Safety and efficacy of vaccinations in patients with multiple sclerosis: a systematic review.

OBJECTIVE: The study aims to show the efficacy/effectiveness and safety of vaccinations in patients with multiple sclerosis. MATERIALS AND METHODS: This systematic review was conducted following the guidelines of the Cochrane Collaboration and the meta-analysis of observational studies in epidemiology (MOOSE). RESULTS: At the end of the review process, 133 studies were included; the bibliographic search was conducted on PubMed/Medline and Scopus, combining free text and words. CONCLUSIONS: In general, vaccinations do not seem to aggravate multiple sclerosis (MS) or increase the probability of relapse, particularly for inactivated vaccines and, in general, for the rest of the vaccines. However, it is advisable, especially for vaccines with a live attenuated virus, to carefully evaluate the risks and benefits of these vaccinations; as regards the effectiveness in relation to the drug taken, there is great variability in response. In particular, vaccinations are less effective in patients undergoing therapy with anti-CD20 and S1P modulators. At the same time, a small response is likely to be better than none. Whenever possible, vaccinations should be offered and recommended to patients with multiple sclerosis.

Precision adjuvants for pediatric vaccines.

Elucidating optimal vaccine adjuvants for harnessing age-specific immune pathways to enhance magnitude, breadth, and durability of immunogenicity remains a key gap area in pediatric vaccine design. A better understanding of age-specific adjuvants will inform precision discovery and development of safe and effective vaccines for protecting children from preventable infectious diseases.

Description of vaccination coverage and hesitancy obtained by epidemiological survey of children born in 2017-2018, in Belo Horizonte and Sete Lagoas, Minas Gerais, Brazil.

OBJECTIVE: To describe vaccination coverage and hesitation for the basic children's schedule in Belo Horizonte and Sete Lagoas, Minas Gerais state, Brazil. METHODS: Population-based epidemiological surveys performed from 2020 to 2022, which estimated vaccine coverage by type of immunobiological product and full schedule (valid and ministered doses), according to socioeconomic strata; and reasons for vaccination hesitancy. RESULTS: Overall coverage with valid doses and vaccination hesitancy for at least one vaccine were, respectively, 50.2% (95%CI 44.1;56.2) and 1.6% (95%CI 0.9;2.7), in Belo Horizonte (n = 1,866), and 64.9% (95%CI 56.9;72.1) and 1.0% (95%CI 0.3;2.8), in Sete Lagoas (n = 451), with differences between socioeconomic strata. Fear of severe reactions was the main reason for vaccination hesitancy. CONCLUSION: Coverage was identified as being below recommended levels for most vaccines. Disinformation should be combated in order to avoid vaccination hesitancy. There is a pressing need to recover coverages, considering public health service access and socioeconomic disparities. MAIN RESULTS: Vaccination coverage of children up to 4 years old was 50.2% in Belo Horizonte, and 64.9% in Sete Lagoas. Fear of severe reactions and believing that vaccination against eradicated diseases is unnecessary were the main reasons for vaccination hesitancy. IMPLICATIONS FOR SERVICES: Recovery of high vaccination coverage among children, considering public health service access conditions and socioeconomic inequities. Acting on reasons for hesitancy that can assist in targeting actions. PERSPECTIVES: The multifactorial context of vaccination hesitancy demands the development of health education strategies to raise awareness about child immunization.

Timeliness for vaccination according to the expanded immunization program in children under 6 years of age in Colombia between 2014 and 2019.

The aim was to estimate the vaccination timeliness defined as the proportion of children under 6 years of age who received their immunization in the time range established by the Colombian Expanded Immunization Program (EIP). A retrospective cohort study that collected reports of vaccination opportunities between 2014 and 2019 provided by the Ministry of Health. Age, sex, city, ethnicity, health system affiliation regimen, vaccine applied, and timing of vaccination were considered for the time range under study. A total of 3,370,853 immunized children were included from all regions of the country. More than 80% of children had a timeliness to get most vaccines. The exceptions were yellow fever (17%) and seasonal influenza (42%). No differences in timeliness were found according to geographic region or by health system affiliation regime, but the average timeliness for all vaccines of children of the indigenous population (65.8% ±18.4%) was lower than that of the rest of the population (78·6% ± 19·3%) (p = 0·021). The timeliness for vaccination under the EIP of Colombia is high, with proportions of 72-96%, but intergroup differences were identified, mainly lower timeliness among indigenous people. These findings warrant improvement strategies that would guarantee the immunization of the entire child population.

Significance of VLPs in Vlp-circRNA vaccines: a vaccine candidate or delivery vehicle?

Circular RNAs (circRNAs) are a class of single-stranded RNAs with a closed loop lacking 5' and 3' ends. These circRNAs are translatable and, therefore, have a potential in developing vaccine. CircRNA vaccines have been shown to be more stable, safe, easy to manufacture and scale-up production when compared to mRNA vaccines. However, these vaccines also suffer from several drawbacks such as low circularization efficiency for longer RNA precursor and usage of lipid nano particles (LNPs) in their delivery. LNPs have been shown to require large amounts of RNA due to their indirect delivery from endosome to cytosol. Besides, individual components of LNPs provide reactogenicity. Usage of virus like particles (VLPs) can improve the increased production and targeted delivery of circRNA vaccines and show no reactogenicity. Moreover, VLPs has also been used to produce vaccines against several diseases such as hepatitis C virus (HCV) etc. In this article, we will discuss about the methods used to enhance synthesis or circularization efficiency of circRNA. Moreover, we will also discuss about the significance of VLPs as the delivery vehicle for circRNA and their possible usage as the dual vaccine.

Vaccines and allergy: Back to the right places.

Hypersensitivity reactions represent one of the most common causes of hesitancy for adherence to national vaccination programs. The majority of hypersensitivity reactions after vaccination are mild, and anaphylaxis is reported to be rare, although it remains challenging to estimate the frequency attributed to each single vaccine, either because of the lower number of administered doses of less common vaccines, or the administration of simultaneous vaccine in most of the vaccination programs. Although literature remains scattered, international consensus guides clinicians in identifying patients who might need the administration of vaccines in protected environments due to demonstrated hypersensitivity to vaccine components or adjuvants. Here we provide the current guidance on hypersensitivity reactions to vaccines and on vaccination of children with allergy disorders.

Collecting and reporting adverse events in low-income settings-perspectives from vaccine trials in the Gambia.

BACKGROUND: Despite Africa's significant infectious disease burden, it is underrepresented in global vaccine clinical trials. While this trend is slowly reversing, it is important to recognize and mitigate the challenges that arise when conducting vaccine clinical trials in this environment. These challenges stem from a variety of factors peculiar to the population and may negatively impact adverse event collection and reporting if not properly addressed. METHODS: As a team of clinical researchers working within the MRCG (Medical Research Council Unit The Gambia), we have conducted 12 phase 1 to 3 vaccine trials over the past 10 years. In this article, we discuss the challenges we face and the strategies we have developed to improve the collection and reporting of adverse events in low-income settings. OUTCOME: Healthcare-seeking behaviors in the Gambia are influenced by spiritual and cultural beliefs as well as barriers to accessing orthodox healthcare; participants in trials may resort to non-orthodox care, reducing the accuracy of reported adverse events. To address this, trial eligibility criteria prohibit self-treatment and herbal product use during trials. Instead, round-the-clock care is provided to trial participants, facilitating safety follow-up. Constraints in the healthcare system in the Gambia such as limitations in diagnostic tools limit the specificity of diagnosis when reporting adverse events. To overcome these challenges, the Medical Research Council Unit maintains a Clinical Services Department, offering medical care and diagnostic services to study participants. Sociocultural factors, including low literacy rates and social influences, impact adverse event collection. Solicited adverse events are collected during home visits on paper-based or electronic report forms. Community engagement meetings are held before each study starts to inform community stakeholders about the study and answer any questions they may have. These meetings ensure that influential members of the community understand the purpose of the study and the risks and benefits of participating in the trial. This understanding makes them more likely to support participation within their communities. CONCLUSION: Conducting ethical vaccine clinical trials in resource-limited settings requires strategies to accurately collect and report adverse events. Our experiences from the Gambia offer insights into adverse event collection in these settings.

A New Validated Approach for Identifying Childhood Immunizations in Electronic Health Records in the United Kingdom.

BACKGROUND: Routinely collected electronic health records (EHR) offer a valuable opportunity to carry out research on immunization uptake, effectiveness, and safety, using large and representative samples of the population. In contrast to other drugs, vaccines do not require electronic prescription in many settings, which may lead to ambiguous coding of vaccination status and timing. METHODOLOGY: We propose a comprehensive algorithm to identifying childhood immunizations in routinely collected EHR. In order to deal with ambiguous coding, over-recording, and backdating in EHR, we suggest an approach combining a wide range of medical codes in combination to identify vaccination events and using appropriate wash-out periods and quality checks. We illustrate this approach on a cohort of children born between 2006 and 2014 followed up to the age of five in the Clinical Practice Research Datalink (CPRD) Aurum, a UK primary care dataset of EHR, and validate the results against national estimates of vaccine coverage by NHS Digital and Public Health England. RESULTS: Our algorithm reproduced estimates of vaccination coverage, which are comparable to official national estimates and allows to approximate the age at vaccination. Electronic prescription data only do not cover vaccination events sufficiently. CONCLUSION: Our new proposed method could be used to provide a more accurate estimation of vaccination coverage and timing of vaccination for researchers and policymakers using EHR. As with all observational research using real-world data, it is important that researchers understand the context of the used dataset used and the clinical practice of recording.

Chitosan non-particulate vaccine delivery systems.

Chitosan is an extensively used polymer for drug delivery applications in particulate and non-particulate carriers. Chitosan-based particulate, nano-, and microparticle, carriers have been the most extensively studied for the delivery of therapeutics and vaccines. However, chitosan has also been used in vaccine applications for its adjuvant properties in various hydrogels or as a carrier coating material. The focus of this review will be on the usage of chitosan as a vaccine adjuvant based on its intrinsic immunogenicity; the various forms of chitosan-based non-particulate delivery systems such as thermosensitive hydrogels, microneedles, and conjugates; and the advantages of its role as a coating material for vaccine carriers.

Health and Economic Benefits of Routine Childhood Immunizations in the Era of the Vaccines for Children Program - United States, 1994-2023.

Since 1994, the U.S. Vaccines for Children (VFC) program has covered the cost of vaccines for children whose families might not otherwise be able to afford vaccines. This report assessed and quantified the health benefits and economic impact of routine U.S. childhood immunizations among both VFC-eligible and non-VFC-eligible children born during 1994-2023. Diphtheria and tetanus toxoids and acellular pertussis vaccine; Haemophilus influenzae type b conjugate vaccine; oral and inactivated poliovirus vaccines; measles, mumps, and rubella vaccine; hepatitis B vaccine; varicella vaccine; pneumococcal conjugate vaccine; hepatitis A vaccine; and rotavirus vaccine were included. Averted illnesses and deaths and associated costs over the lifetimes of 30 annual cohorts of children born during 1994-2023 were estimated using established economic models. Net savings were calculated from the payer and societal perspectives. Among approximately 117 million children born during 1994-2023, routine childhood vaccinations will have prevented approximately 508 million lifetime cases of illness, 32 million hospitalizations, and 1,129,000 deaths, at a net savings of $540 billion in direct costs and $2.7 trillion in societal costs. From both payer and societal perspectives, routine childhood vaccinations among children born during 1994-2023 resulted in substantial cost savings. Childhood immunizations continue to provide substantial health and economic benefits, while promoting health equity.

Tailoring biomaterials for vaccine delivery.

Biomaterials are substances that can be injected, implanted, or applied to the surface of tissues in biomedical applications and have the ability to interact with biological systems to initiate therapeutic responses. Biomaterial-based vaccine delivery systems possess robust packaging capabilities, enabling sustained and localized drug release at the target site. Throughout the vaccine delivery process, they can contribute to protecting, stabilizing, and guiding the immunogen while also serving as adjuvants to enhance vaccine efficacy. In this article, we provide a comprehensive review of the contributions of biomaterials to the advancement of vaccine development. We begin by categorizing biomaterial types and properties, detailing their reprocessing strategies, and exploring several common delivery systems, such as polymeric nanoparticles, lipid nanoparticles, hydrogels, and microneedles. Additionally, we investigated how the physicochemical properties and delivery routes of biomaterials influence immune responses. Notably, we delve into the design considerations of biomaterials as vaccine adjuvants, showcasing their application in vaccine development for cancer, acquired immunodeficiency syndrome, influenza, corona virus disease 2019 (COVID-19), tuberculosis, malaria, and hepatitis B. Throughout this review, we highlight successful instances where biomaterials have enhanced vaccine efficacy and discuss the limitations and future directions of biomaterials in vaccine delivery and immunotherapy. This review aims to offer researchers a comprehensive understanding of the application of biomaterials in vaccine development and stimulate further progress in related fields.

National trends in patterns of under-vaccination in early childhood: National Immunization Survey-Child, United States, 2011-2021.

BACKGROUND: The study's objective was to examine national trends in patterns of under-vaccination in the United States. RESEARCH DESIGN AND METHODS: The National Immunization Survey-Child (NIS-Child) is an annual cross-sectional survey that collects provider-verified vaccination records from a large national probability sample of children. Records from the 2011-2021 NIS-Child were used to assess receipt of the combined 7-vaccine series by age 24 months. Based on prior work, patterns indicative of hesitancy included zero vaccines, not starting ≥1 series, and consistent vaccine-limiting. Patterns indicative of practical issues included starting all series but missing doses. Up-to-date (UTD) was defined as receiving all doses in the combined 7-vaccine series. RESULTS: The study population comprised 127,257 children. Over the observation period, patterns indicative of hesitancy significantly decreased (p-trend < 0.0001), patterns indicative of practical issues significantly decreased (p-trend < 0.0001), and UTD significantly increased (p-trend < 0.0001). In 2021, the weighted percentage in each category was as follows: probable hesitancy 6.3% (95% confidence interval [CI] 5.4%, 7.2%), probable practical issues 26.0% (95% CI 24.4%, 27.6%), and UTD 67.7% (95% CI 66.0%, 69.4%). CONCLUSION: Over an 11-year period, vaccination coverage in the United States for the combined 7-vaccine series has improved, with patterns suggestive of practical issues or hesitancy declining.

[Analysis of the operational conditions to preserve immunobiological products in vaccination rooms in Brazil: a mixed study]. / Análise das condições operacionais para conservação de imunobiológicos nas salas de vacinação do Brasil: estudo misto.

This study aimed to analyze the operational conditions to preserve immunobiological products in Brazil. This mixed-method study with a sequential explanatory design was developed in vaccination rooms in several Brazilian regions from 2021 to 2022. Its quantitative stage developed a descriptive cross-sectional study by applying the Immunobiological Conservation Assessment Scale to nursing professionals. Data were analyzed by descriptive statistics. Its qualitative stage developed a descriptive-exploratory study in cold chain instances with the respective technical managers and nursing professionals. The interviews were evaluated by thematic content analysis. The data were combined by connection, and joint-displays and meta-inferences were elaborated. Overall, 280 rooms were analyzed. Most were for exclusive use (79.6%), had polyurethane boxes (77.8%), and kept their equipment away from sunlight/heat (73.5%). Only 27.5% had batteries/generators and 26.5% had other temperature measuring instruments. In total, 60% had refrigerated rooms and 67.6%, air-conditioned rooms. This study found weaknesses associated with geographical conditions, infrastructure, material inputs, human and financial resources, work organization and management, turnover, and training. These findings showed the plurality of the Brazilian cold chain and identified the potentialities and weaknesses related to the structures and work processes in preserving immunobiological products, which require improvement.

Este estudo objetivou analisar as condições operacionais para conservação de imunobiológicos no Brasil. Trata-se de um estudo de método misto com delineamento explanatório sequencial, desenvolvido nas salas de vacinação de distintas regiões brasileiras entre 2021 e 2022. Na etapa quantitativa, desenvolveu-se um estudo transversal descritivo, com a aplicação da Escala de Avaliação da Conservação de Imunobiológicos aos profissionais de enfermagem. Os dados foram analisados por meio de estatística descritiva. Já na etapa qualitativa, desenvolveu-se um estudo descritivo-exploratório nas instâncias da cadeia de frio, com os respectivos responsáveis técnicos e profissionais de enfermagem. Analisou-se as entrevistas por meio da Análise de Conteúdo na Modalidade Temática. Os dados foram combinados mediante conexão, com elaboração de joint-displays e metainferências. Foram analisadas 280 salas, em que grande parte: era de uso exclusivo (79,6%); utilizava caixas de poliuretano (77,8%); e mantinha seus equipamentos distantes da incidência de luz solar/fontes de calor (73,5%). Apenas 27,5% dispunham de baterias/geradores e 26,5% de outros instrumentos de medição de temperatura. Sessenta por cento detinham câmaras refrigeradas e 67,6% ambientes climatizados. Revelaram-se fragilidades associadas a condições geográficas, infraestrutura, insumos materiais, recursos humanos e financeiros, organização e gestão do trabalho, rotatividade e capacitação. Os achados possibilitaram conhecer a pluralidade da cadeia de frio brasileira e permitiram a identificação de potencialidades e fragilidades na conservação de imunobiológicos relacionadas às estruturas e aos processos de trabalho que requerem aprimoramento.

Este estudio tuvo como objetivo analizar las condiciones operativas para la conservación de inmunobiológicos en Brasil. Estudio de método mixto con diseño explicativo secuencial, desarrollado en las salas de vacunación de las distintas regiones brasileñas, entre 2021 y 2022. En la etapa cuantitativa se desarrolló un estudio transversal descriptivo, con la aplicación de la Escala de Evaluación de la Conservación de Inmunobiológicos a los profesionales de enfermería. Los datos fueron analizados mediante estadística descriptiva. En la etapa cualitativa se desarrolló un estudio descriptivo-exploratorio en las instancias de la cadena de frío, con los respectivos responsables técnicos y profesionales de enfermería. Las entrevistas se analizaron por medio del Análisis de Contenido en la Modalidad Temática. Los datos fueron combinados mediante conexión, con elaboración de joint-displays y metainferencias. Se analizaron 280 salas. Gran parte era de uso exclusivo (79,6%); utilizaba cajas de poliuretano (77,8%) y mantenía sus equipos alejados de la incidencia de la luz solar/fuentes de calor (73,5%). Solo el 27,5% disponía de baterías/generadores y el 26,5% de otros instrumentos de medición de temperatura. El 60% tenía cámaras refrigeradas y el 67,6% ambientes climatizados. Se revelaron debilidades asociadas a las condiciones geográficas, la infraestructura, los insumos de materiales, los recursos humanos y financieros, la organización y gestión del trabajo, la rotación y la capacitación. Los hallazgos posibilitaron conocer la pluralidad de la cadena de frío brasileña y permitieron la identificación de potencialidades y debilidades de la conservación de inmunobiológicos relacionadas con las estructuras y los procesos de trabajo que requieren mejoras.

Current Approaches in Postapproval Vaccine Safety Studies Using Real-World Data: A Systematic Review of Published Literature.

PURPOSE: Well-designed observational postmarketing studies using real-world data (RWD) are critical in supporting an evidence base and bolstering public confidence in vaccine safety. This systematic review presents current research methodologies in vaccine safety research in postapproval settings, technological advancements contributing to research resources and capabilities, and their major strengths and limitations. METHODS: A comprehensive search was conducted using PubMed to identify relevant articles published from January 1, 2019, to December 31, 2022. Eligible studies were summarized overall by study design and other study characteristics (eg, country, vaccine studied, types of data source, and study population). An in-depth review of select studies representative of conventional or new designs, analytical approaches, or data collection methods was conducted to summarize current methods in vaccine safety research. FINDINGS: Out of 977 articles screened for inclusion, 135 were reviewed. The review shows that recent advancements in scientific methods, digital technology, and analytic approaches have significantly contributed to postapproval vaccine safety studies using RWD. "Near real-time surveillance" using large datasets (via collaborative or distributed databases) has been used to facilitate rapid signal detection that complements passive surveillance. There was increasing appreciation for self-controlled case-only designs (self-controlled case series and self-controlled risk interval) to assess acute-onset safety outcomes, artificial intelligence, and natural language processing to improve outcome accuracy and study timeliness and emerging artificial intelligence-based analysis to capture adverse events from social media platforms. IMPLICATIONS: Continued development in the area of vaccine safety research methodologies using RWD is warranted. The future of successful vaccine safety research, especially evaluation of rare safety events, is likely to comprise digital technologies including linking RWD networks, machine learning, and advanced analytic methods to generate rapid and robust real-world safety information.

The life cycle of vaccines evaluated by the European Medicines Agency.

BACKGROUND: vaccines are complex products used in healthy populations. They should be carefully regulated, and benefits should clearly outweigh risks. OBJECTIVES: To describe the evidence used to support benefit-risk evaluations of vaccines centrally assessed by the European Medicines Agency (EMA), and to identify if real-world data (RWD) was used throughout the vaccine life cycle. METHODS: Cohort study of vaccines approved in the European Union. Inclusion criteria comprised having ATC code J07 and being centrally approved between 2012 and 2022. We collected data from regulatory documents, study protocols, and, when necessary, from scientific publications. Vaccines were followed from initial approval up to March 2023. RESULTS: We included 31 vaccines addressing 17 therapeutic areas. More than 390 studies were used in the process of initial marketing authorisation (MA) and monitoring, and 174 studies were listed in initial risk management plans. We also identified 93 studies in the EU PAS register. At MA, all vaccines had at least one pivotal trial and 27 vaccines had at least one supportive study. Most pivotal trials were randomized, double-blinded and active-controlled, with immunogenicity endpoints as primary outcome. RWD was used for extension of indications and monitoring of at least 4 vaccines, and the undertaking of RWE studies was foreseen in the RMP of at least 17 vaccines. DISCUSSION: Our study revealed an important reliance on randomized controlled trials with individual-level randomization, and a significant focus on immunogenicity endpoints. The use of RWD in vaccine assessments so far has been restricted to COVID-19, and despite its challenges and limitations, we believe that efforts to expand adoption of RWE in continuous benefit-risk assessments should be made. We further highlight the need to enhance data transparency and reporting standards since heterogeneity among regulatory documents made it difficult to identify all the studies considered in vaccine evaluations.

The broader benefits of vaccines: methodologies for inclusion in economic evaluation.

BACKGROUND: As the societal value of vaccines is increasingly recognized, there is a need to examine methodological approaches that could be used to integrate these various benefits in the economic evaluation of a vaccine. RESEARCH DESIGN AND METHODS: A literature review and two expert panel meetings explored methodologies to value herd immunity, health spillover effects (beyond herd immunity), impact on antimicrobial resistance, productivity, and equity implications of vaccines. RESULTS: The consideration of broader benefits of vaccines in economic evaluation is complicated and necessitates technical expertise. Whereas methodologies to account for herd immunity and work productivity are relatively well established, approaches to investigate equity implications are developing and less frequently applied. Modeling the potential impact on antimicrobial resistance not only depends on the multi-faceted causal relationship between vaccination and resistance but also on data availability. CONCLUSIONS: Different methods are available to value the broad impact of vaccines, and it is important that analysts are aware of their strengths and limitations and justify their choice of method. In the future, we expect that an increasing number of economic evaluations will consider the broader benefits of vaccines as part of their base-case analysis or in sensitivity analyses.

Who is (not) vaccinated? A proposal for a comprehensive immunization information system.

The role of immunization in public health is crucial, offering widespread protection against infectious diseases and underpinning societal well-being. However, achieving optimal vaccination coverage is impeded by vaccine hesitancy, a significant challenge that necessitates comprehensive strategies to understand and mitigate its effects. We propose the integration of Population Health Management principles with Immunization Information Systems (IISs) to address vaccine hesitancy more effectively. Our approach leverages systematic health determinants analysis to identify at-risk populations and tailor interventions, thereby promoting vaccination coverage and public health responses. We call for the development of an enhanced version of the Italian National Vaccination Registry, which aims to facilitate real-time tracking of individuals' vaccination status while improving data accuracy and interoperability among healthcare systems. This registry is designed to overcome current barriers by ensuring robust data protection, addressing cultural and organizational challenges, and integrating behavioral insights to foster informed public health campaigns. Our proposal aligns with the Italian National Vaccination Prevention Plan 2023-2025 and emphasizes proactive, evidence-based strategies to increase vaccination uptake and contrast the spread of vaccine-preventable diseases. The ultimate goal is to establish a data-driven, ethically sound framework that enhances public health outcomes and addresses the complexities of vaccine hesitancy within the Italian context and beyond.

Mapping vaccine names in clinical trials to vaccine ontology using cascaded fine-tuned domain-specific language models.

BACKGROUND: Vaccines have revolutionized public health by providing protection against infectious diseases. They stimulate the immune system and generate memory cells to defend against targeted diseases. Clinical trials evaluate vaccine performance, including dosage, administration routes, and potential side effects. CLINICALTRIALS: gov is a valuable repository of clinical trial information, but the vaccine data in them lacks standardization, leading to challenges in automatic concept mapping, vaccine-related knowledge development, evidence-based decision-making, and vaccine surveillance. RESULTS: In this study, we developed a cascaded framework that capitalized on multiple domain knowledge sources, including clinical trials, the Unified Medical Language System (UMLS), and the Vaccine Ontology (VO), to enhance the performance of domain-specific language models for automated mapping of VO from clinical trials. The Vaccine Ontology (VO) is a community-based ontology that was developed to promote vaccine data standardization, integration, and computer-assisted reasoning. Our methodology involved extracting and annotating data from various sources. We then performed pre-training on the PubMedBERT model, leading to the development of CTPubMedBERT. Subsequently, we enhanced CTPubMedBERT by incorporating SAPBERT, which was pretrained using the UMLS, resulting in CTPubMedBERT + SAPBERT. Further refinement was accomplished through fine-tuning using the Vaccine Ontology corpus and vaccine data from clinical trials, yielding the CTPubMedBERT + SAPBERT + VO model. Finally, we utilized a collection of pre-trained models, along with the weighted rule-based ensemble approach, to normalize the vaccine corpus and improve the accuracy of the process. The ranking process in concept normalization involves prioritizing and ordering potential concepts to identify the most suitable match for a given context. We conducted a ranking of the Top 10 concepts, and our experimental results demonstrate that our proposed cascaded framework consistently outperformed existing effective baselines on vaccine mapping, achieving 71.8% on top 1 candidate's accuracy and 90.0% on top 10 candidate's accuracy. CONCLUSION: This study provides a detailed insight into a cascaded framework of fine-tuned domain-specific language models improving mapping of VO from clinical trials. By effectively leveraging domain-specific information and applying weighted rule-based ensembles of different pre-trained BERT models, our framework can significantly enhance the mapping of VO from clinical trials.