AIM:To investigate the protective efficacy of H2 strain attenuated live hepatitis A vaccines (H2-strain vaccines) in hepatitis A (HA) outbreaks.METHODS:With the permission of their parents, 5551 pre-school and grade 1...AIM:To investigate the protective efficacy of H2 strain attenuated live hepatitis A vaccines (H2-strain vaccines) in hepatitis A (HA) outbreaks.METHODS:With the permission of their parents, 5551 pre-school and grade 1-3 primary school children were inoculated with 1 dose (10(6.5) TCID(50)) of H2 strain vaccines in a nonrandomized, controlled trial conducted in Fucheng County, Hebei Province in May 1997.Another 6485 children in the same grades and compatible in gender and age were enrolled as controls. Epidemiological and serological survey was conducted to evaluate the protective efficacy of the vaccines. ELISA was used to detect serum IgM anti-HAV.RESULTS:HA outbreak started in early May 1998, peaked in the middle of the same month, and lasted about 80 days. Overall 302 HA cases were found, 192(63.58%) were 5-9 years old. One vaccinee and 25 control cases were found to have hepatitis A, which account for 0.28% (1/356) and 5.92% (25/422) of all vaccinees and controls in the 14 villages, respectively. The protective efficacy of vaccines was 95.27% (95% CI: 85.83%-104.72%). In subjects tested for anti-HAV IgM from 13 villages, 1(0.40%) overt and 11(4.06%) asymptomatic HAV cases were found in 271 vaccinees but 21(6.69%) of overt and asymptomatic ones were found in 314 controls.CONCLUSION:H2 strain vaccines were excellent in preventing overt hepatitis A,but not so effective in preventing asymptomatic hepatitis A virus infection.A booster dose might be needed to get permanent reliable immunity.展开更多
Listeria monocytogenes(LM),a Gram-positive facultative intracellular bacterium,can be used as an effective exogenous antigen expression vector in tumor-target therapy.But for successful clinical application,it is nece...Listeria monocytogenes(LM),a Gram-positive facultative intracellular bacterium,can be used as an effective exogenous antigen expression vector in tumor-target therapy.But for successful clinical application,it is necessary to construct attenuated LM stain that is safe yet retains the potency of LM based on the full virulent pathogen.In this study,attenuated LM and recombinants of LM expressing melanoma inhibitory activity(MIA) were constructed successfully.The median lethal dose(LD 50) and invasion efficiency of attenuated LM strains were detected.The recombinants were utilized for immunotherapy of animal model of B16F10 melanoma.The level of MIA mRNA expression in tumor tissue was detected by using real-time polymerase chain reaction(PCR) with specific sequence,meanwhile the anti-tumor immune response was assayed by flow cytometric analysis and enzyme-linked immunosorbent spot(ELISPOT) assay.The results showed the toxicity and invasiveness of attenuated LM were decreased as compared with LM,and attenuated LM expressing MIA,especially the double-genes attenuated LM recombinant,could significantly induce anti-tumor immune response and inhibit tumor growth.This study implicates attenuated LM may be a safer and more effective vector for immunotherapy of melanoma.展开更多
Duck hepatitis B virus(DHBV) shares many basic characteristics with hepatitis B virus(HBV) and is an attractive model for vaccine development. In this study, DHBV DNA vaccines were designed to express envelope and cap...Duck hepatitis B virus(DHBV) shares many basic characteristics with hepatitis B virus(HBV) and is an attractive model for vaccine development. In this study, DHBV DNA vaccines were designed to express envelope and capsid fusion proteins to enhance the breadth of immune response in ducks. Attenuated Salmonella typhimurium(SL7207) was used as a carrier and adjuvant to boost the magnitude of immune response. Based on this strategy, novel DNA vaccines(SL7207-p VAX1-LC and SL7207-p VAX1-SC) were generated. Growth kinetics, genetic stabilities and relative transcription levels of the L, S and C genes introduced by these vaccine strains were measured before inoculation to guarantee safety and efficacy. The relative transcript levels of the CD4 and CD8 T genes and the antibody levels(Ig Y) in ducks receiving the vaccines were higher than those in single gene delivered groups. Additionally, the copy number of covalently closed circular DNA in hepatocytes after DHBV challenge also provided evidence that our fusion vaccines could enhance the protective efficiency against DHBV infection in ducks.展开更多
The primary objective of this study was to evaluation the immune efficacy of native inactivated vaccine against porcine reproductive and respiratory syndrome virus. The experimental design included 60 gilts and 9 boar...The primary objective of this study was to evaluation the immune efficacy of native inactivated vaccine against porcine reproductive and respiratory syndrome virus. The experimental design included 60 gilts and 9 boars equal distribution in two farms free of antibody for PRRSV at the beginning of the experiment for two consecutive months. These gilts and boars were randomly assigned to three treatment groups equally designated as groupsⅠ~Ⅲ. GroupⅠwas inoculated intramuscularly with RespPRRSV/Repro vaccine. Group Ⅱ was inoculated intramuscularly with native multivalent inactivated vaccine. Group Ⅲ was sham-inoculated intramuscularly with saline as control. Gilts and boars were inoculated again at six months intervals during the consecutive 2 years. The neonatal piglets of three groups were inoculated the same vaccine as their parents one week before weaning (piglets were 25 days). Then antibody anti-PRRSV was detected in sera obtained from gilts, boars and piglets. Biological tissue samples were collected from the recently deceased or sacrificed pigs which presented with similar PRRS symptoms. Virus isolation and viral RNA using RT-nPCR were carried through in collected tissue samples, sera and semen. Productive performances of pigs were also evaluated in this project. The results showed all the indexes in groupⅡwere very similar to that of groupⅠexcept the virus isolation and viral RNA detection. Control group had more virus isolates and viral RNA detection than inoculated groups. The rate of piglets surviving, born dead and postnatal deaths and fattening differed significantly (P<(0.05)) between experiment groups and control. This was implied that pigs inoculated with native inactivated vaccine had the similarity immune efficacy to that of pigs inoculated attenuated vaccine. This is the first large-scale to evaluation the immune efficacy of native multivalent inactivated vaccine against PRRSV in field trial. Inoculating native inactivated multivalent vaccine is also an effective measure to prevent PRRS in Shanghai pig farms and this can reduce the risk of vaccine virus shedding because of inoculating the attenuated vaccine.展开更多
Natural killer T(NKT)cells activated with the glycolipid ligandα-galactosylceramide(α-GalCer)stimulate a wide variety of immune cells that enhance vaccine-mediated immune responses.Several studies have used this app...Natural killer T(NKT)cells activated with the glycolipid ligandα-galactosylceramide(α-GalCer)stimulate a wide variety of immune cells that enhance vaccine-mediated immune responses.Several studies have used this approach to adjuvant inactivated and subunit infuenza A virus(IAV)vaccines,including to enhance cross-protective infuenza immunity.However,less is known about whetherα-GalCer can enhance live attenuated infuenza virus(LAIV)vaccines,which usually induce superior heterologous and heterosubtypic immunity compared to non-replicating infuenza vaccines.The current study used the swine infuenza challenge model to assess whetherα-GalCer can enhance cross-protective immune responses elicited by a recombinant H3N2 LAIV vaccine(TX98ΔNS1)encoding a truncated NS1 protein.In one study,weaning pigs were administered the H3N2 TX98ΔNS1 LAIV vaccine with 0,10,50,and 100μg/kg doses ofα-GalCer,and subsequently challenged with a heterologous H3N2 virus.All treatment groups were protected from infection.However,the addition ofα-GalCer appeared to suppress nasal shedding of the LAIV vaccine.In another experiment,pigs vaccinated with the H3N2 LAIV,with or without 50μg/kg ofα-GalCer,were challenged with the heterosubtypic pandemic H1N1 virus.Pigs vaccinated with the LAIV alone generated cross-reactive humoral and cellular responses which blocked virus replication in the airways,and signifcantly decreased virus shedding.On the other hand,combining the vaccine withα-GalCer reduced cross-protective cellular and antibody responses,and resulted in higher virus titers in respiratory tissues.These fndings suggest that:(i)high doses ofα-GalCer impair the replication and nasal shedding of the LAIV vaccine;and(ii)α-GalCer might interfere with heterosubtypic cross-protective immune responses.This research raise concerns that should be considered before trying to use NKT cell agonists as a possible adjuvant approach for LAIV vaccines.展开更多
In this study, thermo-adapted (Ta) PPR vaccines were assessed for their stability at 25, 37, 40, 42 and 45℃ in lyophilized form using two extrinsic stabilizers {lactalbumin hydrolysate-sucrose (LS) and stabilizer...In this study, thermo-adapted (Ta) PPR vaccines were assessed for their stability at 25, 37, 40, 42 and 45℃ in lyophilized form using two extrinsic stabilizers {lactalbumin hydrolysate-sucrose (LS) and stabilizer E} and in reconstituted form with the diluents (1 mol/L MgSO4 or 0.85% NaC1). The lyophilized vaccines showed an expiry period of 24-26 days at 25℃, 7-8 days at 37℃ and 3-4 days at 40℃. LS stabilizer was superior at 42℃ with a shelf-life of 44 h, whereas in stabilizer E, a 40 h shelf-life with a comparable half-life was observed. At 45 ℃, the half-life in stabilizer E was better than LS and lasted for 1 day. Furthermore, the reconstituted vaccine maintained the titre for 48 h both at 4℃ and 25℃ and for 24-30 h at 37℃. As both the stabilizers performed equally well with regard to shelf-life and half-life, the present study suggests LS as stabilizer as a choice for lyophilization with 0.85% NaCldiluent, because it has better performance at higher temperature. These Ta vaccines can be used as alternatives to existing vaccines for the control of the disease in tropical countries as they are effective in avoiding vaccination failure due to the breakdown in cold-chain maintenance, as this vaccine is considerably more stable at ambient temperatures.展开更多
Pseudorabies virus(PRV)is a double-stranded DNA virus with a genome approximating 150 kb in size.PRV contains many non-essential genes that can be replaced with genes encoding heterogenous antigens without affecting v...Pseudorabies virus(PRV)is a double-stranded DNA virus with a genome approximating 150 kb in size.PRV contains many non-essential genes that can be replaced with genes encoding heterogenous antigens without affecting viral propagation.With the ability to induce cellular,humoral and mucosal immune responses in the host,PRV is considered to be an ideal and potential live vector for generation of animal vaccines.In this review,we summarize the advances in attenuated recombinant PRVs and design of PRV-based live vaccines as well as the challenge of vaccine application.展开更多
The coronavirus disease 2019(COVID-19)pandemic has highlighted the importance of developing novel vaccines.An ideal vaccine should trigger an intense immune reaction without causing significant side effects.In this st...The coronavirus disease 2019(COVID-19)pandemic has highlighted the importance of developing novel vaccines.An ideal vaccine should trigger an intense immune reaction without causing significant side effects.In this study we found that substitution of tryptophan located in the cores of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)protein structures with certain smaller amino acids resulted in variants with melting temperatures of 33-37℃.An enzyme activity assay indicated that the proteolytic activity of the main proteinase(3CLpro)decreased sharply when the environmental temperature exceeded the melting temperature,implying that other protein variants may lose most of their functions under the same conditions.This finding suggests that a virus variant containing engineered proteins with melting temperatures of 33-37℃ may only be functional in the upper respiratory tract where the temperature is about 33℃,but will be unable to invade internal organs,which maintain temperatures above 37℃,thus making it possible to construct temperature-sensitive attenuated vaccines.展开更多
The traditional vaccines against hepatitis have been instrumental in reducing the incidence of some types of viral hepatitis;however,the need for cost-effective,easily distributable,and needle-free vaccine alternative...The traditional vaccines against hepatitis have been instrumental in reducing the incidence of some types of viral hepatitis;however,the need for cost-effective,easily distributable,and needle-free vaccine alternatives has led to the exploration of plant-based vaccines.Plant-based techniques offer a promising avenue for producing viral hepatitis vaccines due to their low-cost cultivation,scalability,and the potential for oral administration.This review highlights the successful expression of hepatitis B surface antigens in plants and the subsequent formation of virus-like particles,which have shown immunogenicity in preclinical and clinical trials.The challenges such as achieving sufficient antigen expression levels,ensuring consistent dosing,and navigating regulatory frameworks,are addressed.The review considers the potential of plant-based vaccines to meet the demands of rapid vaccine deployment in response to outbreaks and their role in global immunization strategies,particularly in resource-limited settings.This review underscores the significant strides made in plant molecular farming and the potential of plant-based vaccines to complement existing immunization methods against viral hepatitis.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
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
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
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
Rotaviruses, noroviruses, and astroviruses are responsible for gastroenteritis in children under 5 years old. The objective of our study was to estimate the evolution of prevalence of rotavirus, norovirus and astrovir...Rotaviruses, noroviruses, and astroviruses are responsible for gastroenteritis in children under 5 years old. The objective of our study was to estimate the evolution of prevalence of rotavirus, norovirus and astrovirus infections in children aged 0 to 5 years with gastroenteritis, after the introduction of rotavirus vaccines in Burkina Faso. This cross-sectional study was conducted between January and December 2023, collecting 100 stool samples from children with gastroenteritis at Saint Camille Hospital in Ouagadougou and the Charles De Gaulle University Paediatric Hospital. Noroviruses and astroviruses were detected using multiplex real-time PCR with a Sacace biotechnology detection kit. Data analysis was performed with Stata statistical software, version 16.0. The prevalence of norovirus infections was 14% and astrovirus infections were 9%. Rotavirus infections were found at prevalence of 15%. The age group most affected by norovirus and astrovirus infections was 0 - 12 months, with respective prevalence rates of 73.34% and 55.56%. The most frequently observed clinical signs in children infected with astrovirus were fever (77.78%), diarrhea (55.56%), and vomiting (44.44%). The introduction of rotavirus vaccines has reduced rotavirus-related infections. However, this has not significantly impacted the prevalence of norovirus and astrovirus infections in Burkina Faso.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
We examined the coronavirus classification and evolution through its multiple mutations that have increased its transmissibility rate up to 70% globally, threatening to undermine the promise of a number of emerging va...We examined the coronavirus classification and evolution through its multiple mutations that have increased its transmissibility rate up to 70% globally, threatening to undermine the promise of a number of emerging vaccines that primarily focus on the immune detection of the Spike trimer. The safety and effectiveness of different vaccination methods are evaluated and compared, including the mRNA version, the Adenovirus DNA, Spike protein subunits, the deactivated virus genres, and the live attenuated coronavirus. Mutations have been long considered as random events, or mistakes during the viral RNA replication. Usually, what can go wrong will go wrong;therefore, repeated transformations lead to the extinction of a virus. On the contrary, the aggregate result of over 300,000 Covid-19 variants has expanded its transmissibility and infectiousness. Covid-19 mutations do not degrade the virus;they empower and facilitate its disguise to evade detection. Unlike other coronaviruses, Covid-19 amino acid switches do not reflect the random unfolding of errors that eventually eradicate the virus. Covid-19 appears to use mutations adaptively in the service of its survival and expansion. We cite evidence that Covid-19 inhibits the interferon type I production, compromising adaptive immunity from recognizing the virus. The deleterious consequences of the cytokine storm where the CD8+ killer cells injure the vital organs of the host may well be a Covid-19 manoeuvring to escape exposure. It is probable that evolution has programmed Covid-19 with an adeptness designed to debilitate key systemic defences to secure its subsistence. To date the infectiousness of the Covid-19 pandemic is exponentially increasing, denoting the possibility of an even more dangerously elusive, inconspicuous, and sophisticated version of the disease.展开更多
The purpose of this research review was to examine current scientific literature on COVID-19 vaccine-induced side effects in older adults. We reviewed studies focusing on side effects categorized into cardiologic, imm...The purpose of this research review was to examine current scientific literature on COVID-19 vaccine-induced side effects in older adults. We reviewed studies focusing on side effects categorized into cardiologic, immunologic, neurologic, and ocular groups. Cardiologic side effects included myocarditis, pericarditis, and myocardial infarction. Immunologic conditions examined were anaphylaxis and vaccine-induced immune thrombotic thrombocytopenia. Neurologic side effects included Guillain-Barré syndrome and Bell’s Palsy. Ocular side effects covered ocular swelling, submacular hemorrhage, and corneal graft rejection after keratoplasty and Descemet membrane endothelial keratoplasty. Additionally, less common side effects in older adults were reviewed but found to be statistically rare. Overall, COVID-19 vaccine-induced side effects in elderly populations were rare. We concluded that the vaccine’s efficacy in preventing excess deaths due to COVID-19 is significant, and the risk of these rare side effects does not justify foregoing vaccination in at-risk individuals. Patients at higher risk for these side effects should be informed, and additional considerations should be made by their treating physician. This review aims to increase awareness of rare vaccine-induced side effects to encourage further studies, enhancing understanding of their etiology and prevalence in at-risk older adult populations.展开更多
The advent of RNA therapy,particularly through the development of mRNA cancer vaccines,has ushered in a new era in the field of oncology.This article provides a concise overview of the key principles,recent advancemen...The advent of RNA therapy,particularly through the development of mRNA cancer vaccines,has ushered in a new era in the field of oncology.This article provides a concise overview of the key principles,recent advancements,and potential implications of mRNA cancer vaccines as a groundbreaking modality in cancer treatment.mRNA cancer vaccines represent a revolutionary approach to combatting cancer by leveraging the body’s innate immune system.These vaccines are designed to deliver specific mRNA sequences encoding cancer-associated antigens,prompting the immune system to recognize and mount a targeted response against malignant cells.This personalized and adaptive nature of mRNA vaccines holds immense potential for addressing the heterogeneity of cancer and tailoring treatments to individual patients.Recent breakthroughs in the development of mRNA vaccines,exemplified by the success of COVID-19 vaccines,have accelerated their application in oncology.The mRNA platform’s versatility allows for the rapid adaptation of vaccine candidates to various cancer types,presenting an agile and promising avenue for therapeutic intervention.Clinical trials of mRNA cancer vaccines have demonstrated encouraging results in terms of safety,immunogenicity,and efficacy.Pioneering candidates,such as BioNTech’s BNT111 and Moderna’s mRNA-4157,have exhibited promising outcomes in targeting melanoma and solid tumors,respectively.These successes underscore the potential of mRNA vaccines to elicit robust and durable anti-cancer immune responses.While the field holds great promise,challenges such as manufacturing complexities and cost considerations need to be addressed for widespread adoption.The development of scalable and cost-effective manufacturing processes,along with ongoing clinical research,will be pivotal in realizing the full potential of mRNA cancer vaccines.Overall,mRNA cancer vaccines represent a cutting-edge therapeutic approach that holds the promise of transforming cancer treatment.As research progresses,addressing challenges and refining manufacturing processes will be crucial in advancing these vaccines from clinical trials to mainstream oncology practice,offering new hope for patients in the fight against cancer.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
Nanoparticles are significant for veterinary vaccine development because they are safer and more effective than conventional formulations.One promising area of research involves self-assembled protein nanoparticles(SA...Nanoparticles are significant for veterinary vaccine development because they are safer and more effective than conventional formulations.One promising area of research involves self-assembled protein nanoparticles(SAPNs),which have shown potential for enhancing antigen-presenting cell uptake,B-cell activation,and lymph node trafficking.Numerous nanovaccines have been utilized in veterinary medicine,including natural self-assembled protein nanoparticles,rationally designed self-assembled protein nanoparticles,animal virus-derived nanoparticles,bacteriophagederived nanoparticles,and plant-derived nanoparticles,which will be discussed in this review.SAPN vaccines can produce robust cellular and humoral immune responses and have been shown to protect against various animal infectious diseases.This article attempts to summarize these diverse nanovaccine types and their recent research progress in the field of veterinary medicine.Furthermore,this paper highlights their disadvantages and methods for improving their immunogenicity.展开更多
基金national ninth five-year study program for tackling key scientific problems,No.03-01-01
文摘AIM:To investigate the protective efficacy of H2 strain attenuated live hepatitis A vaccines (H2-strain vaccines) in hepatitis A (HA) outbreaks.METHODS:With the permission of their parents, 5551 pre-school and grade 1-3 primary school children were inoculated with 1 dose (10(6.5) TCID(50)) of H2 strain vaccines in a nonrandomized, controlled trial conducted in Fucheng County, Hebei Province in May 1997.Another 6485 children in the same grades and compatible in gender and age were enrolled as controls. Epidemiological and serological survey was conducted to evaluate the protective efficacy of the vaccines. ELISA was used to detect serum IgM anti-HAV.RESULTS:HA outbreak started in early May 1998, peaked in the middle of the same month, and lasted about 80 days. Overall 302 HA cases were found, 192(63.58%) were 5-9 years old. One vaccinee and 25 control cases were found to have hepatitis A, which account for 0.28% (1/356) and 5.92% (25/422) of all vaccinees and controls in the 14 villages, respectively. The protective efficacy of vaccines was 95.27% (95% CI: 85.83%-104.72%). In subjects tested for anti-HAV IgM from 13 villages, 1(0.40%) overt and 11(4.06%) asymptomatic HAV cases were found in 271 vaccinees but 21(6.69%) of overt and asymptomatic ones were found in 314 controls.CONCLUSION:H2 strain vaccines were excellent in preventing overt hepatitis A,but not so effective in preventing asymptomatic hepatitis A virus infection.A booster dose might be needed to get permanent reliable immunity.
基金supported by grants from the National Natural Science Foundation of China (No. 30600535 and No.30901288)
文摘Listeria monocytogenes(LM),a Gram-positive facultative intracellular bacterium,can be used as an effective exogenous antigen expression vector in tumor-target therapy.But for successful clinical application,it is necessary to construct attenuated LM stain that is safe yet retains the potency of LM based on the full virulent pathogen.In this study,attenuated LM and recombinants of LM expressing melanoma inhibitory activity(MIA) were constructed successfully.The median lethal dose(LD 50) and invasion efficiency of attenuated LM strains were detected.The recombinants were utilized for immunotherapy of animal model of B16F10 melanoma.The level of MIA mRNA expression in tumor tissue was detected by using real-time polymerase chain reaction(PCR) with specific sequence,meanwhile the anti-tumor immune response was assayed by flow cytometric analysis and enzyme-linked immunosorbent spot(ELISPOT) assay.The results showed the toxicity and invasiveness of attenuated LM were decreased as compared with LM,and attenuated LM expressing MIA,especially the double-genes attenuated LM recombinant,could significantly induce anti-tumor immune response and inhibit tumor growth.This study implicates attenuated LM may be a safer and more effective vector for immunotherapy of melanoma.
基金supported by the National Key Technology R&D Program of China(2015BAD12B05)the earmarked fund for China Agricultural Research System(CARS-43-8)+1 种基金the Integration and Demonstration of Key Technologies for Duck Industry in Sichuan Province,China(2014NZ0030)the Sichuan Province Research Programs,China(2014-002)
文摘Duck hepatitis B virus(DHBV) shares many basic characteristics with hepatitis B virus(HBV) and is an attractive model for vaccine development. In this study, DHBV DNA vaccines were designed to express envelope and capsid fusion proteins to enhance the breadth of immune response in ducks. Attenuated Salmonella typhimurium(SL7207) was used as a carrier and adjuvant to boost the magnitude of immune response. Based on this strategy, novel DNA vaccines(SL7207-p VAX1-LC and SL7207-p VAX1-SC) were generated. Growth kinetics, genetic stabilities and relative transcription levels of the L, S and C genes introduced by these vaccine strains were measured before inoculation to guarantee safety and efficacy. The relative transcript levels of the CD4 and CD8 T genes and the antibody levels(Ig Y) in ducks receiving the vaccines were higher than those in single gene delivered groups. Additionally, the copy number of covalently closed circular DNA in hepatocytes after DHBV challenge also provided evidence that our fusion vaccines could enhance the protective efficiency against DHBV infection in ducks.
文摘The primary objective of this study was to evaluation the immune efficacy of native inactivated vaccine against porcine reproductive and respiratory syndrome virus. The experimental design included 60 gilts and 9 boars equal distribution in two farms free of antibody for PRRSV at the beginning of the experiment for two consecutive months. These gilts and boars were randomly assigned to three treatment groups equally designated as groupsⅠ~Ⅲ. GroupⅠwas inoculated intramuscularly with RespPRRSV/Repro vaccine. Group Ⅱ was inoculated intramuscularly with native multivalent inactivated vaccine. Group Ⅲ was sham-inoculated intramuscularly with saline as control. Gilts and boars were inoculated again at six months intervals during the consecutive 2 years. The neonatal piglets of three groups were inoculated the same vaccine as their parents one week before weaning (piglets were 25 days). Then antibody anti-PRRSV was detected in sera obtained from gilts, boars and piglets. Biological tissue samples were collected from the recently deceased or sacrificed pigs which presented with similar PRRS symptoms. Virus isolation and viral RNA using RT-nPCR were carried through in collected tissue samples, sera and semen. Productive performances of pigs were also evaluated in this project. The results showed all the indexes in groupⅡwere very similar to that of groupⅠexcept the virus isolation and viral RNA detection. Control group had more virus isolates and viral RNA detection than inoculated groups. The rate of piglets surviving, born dead and postnatal deaths and fattening differed significantly (P<(0.05)) between experiment groups and control. This was implied that pigs inoculated with native inactivated vaccine had the similarity immune efficacy to that of pigs inoculated attenuated vaccine. This is the first large-scale to evaluation the immune efficacy of native multivalent inactivated vaccine against PRRSV in field trial. Inoculating native inactivated multivalent vaccine is also an effective measure to prevent PRRS in Shanghai pig farms and this can reduce the risk of vaccine virus shedding because of inoculating the attenuated vaccine.
基金funded by the National Institutes of Health grant number HD092286(JPD and JAR)the U.S.Department of Agriculture grant number 2016-09448(JPD)+4 种基金the AMP Core of the Center of Emerging and Zoonotic Infectious Diseases(CEZID)from National Institute of General Medical Sciences(NIGMS)under award number P20GM130448the NIAID supported Centers of Excellence for Infuenza Research and Response(CEIRR,contract number 75N93021C00016the NIAID funded Center of Excellence for Infuenza Research and Surveillance(CEIRS)grant number HHSN272201400006C(JAR)the U.S.Department of Homeland Security grant number DHS2010-ST-061-AG0001(JAR)the Center of Excellence for Emerging and Zoonotic Animal Disease(CEEZAD).
文摘Natural killer T(NKT)cells activated with the glycolipid ligandα-galactosylceramide(α-GalCer)stimulate a wide variety of immune cells that enhance vaccine-mediated immune responses.Several studies have used this approach to adjuvant inactivated and subunit infuenza A virus(IAV)vaccines,including to enhance cross-protective infuenza immunity.However,less is known about whetherα-GalCer can enhance live attenuated infuenza virus(LAIV)vaccines,which usually induce superior heterologous and heterosubtypic immunity compared to non-replicating infuenza vaccines.The current study used the swine infuenza challenge model to assess whetherα-GalCer can enhance cross-protective immune responses elicited by a recombinant H3N2 LAIV vaccine(TX98ΔNS1)encoding a truncated NS1 protein.In one study,weaning pigs were administered the H3N2 TX98ΔNS1 LAIV vaccine with 0,10,50,and 100μg/kg doses ofα-GalCer,and subsequently challenged with a heterologous H3N2 virus.All treatment groups were protected from infection.However,the addition ofα-GalCer appeared to suppress nasal shedding of the LAIV vaccine.In another experiment,pigs vaccinated with the H3N2 LAIV,with or without 50μg/kg ofα-GalCer,were challenged with the heterosubtypic pandemic H1N1 virus.Pigs vaccinated with the LAIV alone generated cross-reactive humoral and cellular responses which blocked virus replication in the airways,and signifcantly decreased virus shedding.On the other hand,combining the vaccine withα-GalCer reduced cross-protective cellular and antibody responses,and resulted in higher virus titers in respiratory tissues.These fndings suggest that:(i)high doses ofα-GalCer impair the replication and nasal shedding of the LAIV vaccine;and(ii)α-GalCer might interfere with heterosubtypic cross-protective immune responses.This research raise concerns that should be considered before trying to use NKT cell agonists as a possible adjuvant approach for LAIV vaccines.
基金Supported by grants from Indian Council of Agricultural Research,Ministry of Agriculture,Government of India,New Delhi,under the Ad-hoc Scheme(F.No.11-3/2007-GA-II and1-1/2007-ASR-IV)
文摘In this study, thermo-adapted (Ta) PPR vaccines were assessed for their stability at 25, 37, 40, 42 and 45℃ in lyophilized form using two extrinsic stabilizers {lactalbumin hydrolysate-sucrose (LS) and stabilizer E} and in reconstituted form with the diluents (1 mol/L MgSO4 or 0.85% NaC1). The lyophilized vaccines showed an expiry period of 24-26 days at 25℃, 7-8 days at 37℃ and 3-4 days at 40℃. LS stabilizer was superior at 42℃ with a shelf-life of 44 h, whereas in stabilizer E, a 40 h shelf-life with a comparable half-life was observed. At 45 ℃, the half-life in stabilizer E was better than LS and lasted for 1 day. Furthermore, the reconstituted vaccine maintained the titre for 48 h both at 4℃ and 25℃ and for 24-30 h at 37℃. As both the stabilizers performed equally well with regard to shelf-life and half-life, the present study suggests LS as stabilizer as a choice for lyophilization with 0.85% NaCldiluent, because it has better performance at higher temperature. These Ta vaccines can be used as alternatives to existing vaccines for the control of the disease in tropical countries as they are effective in avoiding vaccination failure due to the breakdown in cold-chain maintenance, as this vaccine is considerably more stable at ambient temperatures.
基金supported by the Natural Science Foundation of China(grants 32072869,31941015)Shandong Modern Technology System of Agricultural Industry(SDAIT-09-06).
文摘Pseudorabies virus(PRV)is a double-stranded DNA virus with a genome approximating 150 kb in size.PRV contains many non-essential genes that can be replaced with genes encoding heterogenous antigens without affecting viral propagation.With the ability to induce cellular,humoral and mucosal immune responses in the host,PRV is considered to be an ideal and potential live vector for generation of animal vaccines.In this review,we summarize the advances in attenuated recombinant PRVs and design of PRV-based live vaccines as well as the challenge of vaccine application.
基金funding from the Shandong Provincial Key Research and Development Program (2020CXGC011305).
文摘The coronavirus disease 2019(COVID-19)pandemic has highlighted the importance of developing novel vaccines.An ideal vaccine should trigger an intense immune reaction without causing significant side effects.In this study we found that substitution of tryptophan located in the cores of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)protein structures with certain smaller amino acids resulted in variants with melting temperatures of 33-37℃.An enzyme activity assay indicated that the proteolytic activity of the main proteinase(3CLpro)decreased sharply when the environmental temperature exceeded the melting temperature,implying that other protein variants may lose most of their functions under the same conditions.This finding suggests that a virus variant containing engineered proteins with melting temperatures of 33-37℃ may only be functional in the upper respiratory tract where the temperature is about 33℃,but will be unable to invade internal organs,which maintain temperatures above 37℃,thus making it possible to construct temperature-sensitive attenuated vaccines.
文摘The traditional vaccines against hepatitis have been instrumental in reducing the incidence of some types of viral hepatitis;however,the need for cost-effective,easily distributable,and needle-free vaccine alternatives has led to the exploration of plant-based vaccines.Plant-based techniques offer a promising avenue for producing viral hepatitis vaccines due to their low-cost cultivation,scalability,and the potential for oral administration.This review highlights the successful expression of hepatitis B surface antigens in plants and the subsequent formation of virus-like particles,which have shown immunogenicity in preclinical and clinical trials.The challenges such as achieving sufficient antigen expression levels,ensuring consistent dosing,and navigating regulatory frameworks,are addressed.The review considers the potential of plant-based vaccines to meet the demands of rapid vaccine deployment in response to outbreaks and their role in global immunization strategies,particularly in resource-limited settings.This review underscores the significant strides made in plant molecular farming and the potential of plant-based vaccines to complement existing immunization methods against viral hepatitis.
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.
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Rotaviruses, noroviruses, and astroviruses are responsible for gastroenteritis in children under 5 years old. The objective of our study was to estimate the evolution of prevalence of rotavirus, norovirus and astrovirus infections in children aged 0 to 5 years with gastroenteritis, after the introduction of rotavirus vaccines in Burkina Faso. This cross-sectional study was conducted between January and December 2023, collecting 100 stool samples from children with gastroenteritis at Saint Camille Hospital in Ouagadougou and the Charles De Gaulle University Paediatric Hospital. Noroviruses and astroviruses were detected using multiplex real-time PCR with a Sacace biotechnology detection kit. Data analysis was performed with Stata statistical software, version 16.0. The prevalence of norovirus infections was 14% and astrovirus infections were 9%. Rotavirus infections were found at prevalence of 15%. The age group most affected by norovirus and astrovirus infections was 0 - 12 months, with respective prevalence rates of 73.34% and 55.56%. The most frequently observed clinical signs in children infected with astrovirus were fever (77.78%), diarrhea (55.56%), and vomiting (44.44%). The introduction of rotavirus vaccines has reduced rotavirus-related infections. However, this has not significantly impacted the prevalence of norovirus and astrovirus infections in Burkina Faso.
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.
文摘We examined the coronavirus classification and evolution through its multiple mutations that have increased its transmissibility rate up to 70% globally, threatening to undermine the promise of a number of emerging vaccines that primarily focus on the immune detection of the Spike trimer. The safety and effectiveness of different vaccination methods are evaluated and compared, including the mRNA version, the Adenovirus DNA, Spike protein subunits, the deactivated virus genres, and the live attenuated coronavirus. Mutations have been long considered as random events, or mistakes during the viral RNA replication. Usually, what can go wrong will go wrong;therefore, repeated transformations lead to the extinction of a virus. On the contrary, the aggregate result of over 300,000 Covid-19 variants has expanded its transmissibility and infectiousness. Covid-19 mutations do not degrade the virus;they empower and facilitate its disguise to evade detection. Unlike other coronaviruses, Covid-19 amino acid switches do not reflect the random unfolding of errors that eventually eradicate the virus. Covid-19 appears to use mutations adaptively in the service of its survival and expansion. We cite evidence that Covid-19 inhibits the interferon type I production, compromising adaptive immunity from recognizing the virus. The deleterious consequences of the cytokine storm where the CD8+ killer cells injure the vital organs of the host may well be a Covid-19 manoeuvring to escape exposure. It is probable that evolution has programmed Covid-19 with an adeptness designed to debilitate key systemic defences to secure its subsistence. To date the infectiousness of the Covid-19 pandemic is exponentially increasing, denoting the possibility of an even more dangerously elusive, inconspicuous, and sophisticated version of the disease.
文摘The purpose of this research review was to examine current scientific literature on COVID-19 vaccine-induced side effects in older adults. We reviewed studies focusing on side effects categorized into cardiologic, immunologic, neurologic, and ocular groups. Cardiologic side effects included myocarditis, pericarditis, and myocardial infarction. Immunologic conditions examined were anaphylaxis and vaccine-induced immune thrombotic thrombocytopenia. Neurologic side effects included Guillain-Barré syndrome and Bell’s Palsy. Ocular side effects covered ocular swelling, submacular hemorrhage, and corneal graft rejection after keratoplasty and Descemet membrane endothelial keratoplasty. Additionally, less common side effects in older adults were reviewed but found to be statistically rare. Overall, COVID-19 vaccine-induced side effects in elderly populations were rare. We concluded that the vaccine’s efficacy in preventing excess deaths due to COVID-19 is significant, and the risk of these rare side effects does not justify foregoing vaccination in at-risk individuals. Patients at higher risk for these side effects should be informed, and additional considerations should be made by their treating physician. This review aims to increase awareness of rare vaccine-induced side effects to encourage further studies, enhancing understanding of their etiology and prevalence in at-risk older adult populations.
文摘The advent of RNA therapy,particularly through the development of mRNA cancer vaccines,has ushered in a new era in the field of oncology.This article provides a concise overview of the key principles,recent advancements,and potential implications of mRNA cancer vaccines as a groundbreaking modality in cancer treatment.mRNA cancer vaccines represent a revolutionary approach to combatting cancer by leveraging the body’s innate immune system.These vaccines are designed to deliver specific mRNA sequences encoding cancer-associated antigens,prompting the immune system to recognize and mount a targeted response against malignant cells.This personalized and adaptive nature of mRNA vaccines holds immense potential for addressing the heterogeneity of cancer and tailoring treatments to individual patients.Recent breakthroughs in the development of mRNA vaccines,exemplified by the success of COVID-19 vaccines,have accelerated their application in oncology.The mRNA platform’s versatility allows for the rapid adaptation of vaccine candidates to various cancer types,presenting an agile and promising avenue for therapeutic intervention.Clinical trials of mRNA cancer vaccines have demonstrated encouraging results in terms of safety,immunogenicity,and efficacy.Pioneering candidates,such as BioNTech’s BNT111 and Moderna’s mRNA-4157,have exhibited promising outcomes in targeting melanoma and solid tumors,respectively.These successes underscore the potential of mRNA vaccines to elicit robust and durable anti-cancer immune responses.While the field holds great promise,challenges such as manufacturing complexities and cost considerations need to be addressed for widespread adoption.The development of scalable and cost-effective manufacturing processes,along with ongoing clinical research,will be pivotal in realizing the full potential of mRNA cancer vaccines.Overall,mRNA cancer vaccines represent a cutting-edge therapeutic approach that holds the promise of transforming cancer treatment.As research progresses,addressing challenges and refining manufacturing processes will be crucial in advancing these vaccines from clinical trials to mainstream oncology practice,offering new hope for patients in the fight against cancer.
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.
文摘Nanoparticles are significant for veterinary vaccine development because they are safer and more effective than conventional formulations.One promising area of research involves self-assembled protein nanoparticles(SAPNs),which have shown potential for enhancing antigen-presenting cell uptake,B-cell activation,and lymph node trafficking.Numerous nanovaccines have been utilized in veterinary medicine,including natural self-assembled protein nanoparticles,rationally designed self-assembled protein nanoparticles,animal virus-derived nanoparticles,bacteriophagederived nanoparticles,and plant-derived nanoparticles,which will be discussed in this review.SAPN vaccines can produce robust cellular and humoral immune responses and have been shown to protect against various animal infectious diseases.This article attempts to summarize these diverse nanovaccine types and their recent research progress in the field of veterinary medicine.Furthermore,this paper highlights their disadvantages and methods for improving their immunogenicity.