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.

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.

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.

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.

An Analysis of the Impact of Stay-at-Home Measures on the Occurrence of Vaccine Shortages

COVID-19, a contagious respiratory disease, presents immediate and unforeseen challenges to people worldwide. Moreover, its transmission rapidly extends globally due to its viral transmissibility, emergence of novel strains (variants), absence of immunity, and human unawareness. This framework introduces a revised epidemic model, drawing upon mathematical principles. This model incorporates a modified vaccination and lockdown approach to comprehensively depict an epidemics transmission, containment, and decision-making processes within a community. This study aims to provide policymakers with precise information on real-world situations to assist them in making informed decisions about the implementation of lockdown strategies, maintenance variables, and vaccine availability. The suggested model has conducted stability analysis, strength number analysis, and first and second-order derivative analysis of the Lyapunov function and has established the existence and uniqueness of solutions of the proposed models. We examine the combined effects of an effective vaccination campaign and non-pharmaceutical measures such as lockdowns and states of emergency. We rely on the results of this research to assist policymakers in various countries in eradicating the illness by developing more innovative measures to control the outbreak.

A novel live attenuated vaccine candidate protects chickens against subtype B avian metapneumovirus

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.

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.

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.

Socio-Demographic and Economic Factors Associated with Uptake of COVID-19 Vaccine among Pregnant Women at Pumwani Maternity Hospital in Nairobi County, Kenya

Introduction: Pregnant women are a highly vulnerable population for COVID-19 with increased risk of hospitalization, intensive-care unit admission, invasive ventilation support, and mortality. Objective: This study determined the socio-demographic and economic factors associated with the uptake of COVID-19 vaccine among pregnant women utilizing antenatal care services in Pumwani Maternity Hospital, Nairobi County-Kenya. Methods: The study was carried out from 15 June to 23 July 2023. Systematic sampling was used to select 302 women from whom data was collected through face-to-face interviews using a pre-tested semi-structured questionnaire. Data was analyzed using SPSS software in which bivariate and multivariate logistic regression analyses were done at a significance level of p Results: A total of 302 pregnant women participated in the study. Of these, 105 (34.8%) were aged between twenty-six (26) and thirty (30) years. The mean age of the women was 28.60 ± (SD = 5.297). The uptake of the COVID-19 vaccine was 41.1%. The common side effects reported to be associated with the vaccines were fever, headache, joint pain, vomiting and skin rash. Uptake of the COVID-19 vaccine was significantly associated with being married (AOR = 3.65, 95% CI: 0.62 - 1.80, p = 0.001), having a secondary level of education (AOR = 3.78, 95% CI: 0.99 - 2.88, p = 0.001) and being employed (COR = 2.66, 95% CI: 1.31 - 3.06, p = 0.001). Conclusion: COVID-19 vaccination uptake remains low among pregnant women in seeking ANC in Nairobi. The individual factors associated with the uptake of COVID-19 vaccine among pregnant Women at Pumwani maternity hospital in Nairobi County were being married, having secondary level of education and being employed. Integration of the COVID-19 vaccine with other routine vaccinations as per the national immunization program in Kenya and the enhancement of education regarding the safety and efficacy of the COVID-19 vaccine in pregnancy and breastfeeding and economic empowerment of women are recommended.

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.

Antibodies elicited by Newcastle disease virus-vectored H7N9 avian influenza vaccine are functional in activating the complement system

H7N9 subtype avian influenza virus poses a great challenge for poultry industry.Newcastle disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are protective and allow mass administration.Of note,these vaccines elicit undetectable H7N9-specific hemagglutination-inhibition(HI)but high IgG antibodies in chickens.However,the molecular basis and protective mechanism underlying this particular antibody immunity remain unclear.Herein,immunization with an NDV_(vec)H7N9 induced low anti-H7N9 HI and virus neutralization titers but high levels of hemagglutinin(HA)-binding IgG antibodies in chickens.Three residues(S150,G151 and S152)in HA of H7N9 virus were identified as the dominant epitopes recognized by the NDV_(vec)H7N9 immune serum.Passively transferred NDV_(vec)H7N9 immune serum conferred complete protection against H7N9 virus infection in chickens.The NDV_(vec)H7N9 immune serum can mediate a potent lysis of HA-expressing and H7N9 virus-infected cells and significantly suppress H7N9 virus infectivity.These activities of the serum were significantly impaired after heat-inactivation or treatment with complement inhibitor,suggesting the engagement of the complement system.Moreover,mutations in the 150-SGS-152 sites in HA resulted in significant reductions in cell lysis and virus neutralization mediated by the NDV_(vec)H7N9 immune serum,indicating the requirement of antibody-antigen binding for complement activity.Therefore,antibodies induced by the NDV_(vec)H7N9 can activate antibody-dependent complement-mediated lysis of H7N9 virus-infected cells and complement-mediated neutralization of H7N9 virus.Our findings unveiled a novel role of the complement in protection conferred by the NDV_(vec)H7N9,highlighting a potential benefit of engaging the complement system in H7N9 vaccine design.

Factors Associated with HPV Vaccine Uptake among Girls Aged 9 - 14 in the Langue de Barbarie Area of Saint-Louis, Senegal in 2024

Introduction: The HPV vaccine was included in the Expanded Programme on Immunisation in Senegal in 2018. However, vaccination coverage is still low among targeted girls. The aim of this research was to study the factors associated with vaccine uptake among girls aged 9 - 14 years in the Langue de Barbarie area of Saint-Louis, Senegal. Methodology: This was a descriptive and analytical cross-sectional study. The sample size was calculated using the Schwartz formula and distributed proportionally to the size of the population in the neighborhoods. Data were collected from 2nd to 19th January 2024 from mothers or guardians of girls aged 9 to 14 using anonymous questionnaires configured on tablets with Survey 123 software and analysed using R software. Results: A total of 799 people were interviewed. The average age of the respondents was 35.67 years, with a standard deviation of 7.08 and a range of 17 and 49 years. Reported vaccination coverage was 41.9%. Factors positively correlated with vaccination included: attendance at primary school or daara (OR = 2.50 [CI: 1.43 - 4.48] and OR = 2.05 [CI: 1.09 - 3.94]), information about vaccination (OR = 6.64 [CI: 4.59 - 9.72]), history of cervical cancer screening among mothers or guardians (OR = 6.64 [CI: 4.59 - 9.72]). Conclusion: Identifying the factors associated with HPV vaccination is necessary to assess and improve the vaccination strategy in order to improve vaccination coverage among targeted girls.

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.

Prevention and Nursing of Adverse Reactions of Novel Coronavirus Inactivated Vaccine (Vero Cells)

Objective:To discuss and analyze the causes of adverse reactions caused by the inactivated novel coronavirus vaccine(Vero cells),and to propose methods of prevention and care.Methods:A questionnaire was used to randomly select 229 adults who were vaccinated with the inactivated novel coronavirus vaccine(Vero cells)at Xi’an People’s Hospital(Xi’an Fourth Hospital).The adverse reactions were statistically analyzed.Results:Among the 229 adults vaccinated with the inactivated novel coronavirus vaccine(Vero cells),30 experienced vaccination reactions.The main reaction was local induration at the inoculation site,and dizziness was the primary systemic symptom.Conclusion:To reduce the incidence of adverse reactions to the inactivated novel coronavirus vaccine(Vero cells),it is necessary to effectively evaluate the health status of adults before vaccination,select the correct vaccination site,and strictly implement the rules of 3-inspections,7-checks,and 1-verification.Standardizing the operation process and providing thorough health education after vaccination can effectively reduce the occurrence of adverse reactions.

mRNA vaccine:a new generation of technology revolution in biomedicine

Vaccination has played a crucial role in combating infectious diseases for human and has made significant contributions to global public health.Successful vaccination has eradicated many life-threatening diseases,such as smallpox and polio[1].The World Health Organization estimates that vaccines can prevent 2–3 million deaths from tetanus,pertussis,influenza,and measles annually.

Analysis of Epidemiological Characteristics of Varicella Before and After the Implementation of the Two-dose Varicella Vaccine Immunization Program in Banan District of Chongqing City

Objective:To explore the changes in the epidemiological characteristics of varicella before and after implementing the two-dose varicella vaccine(VarV)immunization program in the Banan District of Chongqing and to provide a reference for future epidemic prevention and control.Methods:The data of reported varicella cases in Banan District from 2014 to 2023 were collected and analyzed using the China Disease Prevention and Control Information System.Descriptive epidemiological methods were employed to assess the changes in the reported incidence of varicella before(2014-2018)and after(2019-2023)the implementation of the two-dose VarV immunization program.Results:The average annual reported incidence rate of varicella in Banan District from 2014 to 2023 was 81.53 per 100,000.From 2014 to 2018,the reported incidence rate showed an upward trend year by year(trend x2=223.96,P<0.05).However,the reported incidence rate decreased from 2019 to 2023(trend x?=189.51,P<0.05).Before and after the adjustment of the immunization program,the reported incidence rate for the 5-9 years old group was 774.62 per 100,000 and 476.98 per 100,000,respectively,with a statistically significant difference(x2=161.26,P<0.05).The onset of varicella showed a bimodal distribution,with peak incidence periods in May-June and October-December.From 2014 to 2023,a total of 155,181 doses of VarV were administered in Banan District.The estimated annual vaccination rate for the first varicella vaccine(VarV1)from 2019 to 2023 was 86.28%,and for the second dose(VarV2)was 59.18%.The primary vaccination targets were the 5-9-year-old group,accounting for 64.21%.Conclusion:After implementing the two-dose VarV immunization program in Banan District,the vaccination rate increased yearly,and the reported incidence of varicella showed a downward trend.The incidence rate of varicella in children aged 5-9 years reduced significantly,but the overall downward trend for the entire population was not as pronounced.Therefore,it is necessary to increase the vaccination rate of VarV2.

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.

A Case of Investigation and Diagnosis of Immune Thrombocytopenic Purpura After Vaccination of COVID-19 Inactivated Vaccine

Objective:Analyze the relationship between inoculating one case of the COVID-19 inactivated vaccine(Vero cell)and immune thrombocytopenic purpura to provide a reference for the standardized handling of adverse events following immunization.Methods:According to the"National Monitoring Program for Suspected Adverse Reactions to Vaccinations,"an on-site investigation,data collection and analysis,expert group diagnosis,and medical association assessment were conducted on a case of immune thrombocytopenic purpura in District A of Chongqing after vaccination with the inactivated COVID-19 vaccine.The assessment report was delivered to the three relevant parties,the case was reviewed,and the experience was summarized.Results:The investigation and diagnosis by the district-level vaccination abnormal reaction expert group concluded that the disease that occurred after vaccination with the COVID-19 inactivated vaccine was secondary immune thrombocytopenic purpura,an abnormal reaction to the vaccination.The medical damage was classified as Level II Grade B.The vaccine production enterprise raised objections to this conclusion.After re-assessment by the municipal-level medical association,the conclusion was consistent with that of the district-level medical association.The vaccine production enterprise did not raise any further objections.Conclusion:Through active collaboration among district and municipal-level medical associations,disease control institutions,and vaccination units,the recipients have been promptly and effectively treated,providing financial support for their subsequent treatment and safeguarding their rights.The investigation and disposal procedures for adverse events following immunization in Chongqing are clear,and the mechanism is sound.It is necessary to continue strengthening the monitoring of adverse events following immunization according to the existing plan and to ensure timely and standardized handling.Simultaneously,it is crucial to strengthen vaccine management and vaccination management.

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.