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.

Biosynthesis and Immunological Evaluation of a Dual-Antigen Nanoconjugate Vaccine Against Brucella melitensis

Brucellosis,caused by Brucella,is one of the most common zoonosis.However,there is still no vaccine for human use.Although some live attenuated vaccines have been approved for animals,the protection effect is not ideal.In this study,we developed a dual-antigen nanoconjugate vaccine containing both polysaccharide and protein antigens against Brucella.First,the antigenic polysaccharide was covalently coupled to the outer membrane protein Omp19 using protein glycan coupling technology,and then it was successfully loaded on a nano-carrier through the SpyTag/SpyCatcher system.After confirming the efficient immune activation and safety performance of the dual-antigen nanoconjugate vaccine,the potent serum antibody response against the two antigens and remarkable protective effect in non-lethal and lethal Brucella infection models were further demonstrated through different routes of administration.These results indicated that the dual-antigen nanoconjugate vaccine enhanced both T helper 1 cell(Th1)and Th2 immune responses and protected mice from Brucella infection.Furthermore,we found that this protective effect was maintained for at least 18 weeks.To our knowledge,this is the first Brucella vaccine bearing diverse antigens,including a protein and polysaccharide,on a single nanoparticle.Thus,we also present an attractive technology for co-delivery of different types of antigens using a strategy applicable to other vaccines against infectious diseases.

Safety of a 13-Valent Pneumococcal Conjugate Vaccine in Elderly Adults Previously Immunized with a 23-Valent Pneumococcal Polysaccharide Vaccine: An Open-Label Trial

An open-label, multicenter study was conducted to describe the safety of the 13-valent pneumococcal conjugate vaccine (PCV13) in 1049 individuals aged ≥68 years, who had previously been immunized with the unconjugated 23-valent pneumococcal polysaccharide vaccine (PPSV23). In addition, the safety profile of PCV13 in this study was compared, in a post-hoc descriptive analysis, to that observed in other elderly populations, who had received PCV13 or PPSV23 as part of other completed studies. Local (56.6%) and systemic reactions (58.4%) were very common, but were mainly mild, and of short duration (mean: 1.3 - 4.6 days). There were no related serious adverse events (AEs) within 1 month after PCV13. 123 days after PCV13 and 94 days after a nonstudy influenza vaccine, a case of transient Guillain-Barré syndrome occurred, which the investigator assessed as possibly related to the vaccination. Reactogenicity observed in this study population was generally similar to that of other elderly study populations with PPSV23-preimmunized adults, and with PPSV23-naive adults. Reactogenicity was less common in this study than that observed in PPSV23-preimmunized adults who were revaccinated with PPSV23 rather than a subsequent dose of PCV13. There were no related serious AEs reported after PCV13 and PPSV23 in these comparator studies. Conclusion: PCV13 may be administered safely to older adults previously immunized with PPSV23. (ClinicalTrials. gov Identifier: NCT00500266)

Persistence of Pleural Effusions and Empyemas after Pneumococcal Conjugate Vaccine Implementation in Uruguay

In Uruguay a post pneumococcal conjugate vaccine implementation surveillance of hospitalized children with pneumonia showed an increase of complicated pneumonias, while uncomplicated pneumonias decreased. Out of 151 pleural effusions, 62 were empyemas requiring drainage, the rest of cases were treated with antibiotics with a favorable outcome. Patient’s vaccinated status varied. Pneumococcal etiology was poorly documented. The few identified sero-types were 1 and 3, a fact that urges PCV13 use for their control.

Potential carrier priming effect in Australian infants after 7-valent pneumococcal conjugate vaccine introduction

AIM:To investigate evidence of clinical protection in infants after one dose of 7-valent pneumococcal conjugate vaccine(7vPCV) owing to carrier priming.METHODS:Using Australian National Notifiable Diseases Surveillance System data,we conducted a descriptive analysis of cases of vaccine type invasive pneumococcal disease(VT-IPD) during "catch-up" years,when 7vPCV was carrier primed by prior administration of DTPa vaccine.We compared the number of VT-IPD cases occurring 2-9 wk after a single dose of 7vPCV(carrier primed),with those < 2 wk post vaccination,when no protection from 7vPCV was expected yet.Further comparison was conducted to compare the occurrence of VT-IPD cases vs non-VT-IPD cases after a single carrier-primed dose of 7vPCV.RESULTS:We found four VT-IPD cases occurring <2 wk after one carrier primed dose of 7vPCV while only one case occurred 2-9 wk later.Upon further comparison with the non-VT-IPD cases that occurred after one carrier primed dose of 7vPCV,two cases were detected within 2 wk,whereas seven occurred within2-9 wk later;suggesting a substantial level of protection from VT-IPD occurring from 2 wk after carrier-primed dose of 7vPCV.CONCLUSION:This data suggest that infants may benefit from just one dose of 7vPCV,likely through enhanced immunity from carrier priming effect.If this is proven,an adjusted 2-dose schedule(where the first dose of PCV is not given until after DTPa) may be sufficient and more cost-effective.

<i>Streptococcus pneumoniae</i>Upper Respiratory Carriage in Costa Rican Children with Otitis Media before the Introduction of the Heptavalent Conjugated Vaccine in the National Immunization Program

Objective: The aim of this study was to analyze the NP/OP S. pneumoniae serotype distribution and potential vaccine coverage in Costa Rican children with Otitis Media (OM) before the introduction of PCV-7 in the National Immunization Program (NIP). Methods: Between 2002 and 2006, NP and OP samples were obtained from 641 children from 6 to 79 months of age, at the time of OM diagnosis. S. pneumoniae serotyping and antimicrobial susceptibility were performed. Results: 386 S. pneumoniae isolates were recovered. The most common S. pneumoniae serotypes (ST) were: ST 6B, ST 14, ST 19F. Penicillin non-susceptibility was observed among 57% of the isolates obtained from children < 24 months of age. 15% strains were multidrug resistant. Potential vaccine coverage was: PCV-7: 60%;PCV-10: 62%;and PCV-13: 76% and against penicillin non-susceptible and multidrug resistant isolates was: PCV-7;59% and 83%, respectively;PCV-10: 60% and 85%, respectively and PCV-13: 74% and 96%, respectively. Conclusions: S. pneumoniae was isolated from the NP and/or OP in the majority (59%) of studied children with OM. At a statistical significant level, only serotype 3 was more frequently isolated among children >24 months of age. Antibiotic non-susceptibility and MDR were significantly higher in children <24 months of age. This study demonstrates that PCV-13 offers the highest potential vaccine coverage and serves to assess the impact of introduction of one of the conjugated vaccines in the NIP in Costa Rica.

Impact of Seven Valent Pneumococcal Conjugate Vaccine on Nasopharyngeal Carriage in Young Children in Okinawa, Japan

In Japan, the heptavalent pneumococcal conjugate vaccine (PCV7) became available in February 2010 and was subsidized by the national funding system from May 2011 in Okinawa, after which it was incorporated into the national immunization practice (NIP) in April 2013 using a 3 + 1 schedule for all infants. We conducted an annual survey in 2012 to determine the effect of PCV7 on nasopharyngeal colonization by pneumococcal serotypes and to analyze the risk factors for colonization in infants. Nasopharyngeal swabs for pneumococcal isolation and serotyping were obtained from infant 2 to 22 months of age before and after PCV7 immunization among 4 clinics in Okinawa, Japan. Between January 2012 and December 2012, nasopharyngeal swabs for bacterial cultures were obtained among 782 infants aged 2 to 22 months old and demographic data was obtained among 725 participant infants. Among the 725 evaluable infants, 193 pneumococcal strains were detected in 180 infants for an overall nasopharyngeal carriage of 24.8%. The main capsular serotypes isolated were 6C (16.1%), 19A (12.4%) and 15B (9.8%). Carriage of PCV7 serotypes accounted for 21.8% (42/193). The result of multivariate data analysis showed the pneumococcal carriage rate of non-PCV7 serotypes was significantly (P < 0.001) high in infant with siblings and daycare attendance. On the other hand, the result of multivariate data analysis showed that carriage rate of PCV7 serotype had only significantly high risk in infant with siblings and did not have a significant risk dependent on age and daycare attendance. Carriage PCV7 serotypes increased in the presence of other siblings, while PCV7 vaccination was shown to eliminate daycare attendance as a risk. The results of this study demonstrates that PCV7 vaccination decrease the overall nasopharyngeal carriage of PCV7 serotypes in vaccinated children including children at risk such as children attending day-care centers.

Effect of 7 and 13-Valent Pneumococcal Conjugate Vaccines Different Number of Doses for Pneumonia Control in 2008 and 2010 Birth Cohort Children

The 7-valent pneumococcal conjugate vaccine (PCV) was introduced in Uruguay in March 2008. In April 2010, it was replaced by PCV13. Surveillance of both vaccines was performed on hospitalized children with consolidated pneumonia. The effect of different number of vaccine doses was evaluated in 2008 and 2010 birth cohorts vaccinated with PCV7 and PCV13 respectively. The study aims to estimate the effects of PCV7 and PCV13 different number of doses on consolidated pneumonia, through the study of hospitalized children from 2008 and 2010 birth cohorts. Vaccination records of every child were available providing precise vaccination data;therefore a new approach was used to estimate PCVs effect. Incidence rate was calculated for each year of the study and for the different number of vaccine doses used each year. Exposure was calculated as person per year and rate ratio values determined the decrease of consolidated pneumonias. This decrease in percentage was estimated as the difference between the incidence with no vaccine and the incidence of every one of the doses. Incidence rate ratio revealed significant values for the three vaccine doses of PCVs for both cohorts. Upon comparing incidences, significant reduction percentages of consolidated pneumonia admissions were found. The reduction percentage of consolidated pneumonia for fully vaccinated (3 doses) patients was 69.3% and 84.6 % for PCV7 and PCV13, respectively. These results confirm that PCV7 and PCV13 are highly effective for reducing pediatric hospitalizations due to consolidated pneumonia, as reported by other national publications and demonstrated by international researchers.

Synthesis, Characterization, and Immunological Properties of LPS-Based Vaccines Composed of O-Polysaccharides Conjugated with Recombinant Exoprotein A from Pseudomonas aeruginosa

Pseudomonas aeruginosa remains one of the major pathogens affecting immunocompromised patients. LPS-based monovalent (MV) and polyvalent (PV) conjugate vaccines were prepared from the most prevalent strains of P. aeruginosa International Antigenic Typing Scheme (IATS) 6, 10, 11 and 20 to evaluate their immunogenicity and protective capacities from infection by the pathogens. Conjugation of the O-polysaccharide (O-PS) antigens of P. aeruginosa strains to the common immunogenic recombinant Exotoxin A (rEPA) supports the multi-antigenic approach for the development of a vaccine that provides cross protection against various strains of the pathogen. The O-PSs were indirectly conjugated through adipic acid dihydrazide (ADH) to rEPA by carbodiimidemediated condensation reaction. Mice were immunized with the conjugates emulsified with monophosphoryl lipid A (MPL) or Freund's adjuvant compared with conjugates without adjuvant, unconjugated mixture of rEPA and O-PS emulsified with MPL, and sterile saline. The MV and PV vaccines emulsified with MPL adjuvant elicited the highest anti-O-PS IgM and IgG antibodies. Immunization of mice with MV vaccines derived from IATS 10, 11, and 20, emulsified with MPL adjuvant provided a high level of protection against the homologous bacterial strain. Similarly, high protection was obtained when mice were immunized using PV and challenged separately with bacterial strains 10, 11, and 20, but lower protection against the IATS 6 strain. Also, high cross protection of MV vaccine derived from O-PS of IATS 10 and 20 was obtained against P. aeruginosa IATS 11 strain. The in vivo protection correlated with the level of anti-O-PS IgG in the mice serum.

Safety Observation Study on Haemophilus Influenza Type B Conjugate Vaccines Injected at Different Sites in Chinese Infants

In the present study, the safety of Hoemophilus influenza type b conjugate vaccines inoculated in the upper arm deltoid and vastus lateralis muscle was evaluated. 680 infants aged 2-5 months and 6-12 months were selected to be the research subjects in whom the Hib conjugate vaccines were inoculated by injection in the upper arm deltoid and vastus lateralis muscle, respectively. The safety analysis indicated that there were no statistic differences in the incidence rates of adverse reactions when the Hib conjugate vaccines were inoculated at different sites. So we concluded that the safety of inoculation injection of Hib conjugate vaccines in vastus lateralis muscle was the same as that inoculated in the upper arm deltoid.

Impact of the Pneumococcal Heptavalent Conjugated Vaccine on <i>Streptococcus pneumoniae</i>Nasopharyngeal Carriage and Antimicrobial Susceptibility in Children 2-5-Year-Old in Beijing, China

Streptococcus pneumoniae is a primary cause of illness and death among children younger than 5 years in China. The heptavalent pneumococcal conjugate vaccine (PCV7) was the only conjugated vaccine (PCV) available in China from 2008 to 2013. This randomized, controlled, open-label study conducted at 46 Beijing clinics involved 3281 healthy 2-5-year-old Chinese children, randomized 1:1 to receive one dose of the S. pneumoniae heptavalent conjugated vaccine (PCV7) (n = 1643) or Haemophilus influenzae type b conjugate vaccine (Hib) (n = 1638). The main objective of this study was to investigate the impact of PCV7 against that of Hib vaccination in the nasopharyngeal S. pneumoniae colonization in healthy Chinese children. Nasopharyngeal (NP) samples for culture, serotyping and antimicrobial susceptibility testing were collected before vaccination and at Day 60 and 180 post-vaccination. A total 3281 children were enrolled in the study. Demographic characteristics were similar among both study groups: 1641 children received PCV7. Before immunization, S. pneumoniae was isolated in 338 and 360 children in the PCV7 (144 PCV7 isolates) and Hib groups (145 PCV7 isolates), respectively. At Day 180, PCV7 vaccination was more effective than Hib vaccination in reduction NP carriage (20.2% [P = 0.052]) and new acquisition (19.0% [P = 0.066]). When reductions in NP carriage and new acquisition of PCV7 VT plus 6A was analyzed, reduction in the PCV7 vaccinated group achieved statistical significance (P = 0.034 and P = 0.042 versus Hib, respectively). NP carriage of NVT increased in both groups (P = 0.305 between study groups at Day 180). PCV7 decreased NP carriage of non-susceptible VT to amoxicillin (P = 0.000), ceftriaxone (P = 0.047) and MDR (P = 0.024) versus Hib. PCV7 vaccination in Chinese children 2 to 5 years of age was more effective than vaccination with Hib in the reduction of S. pneumoniae nasopharyngeal carriage, new acquisition and non-susceptible isolates.

A new approach for development of vaccine against visceral leishmaniasis: Lipophosphoglycan and polyacrylic acid conjugates

Objective: To determine the antileishmanial vaccine effectiveness of lipophosphoglycan(LPG) and polyacrylic acids(PAA) conjugates on in vivo mice models.Methods: LPG molecule was isolated and purified from large-scale Leishmania donovani parasite culture. Protection efficacies of LPG alone, in combination with Freund's adjuvant, in a physical mixture and in conjugate(consisting of various LPG concentrations) with PAA, were comparatively determined by various techniques, such as cultivation with the micro-culture method, assessment of in vitro infection rates of peritoneal macrophages, determination of parasite load in liver with Leishman-Donovan Units, and detection of cytokine responses.Results: Obtained results demonstrated that the highest vaccine-mediated immune protection was provided by LPG-PAA conjugate due to all parameters investigated. According to the Leishman-Donovan Units results, the sharpest decline in parasite load was seen with a ratio of 81.17% when 35 mg LPG containing conjugate was applied. This value was 44.93% for the control group immunized only with LPG. Moreover, decreases in parasite load were 53.37%, 55.2% and 65.8% for the groups immunized with 10 mg LPG containing LPG-PAA conjugate, a physical mixture of the LPG–PAA, and a mixture of LPG + Freund's adjuvant, respectively. Furthermore, cytokine results supported that Th1 mediated protection occurred when mice were immunized with LPG-PAA conjugate.Conclusions: It has been demonstrated in this study that conjugate of LPG and PAA has an antileishmanial vaccine effect against visceral leishmaniasis. In this respect, the present study may lead to new vaccine approaches based on high immunogenic LPG molecule and adjuvant polymers in fighting against Leishmania infection.

Effectiveness of 7-valent pneumococcal conjugate vaccine: A meta-analysis of post-marketing studies

AIM:To investigate the 7-valent pneumococcalconjugate vaccine(PCV7)effectiveness.METHODS:A systematic literature review of studies which evaluated the effectiveness of PCV7 vaccine was performed searching the keyword"heptavalent pneumococcal conjugate vaccine"in PubM ed and Scopus until March 16,2013.The selection of potential eligible articles was done by two researchers independently on the basis of abstract and title and only post-marketing studies were included in the systematic review.Data extraction was carried out by two researchers with respect to invasive pneumococcal diseases due to both all and vaccine serotypes in pre-vaccine and postvaccine periods in children less than 5 years.Results of studies which were considered suitable for meta-analysis were combined by means of relative risk(RR)with95%CI.Vaccine effectiveness was calculated as(1-RR)×100.Heterogeneity was assessed by I2 and a random effects model was used to combine data in the case of heterogeneity.RevM an 5 was used to pool data.RESULTS:On the whole,757 eligible papers were identified from the literature search in PubM ed and Scopus.Of them,62 were finally considered in the systematic review and 38 were included in the meta-analysis.In all post-marketing studies included in the systematic review the incidence of invasive pneumococcal diseases due to vaccine serotypes declined significantly with the exception of few studies showing stability or a slight,but not significant,increase.Furthermore most of studies highlighted also a reduction in the incidence of invasive pneumococcal diseases due to all serotypes.With regards to meta-analysis,a random effects model was used to combine data because of the high heterogeneity.Data combination showed that the effectiveness of PCV7in reducing invasive pneumococcal diseases due to vaccine serotypes and to all serotypes was 84%(95%CI:74%-90%)and 53%(95%CI:46%-59%)respectively.These results are confirmatory with respect to the efficacy of PCV7 against invasive pneumococcal diseasesdue to vaccine serotypes.CONCLUSION:PCV7 implementation determines a significant decrease of invasive pneumococcal diseases.

COVID-19 Vaccine Acceptance and Hesitancy among Pregnant Women: A Knowledge, Attitude, and Perceived Risks Survey in Lusaka, Zambia

Introduction: The coronavirus disease 2019 (COVID-19) is an infectious disease of the respiratory tract caused by SARS-CoV-2. Since its emergence, there have been increased rates of transmission and spread, morbidity and mortality which led to the development of COVID-19 vaccines to address the pandemic. This study assessed acceptance, knowledge, attitude, and perceived risks regarding COVID-19 vaccines among pregnant women attending antenatal care at two First-Level Hospitals in Lusaka, Zambia. Materials and Methods: This was a cross-sectional study that was conducted among 241 pregnant women using a questionnaire from August 2023 to October 2023 in two First-Level Hospitals in Lusaka district, Zambia. The collected data were analyzed using IBM Statistical Package for Social Sciences (SPSS) version 22.0. Statistical analysis was performed using a Chi-square test. The statistical significance was set at a 95% confidence level. Results: Of the 241 participants, 107 (42.7%) were aged between 24 and 34 years. Overall, 64.3% accepted the COVID-19 vaccines, of which 122 (50.6%) were already vaccinated. Further, 203 (84.6%) of the pregnant women had good knowledge, and 199 (82.6%) had positive attitudes towards COVID-19 vaccines. However, 58.5% thought COVID-19 vaccines were not safe and could cause infertility. Alongside this, 70.1% thought that COVID-19 vaccines were harmful during pregnancy. Having good knowledge of COVID-19 vaccines was associated with age (p = 0.049), education status (p = 0.001), and employment status (p = 0.001). Having a positive attitude towards COVID-19 vaccines was associated with education status (p = 0.001) and employment status (p = 0.001). Conclusion: This study found that most pregnant women had good knowledge, and positive attitudes, and the majority accepted the COVID-19 vaccine. Encouragingly, most of the pregnant women who accepted the COVID-19 vaccines were already vaccinated. Most pregnant women thought that COVID-19 vaccines had side effects, were not safe, and could be harmful during pregnancy. Consequently, this could have contributed to the hesitancy to receive a vaccine among some participants. The findings of this study demonstrate the need to provide pregnant women with continuous educational programs on the benefits of vaccinations for themselves and their children.

Penicillin Resistance in Nasopharyngeal Streptococcus pneumoniae among Children with Sickle Cell Disease Immunized with 7-Valent Pneumococcal Conjugate Vaccine

To assess the prevalence, the antimicrobials resistance and to identify risk factors of nasopharyngeal colonization by Streptococcus pneumoniae in children with sickle cell disease (SCD) using prophylactic penicillin and immunized with 7-valent pneumococcal conjugate vaccine. A total of 424 swabs were collected from the nasopharynx in 216 children with SCD and 109 samples from the control group, both from 2 to 60 months age range. Isolation and identification of pneumococci followed standard procedures. Minimum inhibitory concentration (MIC) for penicillin was determined by the E-test method. Prevalence of nasopharyngeal colonization by pneumococci in children with SCD was 17%, and 11% in the control group. The risk factors for increased colonization in children with SCD were the presence of more than five people at home, daycare/school attendance and low prophylaxis compliance. The prevalence of strains with penicillin resistance was 57.5% in patients with SCD and 25% in the control group. Conclusions: Prevalence of pneumococci nasopharyngeal colonization was similar among the study groups. Prophylactic use of penicillin may have increased the prevalence of resistant strains. The vaccine did not decrease the colonization with penicillin resistant strains.

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.

Supramolecular complex glycoconjugate vaccine generates self-enhancement effects for carbohydrate antigen delivery

Targeting delivery of tumor-associated carbohydrate antigen(TACA)-based vaccine to antigen-presenting cells(APCs)mediated by endogenous antibodies can improve the immunogenicity of TACA.However,an essential requirement of this approach is to generate high titers of endogenous antibodies in vivo through pre-immunization,which complicates the immunization procedure and may cause side effects.Herein,we report a new generation of APC-targeting TACA-based supramolecular complex vaccine,assembled by sialyl Thomsen-nouveau-bovine serum albumin-adamantine(sTn-BSA-Ada)and heptavalent rhamnose(Rha)-modifiedβ-cyclodextrin(β-CD)via host-guest interaction.The complex vaccine retained anti-Rha antibodies recruiting capability and facilitated the APCs uptake of the vaccine via the interaction of the Fc-domain with the Fc receptors on APCs.We demonstrate that direct immunization of complex vaccine elicited anti-Rha and anti-sTn specific immune response synchronously,generating a novel self-enhancement effect that can improve the antigen delivery to APCs in high efficacy.The structure-activity relationship(SAR)study proved that complex vaccine 4 with polyethylene glycol 6(PEG 6)linker in host molecule provoked a robust and specific sTn immune response comparable to the pre-immunization approach.The antisera induced by complex vaccine,either through direct immunization or pre-immunization,exhibited equal potency of cytotoxicity against the sTn expression cancer cells.This study provides a general platform for TACA-based vaccines with self-enhancement effects without the need for pre-immunization.

Recent advances and innovations in the design and fabrication of wearable flexible biosensors and human health monitoring systems based on conjugated polymers

Wearable biosensors have received great interest as patient-friendly diagnostic technologies because of their high flexibility and conformability.The growing research and utilization of novel materials in designing wearable biosensors have accelerated the development of point-of-care sensing platforms and implantable biomedical devices in human health care.Among numerous potential materials,conjugated polymers(CPs)are emerging as ideal choices for constructing high-performance wearable biosensors because of their outstanding conductive and mechanical properties.Recently,CPs have been extensively incorporated into various wearable biosensors to monitor a range of target biomolecules.However,fabricating highly reliable CP-based wearable biosensors for practical applications remains a significant challenge,necessitating novel developmental strategies for enhancing the viability of such biosensors.Accordingly,this review aims to provide consolidated scientific evidence by summarizing and evaluating recent studies focused on designing and fabricating CP-based wearable biosensors,thereby facilitating future research.Emphasizing the superior properties and benefits of CPs,this review aims to clarify their potential applicability within this field.Furthermore,the fundamentals and main components of CP-based wearable biosensors and their sensing mechanisms are discussed in detail.The recent advancements in CP nanostructures and hybridizations for improved sensing performance,along with recent innovations in next-generation wearable biosensors are highlighted.CPbased wearable biosensors have been—and will continue to be—an ideal platform for developing effective and user-friendly diagnostic technologies for human health monitoring.

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.