Therapeutic Advances in Vaccines and Immunotherapy最新文献

Respiratory syncytial virus (RSV) causes a significant burden of acute respiratory illness across all ages, particularly for infants and older adults. Infants, especially those born prematurely or with underlying health conditions, face a high risk of severe RSV-related lower respiratory tract infections (LRTIs). Globally, RSV contributes to millions of LRTI cases annually, with a disproportionate burden in low- and middle-income countries (LMICs). The RSV virion outer capsule contains glycoproteins G and F which are essential for viral entry into respiratory epithelial cells and represent key targets for therapeutics development. The F-glycoprotein has several highly conserved antigenic sites that have proven useful targets for the development of monoclonal antibodies (mAbs) against RSV. Historically, prevention in infants was limited to the mAb palivizumab, which, despite its efficacy, was costly and inaccessible in many regions. Recent advancements include nirsevimab, a long-acting mAb that has shown substantial efficacy in reducing medically attended RSV-related disease in infants, in phase III clinical trials, early regional and national real-world data. In addition, three new vaccines have been approved: two protein subunit vaccines and a messenger RNA vaccine. The vaccines are all licenced for use in older adults, with one also approved as a maternal vaccine. Promising candidates in development include the mAb clesrovimab, which has an extended half-life and high levels in the nasal epithelial lining and high safety and efficacy profiles in late-stage trials. There are also a wide range of vaccine candidates currently in late-stage clinical trials. These developments signify a major advancement in RSV prevention strategies, offering improved protection for high-risk populations. With the ongoing rollout of the recently licenced vaccines and mAbs internationally, the landscape of RSV care is rapidly changing. We also must ensure these advances reach those in LMICs who need these therapies most.

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide, with HPV and HPV-related diseases representing a substantial disease burden. HPV vaccination has reduced HPV infections and HPV-related diseases; however, there is growing evidence of delayed or refused vaccination due to a lack of trust in vaccines. Understanding the factors that impact vaccine uptake will allow the development and implementation of successful vaccination programmes.

Objectives: This study aimed to evaluate the acceptability of HPV vaccination among adolescents and parents in the United Kingdom (UK).

Design: Systematic review.

Methods: Online databases (Embase, Medline and Cochrane) and grey literature sources were searched to identify publications pertaining to 'adolescents', 'parents', 'vaccine uptake', 'vaccine hesitancy' and 'barriers or facilitators to vaccination'. Searches were limited to English language and articles published specific to the United Kingdom between 2017 and 2023.

Results: Following a review of 152 abstracts, 24 publications met the inclusion criteria. While HPV vaccination is widely accepted in the UK, with coverage reported ⩾80% in peer-reviewed literature, the UK Health Security Agency report that vaccine coverage estimates in England between 2020-2023 remain below 80% and are lower than pre-COVID levels. Several important barriers were identified that may impact vaccine uptake, including system-level (challenges with obtaining consent), psychological/behavioural (perception of HPV risk vs vaccine risks), and sociodemographic factors, with similar factors reported among adolescents and parents.

Conclusion: HPV vaccination coverage remains below pre-COVID levels in the UK and common barriers among adolescents and parents have been identified that must be addressed to improve coverage rates. There is currently limited evidence among adolescent boys to fully evaluate any differences in vaccination coverage, or barriers, compared to girls. More research is required into facilitators to vaccination (especially to address sociodemographic barriers), to identify approaches to tackle the barriers that currently impede HPV vaccination uptake.

Background: Cannabis (CAN) use has risen significantly over the last few decades. CAN has potent immunosuppressive properties, which could antagonize the effect of immunotherapy (IO). The impact of CAN use on clinical cancer outcomes remains unclear.

Objectives: In this study, we evaluated the clinical effect of CAN use on clinical outcomes among patients with solid malignancies receiving IO.

Design: This is a retrospective cohort study of all patients with solid malignancies receiving IO between August 2014 and August 2018.

Methods: Patients were stratified based on CAN use to CAN users and CAN non-users. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and disease control rate (DCR). Univariable and multivariable logistic and Cox regression analyses were performed to compare the outcomes between the two groups, adjusting for covariates.

Results: The records of 106 patients were reviewed, 28 (26%) of whom were CAN users and 78 (74%) were CAN non-users. One patient was excluded. Most CAN users consumed dronabinol (82%). The median follow-up for OS and PFS was 29.2 months. Median OS in the CAN users was 6.7 months compared to 17.3 months in the CAN non-users (HR, 1.78; 95% CI, 1.06-2.97; p = 0.029). The median PFS was 4.8 months in the CAN users compared to 9.7 months in the CAN non-users (HR, 1.74; 95% CI, 1.09-2.79; p = 0.021). DCR was 11% among CAN users and 38% among CAN non-users (OR, 0.23; 95% CI; 0.06-0.68; p = 0.007). An exploratory racial disparity analysis showed that this negative impact of CAN was primarily seen in White patients.

Conclusion: In this single institutional experience, CAN use was associated with worse OS, PFS, and DCR among cancer patients receiving IO. Prospective trials are needed to further study this potential antagonistic interaction between CAN and IO and explore the racial disparities related to CAN exposure.

Respiratory syncytial virus (RSV) causes high worldwide infant mortality, as well as a high disease burden in the elderly. Efforts in vaccine development over the past 60 years have recently delivered three approved vaccines and two monoclonal antibodies (mAbs). Looking back at the eventful history of RSV vaccine development, several factors can be identified that have hampered the developmental pathway, including the occurrence of enhanced RSV disease (ERD) in the first vaccine attempt and the difficulty in characterizing and stabilizing the pre-fusion F protein as a vaccine target. Moreover, the need for large trials to test vaccine efficacy, usually done late in development, and the lack of a correlate of protection (CoP) result in significant uncertainties in RSV vaccine development. The use of controlled human infection models (CHIMs) may provide a solution for some of these problems: through swift, cost-efficient and closely monitored assessment of vaccine safety and efficacy in early clinical phases, vaccines can either 'fail fast' or show results supporting further investments. Moreover, CHIMs facilitate the assessment of disease and could assist in the identification of a CoP supporting late-stage development. Although some factors may affect translatability to real-world vaccine efficacy, CHIMs can support the clinical development pathway in various ways. We advocate for, and demonstrate, a conceptual and rational design of RSV vaccine development. Assessing protective efficacy early on would result in the most cost-efficient pathway and identification of target populations should be done as early as possible. For RSV, elderly individuals and people in low- and middle-income countries are high-impact populations for RSV prevention. While RSV immunization is now available in certain regions, global access is not accomplished yet, and worldwide prevention does not seem within reach. Quick and cost-effective assessments of candidates currently in the pipeline could contribute to future successes in the battle against RSV.

Using artificial intelligence (AI) to enhance chimeric antigen receptor (CAR)-based therapies' design, production, and delivery is a novel and promising approach. This review provides an overview of the current applications and challenges of AI for CAR-based therapies and suggests some directions for future research and development. This paper examines some of the recent advances of AI for CAR-based therapies, for example, using deep learning (DL) to design CARs that target multiple antigens and avoid antigen escape; using natural language processing to extract relevant information from clinical reports and literature; using computer vision to analyze the morphology and phenotype of CAR cells; using reinforcement learning to optimize the dose and schedule of CAR infusion; and using AI to predict the efficacy and toxicity of CAR-based therapies. These applications demonstrate the potential of AI to improve the quality and efficiency of CAR-based therapies and to provide personalized and precise treatments for cancer patients. However, there are also some challenges and limitations of using AI for CAR-based therapies, for example, the lack of high-quality and standardized data; the need for validation and verification of AI models; the risk of bias and error in AI outputs; the ethical, legal, and social issues of using AI for health care; and the possible impact of AI on the human role and responsibility in cancer immunotherapy. It is important to establish a multidisciplinary collaboration among researchers, clinicians, regulators, and patients to address these challenges and to ensure the safe and responsible use of AI for CAR-based therapies.

Background: The risk of neonatal tetanus infection will be reduced when the pregnant woman takes two doses of the maternal tetanus toxoid vaccine. In Ethiopia, however, low immunization coverage levels, mostly due to missed opportunities, are a concern. The study's main objective of the study was to assess tetanus toxoid immunization utilization coverage and associated factors among postnatal mothers in Debre Markos town, Ethiopia.

Materials and methods: A community-based cross-sectional study was conducted among 505 mothers who had given birth in the last 12 months. A two-stage stratified sampling technique was applied, and the The participants were selected using a systematic random sampling technique. Data were entered into EpiData manager version 4.6.0 and analyzed using Statistical Package for Social Science (SPSS) version 25 software. Bivariable and multivariable logistic regression analysis was performed. Adjusted odds ratios (AORs) at 95% CIs were used to identify factors associated with tetanus toxoid immunization utilization.

Results: The total tetanus vaccine intake (TT+2) doses were 71.2% (95% CI: 67.4-76.2). Mothers who attended primary school (AOR: 0.07, 95% CI: (0.01-0.6)), mothers whose husbands had secondary education (AOR: 0.26, 95% CI: (0.08-0.84)), mothers who attended 2-3 times antenatal care (ANC) visit (AOR: 0.05, 95% CI: (0.01-0.3)), good quality service (AOR: 2.8, 95% CI: (1.05-7.5)), appropriate behavior of health workers (AOR: 6.2, 95% CI: (2.2-18.7)), and who visited health extension workers (AOR: 7.6, 95% CI: (2.3-25.3)) were significantly associated with TT vaccine utilization.

Conclusion: Only three out of four pregnant women received the current TT vaccine during their previous pregnancy. The most influencing factors in TT vaccine utilization were the mother and her husband's low educational level, 2-3 times ANC visits during pregnancy, the standard of healthcare service, the healthcare provider's behavior, and the mother's visits with health extension staff.

Background: The COVID-19 pandemic has had an extreme global impact, transforming our daily lives, educational systems, and healthcare systems. Healthcare workers' views on mandatory vaccination and experience with vaccines may play a pivotal role in vaccination rates and public health policy.

Objectives: The purpose of this study is to uncover the perspectives of pharmacy students, at Xavier University of Louisiana, concerning COVID-19 vaccination mandates in educational institutions and healthcare environments, specifically the ethical, legal, and logistical dimensions. Furthermore, it will also assess the varying perceptions of vaccine safety and its impact on herd immunity while analyzing demographic characteristics.

Design: A questionnaire survey.

Methods: This cross-sectional study was conducted among students at Xavier University of Louisiana College of Pharmacy. Data were collected from the students using an online, anonymous questionnaire system named Qualtrics^XM. The survey was distributed to all 291 XULACOP students through email, text message, and GroupMe as a web link or QR code from August 25th to August 31st, 2023. Demographic data collected in the survey included age range, gender, and race/ethnicity. The 16-question survey assessed the students' understanding, opinions, and experiences regarding COVID-19 vaccines and mandates.

Results: The study sample included 151 students, reflecting a 52% response rate. Approximately, half of the study respondents believe the vaccine should be mandatory for the public, which was associated with opinions about students believing COVID-19 vaccines should be mandatory for school admissions were seven times more likely (OR = 7.33) and students believing mandatory vaccination infringes on personal freedom were 26% less likely (OR = 0.26) to support mandatory COVID-19 vaccines for the public(p = 0.000). When analyzing demographic characteristics, there was a significant difference in outcome between Black and non-Black students in their belief about mandatory vaccination for herd immunity (p = 0.016).

Conclusion: The findings of this study indicate that half of the students support making the vaccine mandatory for the public. However, significant concerns about personal freedom and individual rights were expressed by those who opposed this view. Varying pharmacy student opinions among demographic groups on vaccine mandates and understanding the factors influencing these differences can offer valuable insights into public health policy.

Background: The global COVID-19 pandemic, declared in January 2020, necessitated urgent preventive measures, with vaccination as a key strategy. Despite progress in vaccine development and distribution, widespread hesitancy persists, impeding global disease control efforts. This study specifically explores COVID-19 vaccine hesitancy and acceptance among Iranian children with asthma, aiming to understand factors unique to this subgroup.

Method: A cross-sectional investigation was carried out in an allergy clinic in Iran, including a total of 522 asthmatic children between the ages of 5 and 18 years. A comprehensive questionnaire, built upon previous studies, investigated the factors that influence vaccine hesitation and acceptance. Data pertaining to demographics, vaccination status, and factors influencing hesitancy or acceptance were collected.

Results: Among the participants, 27.5% were administered the COVID-19 vaccine. Decisions were greatly influenced by family dynamics, with a notable association between parent and child vaccination. Children's vaccination rates were associated with their age and the frequency of COVID-19 diagnosis among their parents. The primary factors motivating individuals to get vaccinated were safety concerns (67.1%) and a strong belief in the severity of COVID-19 (43.4%). On the other hand, vaccine hesitancy resulted from concerns about potential adverse effects (77%), lack of confidence (28.3%), and a belief that children who had already contracted COVID-19 did not require vaccination (22.5%).

Conclusion: The study highlights COVID-19 vaccine hesitancy and acceptance among asthmatic children in Iran, emphasizing parental decision-making factors. Tailored interventions are required due to the lower vaccination rate in this specific group. Healthcare providers play a vital role in influencing opinions, urging actions against misinformation, enhancing vaccine understanding, and promoting positive attitudes.