Advances in Zika virus vaccines and therapeutics:A systematic review

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.

Recent advances on vaccines against malaria: A review

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.

Rotavirus, Norovirus and Astrovirus in Children Aged 0 - 5 Years: Evolution of Prevalence over 10 Years (2013-2023) Following the Introduction of Rotavirus Vaccines in Burkina Faso

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.

Neoantigen cancer vaccines:a new star on the horizon

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.

Overcoming neutrophil-induced immunosuppression in postoperative cancer therapy: Combined sialic acid-modified liposomes with scaffold-based vaccines

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.

Plant-based vaccines against viral hepatitis: A panoptic review

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.

Toward innovative veterinary nanoparticle vaccines

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.

Analysis of Public Sentiment regarding COVID-19 Vaccines on the Social Media Platform Reddit

This study undertakes a thorough analysis of the sentiment within the r/Corona-virus subreddit community regarding COVID-19 vaccines on Reddit. We meticulously collected and processed 34,768 comments, spanning from November 20, 2020, to January 17, 2021, using sentiment calculation methods such as TextBlob and Twitter-RoBERTa-Base-sentiment to categorize comments into positive, negative, or neutral sentiments. The methodology involved the use of Count Vectorizer as a vectorization technique and the implementation of advanced ensemble algorithms like XGBoost and Random Forest, achieving an accuracy of approximately 80%. Furthermore, through the Dirichlet latent allocation, we identified 23 distinct reasons for vaccine distrust among negative comments. These findings are crucial for understanding the community’s attitudes towards vaccination and can guide targeted public health messaging. Our study not only provides insights into public opinion during a critical health crisis, but also demonstrates the effectiveness of combining natural language processing tools and ensemble algorithms in sentiment analysis.

An Overview of Quality Management of Therapeutic Vaccines in Clinical Trials in China

Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature research,case study and comparative study were used to analyze the quality management system of clinical trials of therapeutic vaccines.Results and Conclusion From the perspective of the sponsor,investigators and the thirdparty technical service company,the problems such as the low efficiency of clinical trial sample preparation and the lax implementation of the protocol by hospital departments in the quality management of clinical trials of therapeutic vaccines in China were found.Then,the optimization plan for the quality management of clinical trials of therapeutic vaccines is proposed,including optimizing the preparation process of therapeutic vaccines and strengthening the training of hospital department personnel.

Optimization of the Process for Preparing Bivalent Polysaccharide Conjugates to Develop Multivalent Conjugate Vaccines against Streptococcus pneumoniae or Neisseria meningitidis and Comparison with the Corresponding Licensed Vaccines in Animal Models

Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoid(TT)as bivalent conjugates.Methods:Different molecular weights(MWs)of polysaccharides,activating agents and capsular polysaccharide/protein(CP/Pro)ratio that may influence conjugation and immunogenicity were investigated and optimized to prepare the bivalent conjugate bulk.Using the described method and optimized parameters,a 20-valent pneumococcal conjugate vaccine and a bivalent meningococcal vaccine were developed and their effectiveness was compared to that of corresponding licensed vaccines in rabbit or mouse models.Results:The immunogenicity test revealed that polysaccharides with lower MWs were better for Pn1-TT-Pn3 and MenA-TT-MenC,while higher MWs were superior for Pn4-TT-Pn14,Pn6A-TT-Pn6B,Pn7F-TT-Pn23F and Pn8-TT-Pn11A.For activating polysaccharides,1-cyano-4-dimethylaminopyridinium tetrafluoroborate(CDAP)was superior to cyanogen bromide(CNBr),but for Pn1,Pn3 and MenC,N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride(EDAC)was the most suitable option.For Pn6A-TT-Pn6B and Pn8-TT-Pn11A,rabbits immunized with bivalent conjugates with lower CP/Pro ratios showed significantly stronger CP-specific antibody responses,while for Pn4-TT-Pn14,higher CP/Pro ratio was better.Instead of interfering with the respective immunological activity,our bivalent conjugates usually induced higher IgG titers than their monovalent counterparts.Conclusion:The result indicated that the described conjugation technique was feasible and efficacious to prepare glycoconjugate vaccines,laying a solid foundation for developing extended-valent multivalent or combined conjugate vaccines without potentially decreased immune function.

Effectiveness and safety of COVID-19 vaccines in patients with oncological diseases:State-of-the-art

Although the coronavirus disease 2019(COVID-19)pandemic was declared to be no longer“a public health emergency of international concern”with its wide range of clinical manifestations and late complications,severe acute respiratory syndrome coronavirus 2 infection proved to be a serious threat,especially to the elderly and patients with comorbidities.Patients with oncologic diseases are vulnerable to severe infection and death.Indeed,patients with oncohematological diseases have a higher risk of severe COVID-19 and impaired post-vaccination immunity.Unfortunately,cancer patients are usually excluded from vaccine trials and investigations of post-vaccinal immune responses and the effectiveness of the vaccines.We aimed to elucidate to what extent patients with cancer are at increased risk of developing severe COVID-19 and what is their overall case fatality rate.We also present the current concept and evidence on the effectiveness and safety of COVID-19 vaccines,including boosters,in oncology patients.In conclusion,despite the considerably higher mortality in the cancer patient group than the general population,countries with high vaccination rates have demonstrated trends toward improved survival of cancer patients early and late in the pandemic.

Epidemic management in a measles outbreak in 2023,the return of vaccine-preventable diseases:A single center,retrospective observational study

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.

Development of therapeutic cancer vaccines using nanomicellar preparations

Cancer treatment is a multifaceted challenge,and therapeutic vaccines have emerged as a promising approach.The micellar preparation efficiently encapsulates antigen polypeptides and enhances antigen presentation through the major histocompatibility class I pathway,promoting cytotoxic T lymphocyte immune responses.Moreover,it enables codelivery of both antigen and adjuvant to the same target antigen-presenting cells.Combining themicellar vaccine with traditional cancer treatments(such as chemotherapy,radiotherapy,and surgery)has demonstrated improved efficacy in murine tumor models.Overall,the polyethylene glycol-phosphatidylethanolamine micelle-based vaccine presents a promising platformfor cancer therapeutic vaccines.By leveraging the strengths of various treatmentmodalities,this innovative vaccine approach holds the potential to revolutionize cancer therapy and bring new possibilities for cancer patients.

Uptake of Two Doses of HPV Vaccines in Nakuru County, Kenya: A Case of Rongai and Nakuru West Sub-Counties

Background: HPV vaccines were introduced globally as one of the most effective strategies to prevent cervical cancer. HPV vaccines were rolled out in Kenya in 2019 targeting girls aged 10 - 14 years, but the uptake has not been satisfactory. The Purpose of the Study: The aim of the study was to assess the level of HPV uptake among girls aged 10 - 14 years in Rongai and Nakuru West Sub-Counties in Nakuru County. Method: This was a cross-sectional study where data on HPV uptake was retrieved from all the public health facilities located in Rongai and Nakuru West Sub-Counties, Nakuru County, entered into Microsoft Excel then transferred to SPSS version 26 for analysis of HPV vaccine uptake since the year 2019 to June 2022. Data Analysis: Descriptive statistics were used where tables and graphs were generated to represent the percentages and trends of HPV vaccine uptake. Results: The average percentage of HPV uptake in Nakuru West Sub-County since the rollout of vaccination was 17% while that of Rongai Sub-County was 15%. In 2019, HPV 1 uptake was generally low for both Sub-Counties, the results show no HPV 2 vaccines were administered during that year. In 2020, Nakuru West reported an increase in HPV 1 uptake, while Rongai reported a drop in HPV 1 uptake. Both Sub-Counties reported an increase in HPV 2 in 2020 as compared to the previous year. The highest HPV 1 & 2 uptakes were reported in 2021 in both Sub-Counties. The uptake of both HPV 1 & 2 kept increasing subsequently. Conclusion: The overall uptake of HPV vaccines for Doses 1 and 2, in both Rongai and Nakuru West Sub-Counties, is low. However, there has been a consistent increase in uptake of the two doses in the two Sub-Counties since 2019. Therefore, raising public awareness of the importance of HPV vaccination could improve uptake.

Control of highly pathogenic avian influenza through vaccination

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.

Inequity in the global distribution of monkeypox vaccines

Monkeypox(mpox)has been a public health emergency of international concern that emerged in mid-2022 and has spread to 110 countries.The clinical findings of the disease vary according to the seriousness of the cases.Although its case fatality risk has not been high,a significant percentage of patients require hospitalization.In this context,local initiatives were taken to extend the limited supply of vaccines against the disease;however,such measures have not been sufficient to contain the spread of cases and ensure an equitable distribution of health resources.As a result,endemic regions of low-income countries continue to have insufficient access to mpox vaccination.Despite this and considering the global scope of the disease,there is still little discussion in the literature about the difficulties in achieving adequate vaccination coverage rates for the target population of interest.In this article,we briefly discussed general aspects of the disease,including its surveillance,the current global context of challenges for mpox vaccination,and issues on global allocation of health resources as well as proposed related recommendations.

Clinical application of COVID-19 vaccine in liver transplant recipients

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.

Mycobacterium smegmatis enhances shikonin-induced immunogenic cell death—an efficient in situ tumor vaccine strategy

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.

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4t and CD8t T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Enhancement of intranasalmucosal immunization of mucosal vaccines by ultrasonic treatment

The pathogens of most infectious diseases invade the host through mucosal sites,and immunization with mucosal vaccines is the best means of combating these infectious diseases.Oral delivery and nasal delivery are the most common methods of mucosal vaccination.However,the delivery process is inefficient,and mucosal vaccination is ineffective because the vaccine formulation is easily and rapidly removed and has difficulty in crossing the mucosal surface.In this paper,we investigated whether the mucosal immune response could be enhanced by ultrasound facilitation of nasal mucosal delivery of vaccine preparations.For this purpose,we used manganese dioxide(MnO2)as the vaccine carrier/adjuvant,coated with chitosan oligosaccharide(COS)to enhance mucosal adsorption,and further physically adsorbed model antigen ovalbumin(OVA)to construct a nanoparticulate vaccine formulation MnO2@COS@OVA.Ultrasound treatment was found to promote antigen delivery and recruitment of dendritic cells(DCs)and macrophages as well as T-cell infiltration in nasal mucosal tissues through nasal mucosal immunization studies.With ultrasound assistance,MnO2@COS@OVA particles promoted the maturation of DCs in vitro and in vivo and promoted the production of effector memory T cells in vivo and cytokine secretion by splenocytes in vitro.In particular,ultrasound treatment significantly increased the levels of secretory IgA antibodies in the nasal mucosa and genital tract mucosa of experimental mice.In addition,the experimental data showed that the MnO2@COS@OVA particles had good biocompatibility and caused no significant damage to the nasal mucosal and vital organ tissue.These data suggest that ultrasound treatment can promote the induction of efficient immune responses to mucosal vaccines and provide new ideas for the opening and clinical translation of mucosal vaccines.