Vaccines最新文献

Streptococcus pneumoniae contributes significantly to morbidity, mortality, and healthcare costs worldwide due to severe Invasive Pneumococcal Disease (IPD), particularly among young children and vulnerable populations. This review critically examines the current state of pneumococcal disease epidemiology, the evolution of vaccine strategies, and persistent challenges to achieve global control of the disease. The implementation of Pneumococcal Conjugate Vaccines (PCVs) has yielded substantial public health gains, establishing herd protection and sharply reducing vaccine-type IPD incidence. However, this success has been fundamentally challenged by serotype replacement, where non-vaccine serotypes have subsequently emerged to cause a significant proportion of the residual disease burden. This epidemiological shift has necessitated the development and deployment of higher-valency PCVs (PCV15, PCV20, and PCV21) to expand serotype coverage. Furthermore, optimal protection requires personalized strategies for high-risk cohorts where vaccine effectiveness can be compromised. In this context, the review details how pneumococcal vaccination-and particularly PPSV23-serves as an indispensable diagnostic tool to evaluate a broad spectrum of Inborn Errors of Immunity (IEI) and in particular humoral defects. Diagnostic challenges are strained by non-standardized assays and the limited panel of unique serotypes available for testing in the PCV era. The scientific priority is now the development of universal protein-based vaccines, to provide protection against all serotypes and non-encapsulated strains by targeting conserved virulence factors. This integrated approach, combining expanded PCV coverage with novel vaccine technology, is essential to mitigate the ongoing public health burden of pneumococcal disease.

Objective: This study aimed to assess COVID-19 vaccine effectiveness against death (VE), controlling for healthy vaccinee bias.

Methods: We link all adult deaths through year-end 2022 in the State of Indiana, U.S.A., to vaccination records and identify which deceased received primary vaccination (measured as either one or two initial doses) and which received one or two booster doses. We measure COVID-19 mortality with the COVID Excess Mortality Percentage (CEMP). CEMP is calculated, for a group defined by various characteristics (age, sex, time period), as COVID-19 deaths divided by non-COVID natural deaths. The CEMP outcome measure accounts for healthy vaccinee bias by using non-COVID natural mortality to control for differences in population health.

Results: We find a large healthy vaccinee bias. Controlling for this bias, we find substantial VE for primary vaccination and the first booster dose during the first five vaccine-available calendar quarters, from 1Q2021 through 1Q2022 (end of Omicron infection wave). However, over 2Q-4Q2022, we find no evidence for primary-vaccination VE, and find moderate but statistically insignificant booster VE, which largely wanes by 4Q2022.

Conclusions: It is known that by 2Q2022, most people had natural immunity from prior COVID-19 infection. Thus, our results for 2Q-4Q2022 largely reflect comparing hybrid (infection plus vaccination) immunity to infection-only immunity. In this period, we find negligible mortality benefit from primary vaccination, and moderate but waning benefit from a booster dose.

Policy implications: Controlling for healthy vaccinee bias is crucial when estimating VE. We found limited VE against COVID-19 mortality over 2Q-4Q2022, but lacked data for more recent periods.

Background/Objectives: Paediatricians' recommendations influence parental decisions to vaccinate their children. On 19 January 2022, the World Health Organization authorized the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) under Emergency Use Listing for children under 12 years as a measure to mitigate disease spread and direct protection for children with underlying conditions. We assessed knowledge, attitudes, and practices (KAP) of Palestinian paediatricians regarding COVID-19 vaccination for children under 12 years and identified factors affecting support for vaccination. Methods: From 1 October to 8 November 2023, we surveyed paediatricians across the West Bank using structured telephone interviews. We collected data on sociodemographic characteristics and KAP regarding COVID-19 vaccination and calculated KAP scores from eight, nine, and nine items, respectively, with total scores categorized as poor/moderate/good. We performed bivariable and multivariable analyses to identify factors associated with paediatricians supporting COVID-19 vaccination for children under 12 years. Results: Of the 367 eligible paediatricians, 323 (88%) responded; the median age was 51 years (range: 28-70); 27% supported COVID-19 vaccination for children. Mean scores for knowledge (range 0-8), attitude (0-9), and practice (0-9) were 3.0 ± 2.1, 3.9 ± 2.4, and 4.0 ± 1.7, respectively. The mean overall KAP score (0-26) was 11 ± 4.8. Safety and efficacy concerns and lack of long-term data were the main reasons for hesitancy. Higher knowledge scores (PR = 1.8, 95% CI: 1.3-2.5, p = 0.001) and positive attitudes (PR = 1.6, 95% CI: 1.1-2.3, p = 0.01) were significantly associated with paediatricians' support for vaccination. After adjustment for other factors, participants with regular continuing medical education attendance (aPR = 1.4, 95% CI: 1.0-2.6, p = 0.045), trusting WHO recommendations (aPR = 3.1, 95% CI: 1.4-7.8, p = 0.047), having a positive attitude score (aPR = 1.3, 95% CI: 0.4-4.4, p = 0.041), and a good total KAP score (aPR = 1.1, 95% CI: 1.0-1.2, p = 0.044) supported COVID-19 vaccination for children. Conclusions: Support for COVID-19 vaccination among Palestinian paediatricians was low, associated with their knowledge, attitudes, and trust in health authorities. The revised WHO recommendations from 10 November 2023, decreasing the priority of vaccinating healthy children, could influence the opinion of paediatricians. However, the low support for COVID-19 vaccinations could affect the performance of other vaccination programmes and should be carefully addressed through targeted education.

Four years after the acute COVID-19 emergency, respiratory viruses circulate in overlapping seasonal patterns that repeatedly test surveillance systems and healthcare capacity [...].

Background: Adjuvants enhance the immune response to antigens incorporated in vaccine formulations. Given that the majority of infectious agents enter the body through mucosal surfaces, efficacious vaccines must generate protective immunity at these sites, which serve as the first line of defense. There is a need for mucosal adjuvants; hence, we explored the potential of repurposing existing drugs with established safety profiles in humans. Polymyxins are a class of clinically used antibiotics. They are cationic peptides and mast cell activators, which are a novel class of vaccination adjuvants. The goal was to assess the adjuvant properties of Polymyxin B microparticles in combination with vaccine candidates previously developed in our laboratory, such as microparticulate gonorrhea, influenza, measles, Zika, and canine coronavirus vaccines, and to compare their performance with FDA-licensed adjuvants, such as MF59 and Alum.

Methods: Polymyxin microparticles were formulated using a double emulsion method, and the toxicity profile and autophagosome generation of Polymyxin B microparticles were assessed. The immunogenic potential of Polymyxin B in these vaccines was studied using multiple parameters such as nitric oxide release using Griess assay and immune profiling using flow cytometry for markers such as MHC I, MHC II, CD40, and CD80.

Results: Polymyxin B microparticles were found to be non-cytotoxic to dendritic cells up to 500 μg/mL. Polymyxin B promoted autophagosome formation and nitric oxide release, and showed the upregulation of MHC I, MHC II, CD80, and CD40 pathways.

Conclusions: The adjuvant activity of Polymyxin B across various vaccine platforms is significantly comparable to FDA-approved adjuvants, which is a critical requirement for generating T cell responses such as helper T cell and cytotoxic CD8+ T cell responses.

Background/Objectives: Health literacy and vaccine literacy influence vaccine uptake behavior. Ensuring that people in rural communities are knowledgeable about vaccines can be an important tool in increasing influenza vaccination rates. The goal of this research was to evaluate rural community member knowledge of influenza and influenza vaccine. Methods: A cross-sectional survey was conducted with residents of a rural a medically underserved community in Washington State. Three thousand rural residents were contacted up to five times by a survey research center with a request to participate, with the goal of receiving 500 returned surveys based on the current population size, a z-score of 95, and an error rate of 5%. The survey evaluated rural resident knowledge and opinions about influenza and influenza vaccine. Results: Participants who were vaccinated against influenza in the last five years were more likely to know that influenza vaccine does not cause influenza (χ² = 13.44, p < 0.01) and that antibiotics cannot be used to treat influenza (χ² = 19.36, p < 0.01) than people who were not vaccinated. There was no statistical difference between people who are vaccinated and unvaccinated regarding knowing that influenza is viral rather than bacterial with the majority in both groups responding correctly (χ² = 0.05, p < 0.82), or that people who have influenza are at higher risk for contracting pneumonia (χ² = 0.78, p = 0.08) or COVID-19 (χ² = 1.54, p = 0.21). Unvaccinated people were more likely to have had their opinion about vaccines changed in recent years (p < 0.01) and feel that COVID-19 impacted their ability to trust public health officials (p < 0.01). Conclusions: Understanding gaps that exist in rural resident knowledge about influenza could be valuable in developing future educational outreach efforts in these communities.

Personalized cancer vaccines represent a revolutionary frontier in oncology, harnessing the unique genetic and molecular profile of individual tumors to elicit targeted immune responses. This review provides a comprehensive overview of the current landscape and future perspectives of neoantigen-based personalized cancer vaccines, encompassing peptide, mRNA, DNA, autologous dendritic cell, and viral or bacterial vector platforms. We further discuss the integration of immune adjuvants, delivery systems, and combinational strategies, particularly with immune checkpoint inhibitions, to overcome tumor-induced immune exhaustion and improve therapeutic efficacy. Despite significant clinical progress over the past decade in this space, major challenges remain in immunogenic neoantigens prediction, streamlining individualized vaccine manufacturing, and optimization of combinational regimens to maximize durable antitumor responses. By reviewing recent preclinical and clinical studies on neoantigen-based cancer vaccines, this review highlights key advances, identifies persistent translational bottlenecks, and underscores the need for biomarker-guided mechanistically informed trials to fully unleash the clinical potential of neoantigen-based personalized cancer vaccines in the era of precision immuno-oncology.

Background/objectives: Toxoplasmosis caused by Toxoplasma gondii still poses a serious threat to public health in most countries and regions. Currently, the lack of effective vaccines necessitates the urgent development of a safe and effective vaccine.

Methods: In this study, we combined the inactivated T. gondii vaccine with a colloidal manganese salt (Mn jelly [MnJ]) adjuvant.

Results: This triggered a powerful innate immunity, significantly increased the number of CD4⁺ and CD8⁺ T cells secreting interferon γ (IFN-γ) in mice, and enhanced the generation of CD8⁺ central memory T cells and CD8⁺ effector memory T cells. Compared to the control groups, mice in experimental groups produced more specific IgG, and produced high levels of IL-2, IL-12 and IFN-γ. The survival rate of mice in experimental groups reached 50%, while all control group mice died within 9 days during T. gondii acute infection. Furthermore, the burden of brain cysts in experimental group mice was also significantly reduced by 90.77% compared to the control group during chronic infection.

Conclusions: These results suggested that the incorporation of an MnJ adjuvant significantly enhances the immunoprotective efficacy of inactivated T. gondii vaccine, positioning this formulation as a promising candidate for development against toxoplasmosis.

Background: Patients with autoimmune rheumatic diseases (ARDs) such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are at increased risk of infections due to immune dysregulation and immunosuppressive therapy. Vaccination is a cornerstone of infection prevention, but uptake is still inadequate.

Methods: We conducted an observational, multicenter study at four Italian rheumatology centers. Adult patients with RA or SLE on immunosuppressive therapy completed a standardized questionnaire assessing demographics, disease activity, treatments, vaccination status for influenza, pneumococcus, varicella-zoster virus [VZV], hepatitis B virus [HBV], human papillomavirus [HPV], adverse events, and reasons for or against vaccination.

Results: A total of 325 patients were included (226 RA, 99 SLE; median age 60 years; 84.6% females). Overall vaccine coverage was 68.0%, with influenza being the most frequent (54.2%), followed by pneumococcal (30.8%), HBV (21.2%), VZV (12.9%) and HPV (5.9%). RA patients showed higher influenza and pneumococcal uptake, while HBV vaccine was more common in SLE. Education was associated with higher pneumococcal and HBV coverage in both groups. Major adverse events and disease flares were rare. Physician recommendation was the main motivator, with rheumatologists driving VZV uptake and general practitioners influencing influenza and HBV. Among unvaccinated patients, the leading barrier was not being offered vaccination (42.5%), followed by concerns about efficacy/safety (18.3%) and lack of awareness (15.7%). Cluster analysis identified three subgroups: "Not offered" (largest), "Unaware," and "Skeptical," with age distribution differing across clusters.

Conclusions: Vaccination coverage among Italian ARD patients remains insufficient. Physician recommendation is pivotal, while lack of physician offer and awareness are major barriers. Targeted educational strategies and proactive physician involvement are needed to improve vaccine uptake in this high-risk population.

Background: Norovirus is a leading cause of epidemic acute gastroenteritis worldwide, associated with significant morbidity, mortality, and economic loss. Despite its global impact, no licensed vaccine is currently available, and vaccine development remains challenging.

Methods: We explored avian immunoglobulin Y (IgY) antibodies as a low-cost countermeasure against norovirus infection. We generated recombinant protruding (P) domain proteins from the capsid protein (VP1) of noroviruses, representing two GII.4 variants and the GII.6 genotype. These were combined into a single immunogen to immunize laying hens to produce norovirus VP1-specific IgY antibodies.

Results: Immunization of laying hens with the P domain proteins elicited high-titer (>1:450,000) P domain-specific IgY antibodies. The yolk-derived IgY effectively inhibited binding of various norovirus P particles to their histo-blood group antigen ligands, with 50% blocking titers (BT50) up to 1:8533 against homotypic GII.4 and 1:667 against heterotypic G1.1 Norwalk virus P particles. Importantly, the IgY neutralized replication of GII.4 norovirus in the human intestinal enteroid (HIE) system at a high titer of over 1:2500, equivalent to 0.70 µg/mL of total IgY. We also produced norovirus shell (S) domain proteins and corresponding IgY antibodies, which neutralized GII.4 norovirus replication in the HIE model at a titer of ~1:800, equivalent to 2.98 µg/mL of total IgY. This provides the first evidence that the S domain contains neutralizing epitopes.

Conclusions: Our findings support the potential of IgY targeting norovirus P or S domains as a scalable, cost-effective strategy for preventing norovirus infection and disease.