c mice were intramuscularly administrated with two doses of the Sot/CA subunit vaccine at 14-day interval(day 0 and 14).On day 28,the number of effector T lymphocytes secreting IFN-γand IL-4 in mice spleen were determined by enzyme-linked immunospot(ELISpot)assay.The serum IgG,IgG1 and IgG2a antibodies were examined by enzyme-linked immunosorbent assay(ELISA).In addition,the level of neutralizing antibodies(NAbs)induced by Sot/CA subunit vaccine was also evaluated by the microneutralization assay.Results The high-purity soluble Sot protein with antigenicity was successfully obtained by the prokaryotic expression,protein purification and dialysis renaturation.The Sot/CA subunit vaccine induced a high level of IgG antibodies and NAbs,which were of cross-neutralizing activity against SARS-CoV-2 BA.2 and XBB.1.5 variants.Meanwhile,Sot/CA subunit vaccine also induced a high level of effector T lymphocytes secreting IFN-γ(635.00±17.62)and IL-4(279.20±13.10),respectively.Combined with a decreased IgG1/IgG2a ratio in the serum,which indicating Sot/CA subunit vaccine induced a Th1-type predominant immune response.Conclusion The Sot protein formulated with CpG 1826 plus alum dual adjuvant showed that the excellent cellular and humoral immunogenicity,which provided a scientific basis for the development of BA.2 variant subunit vaccines and references for the adjuvant application of subunit vaccines.展开更多
This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines.Data on malaria vaccine development was collected thro...This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines.Data on malaria vaccine development was collected through a comprehensive review.The literature search was performed using databases including Google Scholar,PubMed,NIH,and Web of Science.Various novel approaches of vaccination are being developed,including those based on radiation-attenuated strategies,monoclonal antibodies,targeted immunogenic peptides,RNA and DNA vaccines,nanoparticle-based vaccines,protein-based vaccination protocols,and whole organism-based vaccination strategies.Trials on RTS,S have entered phase Ⅲtesting,and those based on blood-stage vaccines and vaccines to interrupt malarial transmission have advanced to higher stages of trials.Mathematical modeling,combined drug and vaccine strategies,mass drug administration,polyvalent vaccine formulations,and targeted vaccination campaigns is playing an important role in malarial prevention.Furthermore,assessing coverage,accessibility,acceptability,deployment,compilation,and adherence to specific vaccination strategies in endemic regions is essential for vaccination drives against malaria.展开更多
Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillan...Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.展开更多
A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza vaccines.In this study,a strategy called computationally optimized broadly react...A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza vaccines.In this study,a strategy called computationally optimized broadly reactive antigen(COBRA)was used to generate a consensus sequence of the hemagglutinin globular head portion(HA1)of influenza virus samples collected from 1918 to 2021 to trace evolutionary changes and incorporate them into the designed constructs.Constructs carrying different HA1regions were delivered into eukaryotic cells by Salmonella-mediated bactofection using a Semliki Forest virus RNA-dependent RNApolymerase(RdRp)-based eukaryotic expression system,pJHL204.Recombinant protein expression was confirmed by Western blot and immunofluorescence assays.Mice immunized with the designed constructs produced a humoral response,with a significant increase in immunoglobulin G(IgG)levels,and a cell-mediated immune response,including a 1.5-fold increase in CD4^(+) and CD8^(+)T cells.Specifically,constructs #1 and #5 increased the production of interferon-γ(IFN-γ)producing CD4^(+)and CD8^(+)T cells,skewing the response toward the T helper type 1 cell(Th1)pathway.Additionally,interleukin-4(IL-4)-producing T cells were upregulated 4-fold.Protective efficacy was demonstrated,with up to 4-fold higher production of neutralizing antibodies and a hemagglutination inhibition titer>40 against the selected viral strains.The designed constructs conferred a broadly protective immune response,resulting in a notable reduction in viral titer and minimal inflammation in the lungs of mice challenged with the influenza A/PR8/34,A/Brisbane/59/2007,A/California/07/2009,KBPV VR-92,and NCCP 43021 strains.This discovery revolutionizes influenza vaccine design and delivery;Salmonella-mediated COBRA-HA1 is a highly effective in vivo antigen presentation strategy.This approach can effectively combat seasonal H1N1 influenza strains and potential pandemic outbreaks.展开更多
BACKGROUND Patients with diabetes mellitus(DM)are predisposed to an increased risk of infection signifying the importance of vaccination to protect against its potentially severe complications.The Centers for Disease ...BACKGROUND Patients with diabetes mellitus(DM)are predisposed to an increased risk of infection signifying the importance of vaccination to protect against its potentially severe complications.The Centers for Disease Control and Prevention/Advisory Committee on Immunization Practices(CDC/ACIP)issued immunization recommendations to protect this patient population.AIM To assess the adherence of patients with DM to the CDC/ACIP immunization recommendations in Saudi Arabia and to identify the factors associated with the vaccine adherence rate.METHODS An observational retrospective study conducted in 2023 was used to collect data on the vaccination records from 13 diabetes care centers in Saudi Arabia with 1000 eligible patients in phase I with data collected through chart review and 709 patients in phase II through online survey.RESULTS Among participants,10.01%(n=71)had never received any vaccine,while 85.89%(n=609)received at least one dose of the coronavirus disease 2019(COVID-19)vaccine,and 34.83%(n=247)had received the annual influenza vaccine.Only 2.96%(n=21),2.11%(n=15),and 1.12%(n=8)received herpes zoster,tetanus,diphtheria,and pertussis(Tdap),and human papillomavirus(HPV)vaccines,respectively.For patients with DM in Saudi Arabia,the rate of vaccination for annual influenza and COVID-19 vaccines was higher compared to other vaccinations such as herpes zoster,Tdap,pneumococcal,and HPV.Factors such as vaccine recommendations provided by family physicians or specialists,site of care,income level,DM-related hospitalization history,residency site,hemoglobin A1c(HbA1c)level,and health sector type can significantly influence the vaccination rate in patients with DM.Among non-vaccinated patients with DM,the most reported barriers were lack of knowledge and fear of side effects.This signifies the need for large-scale research in this area to identify additional factors that might facilitate adherence to CDC/ACIP vaccine recommendations in patients with DM.CONCLUSION In Saudi Arabia,patients with DM showed higher vaccination rates for annual influenza and COVID-19 vaccines compared to other vaccinations such as herpes zoster,Tdap,pneumococcal,and HPV.Factors such as vaccine recommendations provided by family physicians or specialists,the site of care,income level,DM-related hospitalization history,residency site,HbA1c level,and health sector type can significantly influence the vaccination rate in patients with DM.展开更多
Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances withi...Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.展开更多
文摘BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HAV,as evident by cases of acute hepatitis due to HAV among adults.AIM To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus(HEV)infection.METHODS This was a trend analysis conducted at Aga Khan University Hospital Karachi(Sindh,Pakistan)from February 2024 to May 2024.Individuals aged 18 years and older diagnosed with acute viral hepatitis attributed to hepatotropic viruses in 2024 were reviewed.To compare the trend patients admitted with acute hepatitis during 2019-2023 were also reviewed.Data regarding clinical and laboratory parameters were recorded.The yearly trend of acute hepatitis due to HAV and HEV was analyzed,and comparative analysis was done between HAV and HEV cases among adults.RESULTS A total of 396 patients were found to have acute hepatitis during our study duration.HAV was diagnosed in 234 patients(59%)while 157 patients(39.6%)were found to have acute HEV infection.Additionally,acute hepatitis B virus infection was identified in 3 patients(0.7%),whereas acute hepatitis C virus infection was found in 2(0.5%)cases of acute hepatitis.Yearly trends showed increasing occurrence of HAV infection among adults over last 5 years.The patients with acute HAV were younger than patients with HEV(28 years±8 years vs 30 years±8 years;P<0.01).Higher levels of total bilirubin were seen in HEV infection,while higher levels of alanine transaminase were seen in HAV infection.However,a higher proportion of acute liver failure(ALF),coagulopathy,and mortality were observed in HEV.CONCLUSION An increase in acute hepatitis A cases among adults shows less severity than hepatitis E,highlighting the need for better sanitation,hygiene,and adult hepatitis A vaccination programs.
文摘Immunoprophylaxis is routinely recommended for infants born to mothers with hepatitis B virus(HBV)infection within the first 12-24 hours.Detection of he-patitis B surface antibody(HBsAb)resulting from hepatitis B immunoglobulin administered at birth may be perceived as a real vaccine response.This makes it difficult to detect HBV infection.For this reason,it is recommended that infants born to hepatitis B surface antigen positive mothers and who received immunop-rophylaxis at birth should have HBsAb testing when they are 9-15 months old.
文摘Hepatitis B virus(HBV)infection causes acute and chronic hepatitis,compensated and decompensated cirrhosis,and hepatocellular carcinoma worldwide.The actual status of HBV infection and its treatment in certain regions of Asian and African countries,including Ethiopia,has not been well-documented thus far.Antiviral therapy for HBV infection can prevent the progression of HBV-related liver diseases and decrease the HBV-related symptoms,such as abdominal symp-toms,fatigue,systemic symptoms and others.In Eastern Ethiopia,HBV-infected patients with cirrhosis were found to be positive for the HBV e antigen and to have a higher viral load than those without cirrhosis.Notably,54.4%of patients practiced khat chewing and 18.1%consumed excessive amounts of alcohol.Teno-fovir disoproxil fumarate effectively suppressed HBV DNA in those infected with HBV.It is important to elucidate the actual status of HBV infection in Eastern Ethiopia to eliminate HBV infection worldwide by 2030.HBV vaccination and the educational programs for Health Science students that provide practical strategies could help to reduce HBV infection in Eastern Ethiopia.
文摘For the first time in human history,hundreds of millions of people all over the world have been subjected to compulsory vaccination with a new type of nucleic acid based vaccines in order to keep their jobs or be able to travel due to some notorious coronavirus disease 2019(COVID-19)mandates.The vast majority of African countries were either initially deprived of these vaccines,or later,a majority of the population was too skeptical to receive them and preferred a safe early treatment pharmacological approach.Yet,Africa had the lowest COVID-19 mortality rate compared to those countries that adopted mass vaccination.This letter to the editor adds African insights that should be helpful in future pandemics to save millions of precious lives.
基金supported by the National KeyR&DProgramof China(2022YFF0710500)the National Natural Science Foundation of China(32172853 and 32373013)the Central Public-interest Scientific Institution Basal Research Fund,China(1610302022001).
文摘The Salmonella pathogenicity islands(SPIs) play crucial roles in the progression of Salmonella infection. In this study, we constructed an improved λ Red homologous recombination system to prepare single and triple deletion mutants of 3 prominent SPIs(SPI-1, 2, and 3), aiming at the impact of deletion on morphology, carbon source metabolism, adhesion and invasion capacity, in vivo colonization, and immune efficacy in chicks. Our examination revealed that the surface of the single deletion mutants(SM6ΔSPI1, ΔSPI2, and ΔSPI3) exhibited a more rugged texture and appeared to be enveloped in a layer of transparent colloid, whereas the morphology of the triple deletion mutant(SM6ΔSPI1&2&3) remained unaltered when compared to the parent strain. The carbon metabolic spectrum of the SPI mutants underwent profound alterations, with a notable and statistically significant modification observed in 30 out of 95 carbon sources, primarily carbohydrates(17 out of 30). Furthermore, the adhesion capacity of the 4 mutants to Caco-2 cells was significantly reduced when compared to that of the parent strain. Moreover,the invasion capacity of mutants SM6ΔSPI1 and SM6ΔSPI1&2&3 exhibited a substantial decrease, while it was enhanced to varying degrees for SM6ΔSPI3 and SM6ΔSPI2. Importantly, none of the 4 mutants induced any clinical symptoms in the chicks. However, they did transiently colonize the spleen and liver. Notably, the SM6ΔSPI1&2&3mutant was rapidly cleared from both the spleen and liver within 8 days post-infection and no notable pathological changes were observed in the organs. Additionally, when challenged, the mutants immunized groups displayed a significant increase in antibody levels and alterations in the CD3+CD4+ and CD3+CD8+ subpopulations, and the levels of IL-4 and IFN-γ cytokines in the SM6ΔSPI1&2&3 immunized chicken serum surpassed those of other groups.In summary, the successful construction of the 4 SPI mutants lays the groundwork for further exploration into the pathogenic(including metabolic) mechanisms of SPIs and the development of safe and effective live attenuated Salmonella vaccines or carriers.
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.
文摘Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.
基金This work was supported by the National Key Research andDevelopment Programof China(2021YFD1800200 and2021YFC2301700).
文摘The stamping-out strategy has been used to control highly pathogenic avian influenza viruses in many countries,driven by the belief that vaccination would not be successful against such viruses and fears that avian influenza virus in vaccinated birds would evolve more rapidly and pose a greater risk to humans.In this review,we summarize the successes in controlling highly pathogenic avian influenza in China and make suggestions regarding the requirements for vaccine selection and effectiveness.In addition,we present evidence that vaccination of poultry not only eliminates human infection with avian influenza virus,but also significantly reduces and abolishes some harmful characteristics of avian influenza virus.
基金supported by grants from the Natural Science Foundation of Huai'an Science and Technology Bureau(Grant No.HAB202312)the Science and Technology Development Fund of the Affiliated Hospital of Xuzhou Medical University(Grant No.XYFY2021018).
文摘Tumor vaccines are a promising avenue in cancer immunotherapy.Despite the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the treatment.Here,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine efficacy.SKN showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,respectively.Compared with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival rates.Mycobacterium smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis results.Collectively,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.
基金the National Natural Science Foundation of China(82103662).
文摘Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related complications.Therefore,COVID-19 vaccination has been recommended to be administered as early as possible in LTRs.Data sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in PubMed.Results:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination.Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained unresponsive.Furthermore,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver injury.Conclusions:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.
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.
基金the Guangdong Major Project of Basic and Applied Basic Research(2020B0301030007).
文摘Bordetella bronchiseptica(Bb)is recognized as a leading cause of respiratory diseases in dogs and cats.However,epidemiological data on Bb in dogs and cats in China are still limited,and there is no commercially available vaccine.Live vaccines containing Bb that are widely used abroad are generally efective but can establish latency and potentially reactivate to cause illness in some immunodefcient vaccinated recipients,raising safety concerns.In this study,34 canine-derived and two feline-derived Bb strains were isolated from 1809 canine and 113 feline nasopharyngeal swab samples collected from eight provinces in China from 2021 to 2023.The PCR results showed that the percentage of positive Bb was 22.94%(441/1922),and more than 90%of the Bb isolates had four virulence factor-encoding genes(VFGs),namely,fhaB,prn,betA and dnt.All the isolated strains displayed a multidrug-resistant phenotype.The virulence of 10 Bb strains isolated from dogs with respiratory symptoms was tested in mice,and we found that eight isolates were highly virulent.Furthermore,the eight Bb isolates with high virulence were inactivated and intramuscularly injected into mice,and three Bb strains(WH1218,WH1203 and WH1224)with the best protective efcacy were selected.Dogs immunized with these three strains exhibited strong protection against challenge with the Bb feld strain WH1218.Ultimately,the WH1218 strain with the greatest protection in dogs was selected as the vaccine candidate.Dogs and cats that received a vaccine containing 109 CFU of the inactivated WH1218 strain showed complete protection against challenge with the Bb feld strain WH1218.This study revealed that Bb is an important pathogen that causes respiratory diseases in domestic dogs and cats in China,and all the isolates exhibited multidrug resistance.The present work contributes to the current understanding of the prevalence,antimicrobial resistance,and virulence genes of Bb in domestic dogs and cats.Additionally,our results suggest that the WH1218 strain is a promising candidate safe and efcacious inactivated Bb vaccine.
基金funding from the Liaoning Province Doctoral Start-up(grant number 2023-BS-086).
文摘Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.
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funded by the National Key R&D Program of China(2023YFC2605302).
文摘Objective The present study aimed to evaluate the immunogenicity of BA.2 variant receptor binding domain(RBD)recombinant protein formulated with CpG 1826 plus alum dual adjuvant.Methods The BA.2 variant RBD(residues 308-548)fusing TT-P2 epitope was obtained from prokaryotic expression system,purification technology and dialysis renaturation,which was designated as Sot protein.The soluble Sot protein formulated with CpG 1826 plus alum dual adjuvant was designated as Sot/CA subunit vaccine and then the BALB/c mice were intramuscularly administrated with two doses of the Sot/CA subunit vaccine at 14-day interval(day 0 and 14).On day 28,the number of effector T lymphocytes secreting IFN-γand IL-4 in mice spleen were determined by enzyme-linked immunospot(ELISpot)assay.The serum IgG,IgG1 and IgG2a antibodies were examined by enzyme-linked immunosorbent assay(ELISA).In addition,the level of neutralizing antibodies(NAbs)induced by Sot/CA subunit vaccine was also evaluated by the microneutralization assay.Results The high-purity soluble Sot protein with antigenicity was successfully obtained by the prokaryotic expression,protein purification and dialysis renaturation.The Sot/CA subunit vaccine induced a high level of IgG antibodies and NAbs,which were of cross-neutralizing activity against SARS-CoV-2 BA.2 and XBB.1.5 variants.Meanwhile,Sot/CA subunit vaccine also induced a high level of effector T lymphocytes secreting IFN-γ(635.00±17.62)and IL-4(279.20±13.10),respectively.Combined with a decreased IgG1/IgG2a ratio in the serum,which indicating Sot/CA subunit vaccine induced a Th1-type predominant immune response.Conclusion The Sot protein formulated with CpG 1826 plus alum dual adjuvant showed that the excellent cellular and humoral immunogenicity,which provided a scientific basis for the development of BA.2 variant subunit vaccines and references for the adjuvant application of subunit vaccines.
文摘This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines.Data on malaria vaccine development was collected through a comprehensive review.The literature search was performed using databases including Google Scholar,PubMed,NIH,and Web of Science.Various novel approaches of vaccination are being developed,including those based on radiation-attenuated strategies,monoclonal antibodies,targeted immunogenic peptides,RNA and DNA vaccines,nanoparticle-based vaccines,protein-based vaccination protocols,and whole organism-based vaccination strategies.Trials on RTS,S have entered phase Ⅲtesting,and those based on blood-stage vaccines and vaccines to interrupt malarial transmission have advanced to higher stages of trials.Mathematical modeling,combined drug and vaccine strategies,mass drug administration,polyvalent vaccine formulations,and targeted vaccination campaigns is playing an important role in malarial prevention.Furthermore,assessing coverage,accessibility,acceptability,deployment,compilation,and adherence to specific vaccination strategies in endemic regions is essential for vaccination drives against malaria.
文摘Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.
基金Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2019R1A6A1A03033084).
文摘A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza vaccines.In this study,a strategy called computationally optimized broadly reactive antigen(COBRA)was used to generate a consensus sequence of the hemagglutinin globular head portion(HA1)of influenza virus samples collected from 1918 to 2021 to trace evolutionary changes and incorporate them into the designed constructs.Constructs carrying different HA1regions were delivered into eukaryotic cells by Salmonella-mediated bactofection using a Semliki Forest virus RNA-dependent RNApolymerase(RdRp)-based eukaryotic expression system,pJHL204.Recombinant protein expression was confirmed by Western blot and immunofluorescence assays.Mice immunized with the designed constructs produced a humoral response,with a significant increase in immunoglobulin G(IgG)levels,and a cell-mediated immune response,including a 1.5-fold increase in CD4^(+) and CD8^(+)T cells.Specifically,constructs #1 and #5 increased the production of interferon-γ(IFN-γ)producing CD4^(+)and CD8^(+)T cells,skewing the response toward the T helper type 1 cell(Th1)pathway.Additionally,interleukin-4(IL-4)-producing T cells were upregulated 4-fold.Protective efficacy was demonstrated,with up to 4-fold higher production of neutralizing antibodies and a hemagglutination inhibition titer>40 against the selected viral strains.The designed constructs conferred a broadly protective immune response,resulting in a notable reduction in viral titer and minimal inflammation in the lungs of mice challenged with the influenza A/PR8/34,A/Brisbane/59/2007,A/California/07/2009,KBPV VR-92,and NCCP 43021 strains.This discovery revolutionizes influenza vaccine design and delivery;Salmonella-mediated COBRA-HA1 is a highly effective in vivo antigen presentation strategy.This approach can effectively combat seasonal H1N1 influenza strains and potential pandemic outbreaks.
文摘BACKGROUND Patients with diabetes mellitus(DM)are predisposed to an increased risk of infection signifying the importance of vaccination to protect against its potentially severe complications.The Centers for Disease Control and Prevention/Advisory Committee on Immunization Practices(CDC/ACIP)issued immunization recommendations to protect this patient population.AIM To assess the adherence of patients with DM to the CDC/ACIP immunization recommendations in Saudi Arabia and to identify the factors associated with the vaccine adherence rate.METHODS An observational retrospective study conducted in 2023 was used to collect data on the vaccination records from 13 diabetes care centers in Saudi Arabia with 1000 eligible patients in phase I with data collected through chart review and 709 patients in phase II through online survey.RESULTS Among participants,10.01%(n=71)had never received any vaccine,while 85.89%(n=609)received at least one dose of the coronavirus disease 2019(COVID-19)vaccine,and 34.83%(n=247)had received the annual influenza vaccine.Only 2.96%(n=21),2.11%(n=15),and 1.12%(n=8)received herpes zoster,tetanus,diphtheria,and pertussis(Tdap),and human papillomavirus(HPV)vaccines,respectively.For patients with DM in Saudi Arabia,the rate of vaccination for annual influenza and COVID-19 vaccines was higher compared to other vaccinations such as herpes zoster,Tdap,pneumococcal,and HPV.Factors such as vaccine recommendations provided by family physicians or specialists,site of care,income level,DM-related hospitalization history,residency site,hemoglobin A1c(HbA1c)level,and health sector type can significantly influence the vaccination rate in patients with DM.Among non-vaccinated patients with DM,the most reported barriers were lack of knowledge and fear of side effects.This signifies the need for large-scale research in this area to identify additional factors that might facilitate adherence to CDC/ACIP vaccine recommendations in patients with DM.CONCLUSION In Saudi Arabia,patients with DM showed higher vaccination rates for annual influenza and COVID-19 vaccines compared to other vaccinations such as herpes zoster,Tdap,pneumococcal,and HPV.Factors such as vaccine recommendations provided by family physicians or specialists,the site of care,income level,DM-related hospitalization history,residency site,HbA1c level,and health sector type can significantly influence the vaccination rate in patients with DM.
基金supported by grants from the National Clinical Research Center Cancer Fundthe Haihe Laboratory of Synthetic Biology(22HHSWSS00004)。
文摘Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.