Human Vaccines & Immunotherapeutics最新文献

There is a growing political interest in health reforms in Africa, and many countries are choosing national health insurance as their main financing mechanism for universal health coverage. Although vaccination is an essential health service that can influence progress toward universal health coverage, it is not often prioritized by these national health insurance systems. This paper highlights the potential gains of integrating vaccination into the package of health services that is provided through national health insurance and recommends practical policy actions that can enable countries to harness these benefits at population level.

The first-line therapy of metastatic renal cell carcinoma (mRCC) has revolutionized with the approval of immune checkpoint inhibitors (ICIs) in combination with or without tyrosine kinase inhibitors (TKIs). The choice among the many different immuno-combinations (ICI-ICI or ICI-TKI) is challenging due to the lack of predictive factors. The different shapes of the Kaplan-Meier survival curves (e.g. "banana-shaped curves") have raised many questions on the long-term survival benefit. Here, we analyzed the factors that could have impacted the different long-term survival, including the prognostic factors distribution (IMDC score), histological factors (sarcomatoid features, PD-L1 expression), and treatment characteristics (mechanism of action, duration, discontinuation rate). This overview highlights the factors that should be considered in the first-line setting for the patients' therapeutic choice and prognostic assessment. They are also fundamental parameters to examined for head-to-head studies and real-life, large-scale studies.

Background: In low- and middle-income countries where vaccination rates are low, tetanus is still an important threat to public health. Although maternal and neonatal tetanus remains a major global health concern, its magnitude and determinates are not well studied. Therefore, this study aimed to assess the number of tetanus toxoid injections and associated factors among pregnant women in low- and middle-income countries.

Methods: Data from the most recent Demographic and Health Surveys, which covered 60 low- and middle-income countries from 2010 to 2022, was used for secondary data analysis. The study included a total of 118,704 pregnant women. A statistical software package, STATA 14, was used to analyze the data. A negative binomial regression of a cross-sectional study was carried out. Factors associated with the number of tetanus vaccinations were declared significant at a p-value of < 0.05. The incidence rate ratio and confidence interval were used to interpret the results. A model with the smallest Akaike Information Criterion and Bayesian Information Criterion values and the highest log likelihood was considered the best-fit model for this study.

Results: In low- and middle-income countries, 26.0% of pregnant women took at least two doses of the tetanus toxoid vaccine. Factors such as maternal education, primary (IRR = 1.22, 95% CI: 1.17, 1.26), secondary (IRR = 1.19, 95% CI: 1.15, 1.23), higher (IRR = 1.16, 95% CI: 1.12, 1.20), employment (IRR = 1.11, 95% CI: 1.09, 1.13), 1-3 ANC visits (IRR = 2.49, 95% CI: 2.41, 2.57), ≥4 visits (IRR = 2.94, 95% CI: 2.84, 3.03), wealth index (IRR = 1.06; 95% CI: 11.04, 1.08), ≥birth order (IRR = 1.04, 95% CI: 1.02, 1.27), distance to health facility (IRR = 1.02, 95% CI: 1.00, 1.03), and health insurance coverage (IRR = 1.08; 95% CI: 1.06, 1.10) had a significant association with the number of tetanus vaccinations among pregnant women.

Conclusions and recommendations: This study concludes that the number of tetanus toxoid vaccinations among pregnant women in low- and middle-income countries is low. In the negative binomial model, the frequency of tetanus vaccinations has a significant association with maternal employment, educational status, wealth index, antenatal care visits, birth order, distance from a health facility, and health insurance. Therefore, the ministries of health in low and middle-income countries should give attention to those women who had no antenatal care visits and women from poor wealth quantiles while designing policies and strategies.

We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.

To date, thousands of SARS-CoV-2 samples from many vaccine developers have been tested within the CEPI-Centralized Laboratory Network. To convert data from each clinical assay to international standard units, the WHO international standard and the CEPI standard generated by the Medicines and Healthcare products Regulatory Agency were run in multiple facilities to determine the conversion factor for each assay. Reporting results in international units advances global understanding of SARS-CoV-2 immunity and vaccine efficacy, enhancing the quality, reliability, and utility of clinical assay data.

Cancer immunotherapy has emerged as a promising strategy to treat cancer patients. Among the wide range of immunological approaches, cancer vaccines have been investigated to activate and expand tumor-reactive T cells. However, most cancer vaccines have not shown significant clinical benefit as monotherapies. This is likely due to the antigen targets of vaccines, "self" proteins to which there is tolerance, as well as to the immunosuppressive tumor microenvironment. To help circumvent immune tolerance and generate effective immune responses, adjuvants for cancer vaccines are necessary. One representative adjuvant family is Toll-Like receptor (TLR) agonists, synthetic molecules that stimulate TLRs. TLRs are the largest family of pattern recognition receptors (PRRs) that serve as the sensors of pathogens or cellular damage. They recognize conserved foreign molecules from pathogens or internal molecules from cellular damage and propel innate immune responses. When used with vaccines, activation of TLRs signals an innate damage response that can facilitate the development of a strong adaptive immune response against the target antigen. The ability of TLR agonists to modulate innate immune responses has positioned them to serve as adjuvants for vaccines targeting infectious diseases and cancers. This review provides a summary of various TLRs, including their expression patterns, their functions in the immune system, as well as their ligands and synthetic molecules developed as TLR agonists. In addition, it presents a comprehensive overview of recent strategies employing different TLR agonists as adjuvants in cancer vaccine development, both in pre-clinical models and ongoing clinical trials.

Considering the widespread use of COVID-19 vaccines as a preventive measure against the spread of the virus, it's necessary to direct attention to the adverse effects associated with vaccines in a limited group of populations. Multiple evanescent white dot syndrome (MEWDS) following COVID-19 vaccination is a rare adverse reaction associated with COVID-19 vaccines. In this systematic review, we collected 19 articles with 27 patients up to November 1, 2023, summarizing the basic information, clinical manifestations, examinations, treatments, and recoveries of the 27 patients. The 27 enrolled patients (6 males, 21 females) had a median age of 34.1 years (15-71 years old) and were mainly from 5 regions: Asia (8), the Mediterranean region (8), North America (7), Oceania (3) and Brazil (1). Symptoms occurred post-first dose in 9 patients, post-second dose in 14 (1 with symptoms after both), post-third dose in 1, and both post-second and booster doses in 1, while details on 2 cases were not disclosed. Treatments included tapered oral steroids (6), topical steroids (3), tapered prednisone with antiviral drugs and vitamins (1), and valacyclovir and acetazolamide (1), while 16 received no treatment. All patients experienced symptom improvement, and nearly all patients ultimately recovered. Moreover, we summarized possible hypotheses concerning the mechanism of COVID-19 vaccine-associated MEWDS. The findings provide insights into the clinical aspects of COVID-19 vaccine-associated MEWDS. More attention should be given to patients with vaccine-associated MEWDS, and necessary treatment should be provided to patients experiencing a substantial decline in visual acuity to improve their quality of life.

This study aimed to explore the clinical profile and the impact of vaccination status on various health outcomes among COVID-19 patients diagnosed in different phases of the pandemic, during which several variants of concern (VOCs) circulated in South Carolina (SC). The current study included 861,526 adult COVID-19 patients diagnosed between January 2021 and April 2022. We extracted their information about demographic characteristics, vaccination, and clinical outcomes from a statewide electronic health record database. Multiple logistic regression models were used to compare clinical outcomes by vaccination status in different pandemic phases, accounting for key covariates (e.g. historical comorbidities). A reduction in mortality was observed among COVID-19 patients during the whole study period, although there were fluctuations during the Delta and Omicron dominant periods. Compared to non-vaccinated patients, full-vaccinated COVID-19 patients had lower mortality in all dominant variants, including Pre-alpha (adjusted odds ratio [aOR]: 0.33; 95%CI: 0.15-0.72), Alpha (aOR: 0.58; 95%CI: 0.42-0.82), Delta (aOR: 0.28; 95%CI: 0.25-0.31), and Omicron (aOR: 0.29; 95%CI: 0.26-0.33) phases. Regarding hospitalization, full-vaccinated parties showed lower risk of hospitalization than non-vaccinated patients in Delta (aOR: 0.44; 95%CI: 0.41-0.47) and Omicron (aOR: 0.53; 95%CI: 0.50-0.57) dominant periods. The findings demonstrated the protection effect of the COVID-19 vaccines against all VOCs, although some of the full-vaccinated population still have symptoms to varying degrees from COVID-19 disease at different phases of the pandemic.

The contribution of vaccination to global health, especially in low-middle-income countries is one of the achievements in global governance of modern medicine, averting 2-3 million child deaths annually. However, in Nigeria, vaccine-preventable-diseases still account for one-in-eight child deaths before their fifth-year birthday. Nigeria is one of the ten countries where 4.3 million children under five are without complete immunization. Therefore, the goal of this contribution is to shed light on the reasons to set a foundation for future interventions. To conduct focus groups, a simplified quota sampling approach was used to select mothers of children 0-12 months old in four geographical clusters of Nigeria. An interview guide developed from the 5C psychological antecedence model was used (assessing confidence, complacency, calculation, constraints, collective responsibility); two concepts were added that had proved meaningful in previous work (religion and masculinity). The data were analyzed using a meta-aggregation approach. The sample was relatively positive toward vaccination. Still, mothers reported low trust in vaccine safety and the healthcare system (confidence). Yet, they had great interest in seeking additional information (calculation), difficulties in prioritizing vaccination over other equally competing priorities (constraints) and were aware that vaccination translates into overall community wellbeing (collective responsibility). They had a bias toward God as ultimate giver of good health (religion) and their husbands played a dominant role in vaccination decision-making (masculinity). Mothers perceived their children vulnerable to disease outbreaks, hence, motivated vaccination (complacency). The study provided a useful qualitative tool for understanding mothers' vaccination decision-making in low resources settings.

Since the introduction of Haemophilus Influenzae type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important. In Europe, currently three different hexavalent combination vaccines containing Hib conjugates are marketed. In this phase IV, single-blind, randomized, controlled, multi-country study (NCT04535037), we aimed to compare, in a 2 + 1 vaccination schedule, the immunogenicity and safety and show non-inferiority, as well as superiority, of DTPa-HBV-IPV/Hib (Ih group) versus DTaP5-HB-IPV-Hib (Va group) in terms of anti-polyribosylribitol phosphate (PRP) antibody geometric mean concentrations (GMCs) and proportion of participants reaching anti-PRP antibody concentrations greater than or equal to a threshold of 5 µg/mL. One month after the booster vaccination, the anti-PRP antibody GMC ratio (Ih group/Va group) was 0.917 (95% CI: 0.710-1.185), meeting the non-inferiority criteria. The difference in percentage of participants (Ih group - Va group) reaching GMCs ≥5 µg/mL was -6.3% (95% CI: -14.1% to 1.5%), not reaching the predefined non-inferiority threshold. Interestingly, a slightly higher post-booster antibody avidity was observed in the Ih group versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. This study illustrates the different kinetics of the anti-PRP antibody response post-primary and post-booster using the two vaccines containing different Hib conjugates and indicates a potential differential impact of concomitant vaccinations on the anti-PRP responses. The clinical implications of these differences should be further studied.