Human Vaccines & Immunotherapeutics最新文献

The mechanisms of Pythium insidiosum-antigen (PIA) immunotherapy activating a patient's immune system are unknown. We evaluated the interleukin-8 (IL-8) serum levels during P. insidiosum infection and after vaccination with PIA in vascular pythiosis cases. Furthermore, we studied the anti-P. insidiosum activity of neutrophils stimulated with various concentrations of PIA ex vivo in 3 strains of P. insidiosum isolated from vascular pythiosis patients. IL-8 serum levels were evaluated using the ELISA technique. We assessed the effect of PIA-stimulated neutrophils on the viability of zoospores using MTT assay, visualized neutrophil extracellular trap (NET) formation via microscopy, and measured the levels of double-stranded DNA (dsDNA) using PicoGreen dsDNA quantitation assay in 3 strains of P. insidiosum isolated from vascular pythiosis patients. Serum levels of IL-8 gradually lowered from the early to the end phases of vaccination with PIA among the surviving group of vascular pythiosis cases. Neutrophils stimulated with 0.01 µg/ml PIA reduced zoospore viability significantly compared to PIA-unstimulated neutrophils for strain 1 and strain 3 (p < .05). Neutrophils stimulated with 0.01, 0.1, 1, and 10 µg/ml PIA exhibited significantly lower zoospore viability than PIA-unstimulated neutrophils for strain 2 (p < .05). IL-8 can be used as a biomarker for monitoring vascular pythiosis cases treated with the PIA vaccine. Also, anti-P. insidiosum activity of PIA-stimulated neutrophils was probably due to the disruption of cellular activity in zoospores rather than the mechanisms based on the formation of NETs.

Current influenza vaccines could be augmented by including recombinant neuraminidase (rNA) protein antigen to broaden protective immunity and improve efficacy. Toward this goal, we investigated formulation conditions to optimize rNA physicochemical stability. When rNA in sodium phosphate saline buffer (NaPBS) was frozen and thawed (F/T), the tetrameric structure transitioned from a "closed" to an "open" conformation, negatively impacting functional activity. Hydrogen deuterium exchange experiments identified differences in anchorage binding sites at the base of the open tetramer, offering a structural mechanistic explanation for the change in conformation and decreased functional activity. Change to the open configuration was triggered by the combined stresses of acidic pH and F/T. The desired closed conformation was preserved in a potassium phosphate buffer (KP), minimizing pH drop upon freezing and including 10% sucrose to control F/T stress. Stability was further evaluated in thermal stress studies where changes in conformation were readily detected by ELISA and size exclusion chromatography (SEC). Both tests were suitable indicators of stability and antigenicity and considered potential critical quality attributes (pCQAs). To understand longer-term stability, the pCQA profiles from thermally stressed rNA at 6 months were modeled to predict stability of at least 24-months at 5°C storage. In summary, a desired rNA closed tetramer was maintained by formulation selection and monitoring of pCQAs to produce a stable rNA vaccine candidate. The study highlights the importance of understanding and controlling vaccine protein structural and functional integrity.

This is a response to Marchand & Masoud's response letter regarding my criticism "Response to Dr. Somovilla del Saz's letter to the editor regarding "Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies."" The response is a defense of the initial criticism to the paper regarding the validity of the inclusion of Ladapo´s paper.

Enhanced Passive Safety Surveillance (EPSS) was conducted for quadrivalent inactivated split-virion influenza vaccines (IIV4) in Germany (high dose [HD]) and Finland (standard dose [SD]) for the northern hemisphere (NH) 2022/23 influenza season. The primary objective was to assess adverse events following immunization (AEFI) occurring ≤7 days post-vaccination. In each country, the EPSS was conducted at the beginning of the NH influenza season. Exposure information was documented using vaccination cards (VC), and AEFI were reported via an electronic data collection system or telephone. AEFI were assessed by seriousness and age group (Finland only). The vaccinee reporting rate (RR) was calculated as the number of vaccinees reporting ≥ 1 AEFI divided by the total vaccinees. In Germany, among 1041 vaccinees, there were 31 AEFI (ten vaccinees) during follow-up, including one serious AEFI. Of 16 AEFI (six vaccinees) with reported time of onset, 15 occurred ≤7 days post-vaccination (RR 0.58%, 95% confidence interval [CI] 0.21, 1.25), which was lower than the 2021/22 season (RR 1.88%, 95% CI: 1.10, 3.00). In Finland, among 1001 vaccinees, there were 142 AEFI (51 vaccinees) during follow-up, none of which were serious. Of 133 AEFI (48 vaccinees) with time of onset reported, all occurred ≤7 days post-vaccination (RR 4.80%, 95% CI: 3.56, 6.31), which was similar to the 2021/22 season (RR 4.90%, 95% CI: 3.65, 6.43). The EPSS for HD-IIV4 and for SD-IIV4 in the 2022/23 influenza season did not suggest any clinically relevant changes in safety beyond what is known/expected for IIV4s.

There is an ongoing burden of pneumococcal disease in children despite the use of pneumococcal conjugate vaccines (PCVs). This phase 3, open-label, single-arm, multisite, descriptive study was designed to evaluate the safety and immunogenicity of a 3 + 1 regimen of V114 (VAXNEUVANCE™), a 15-valent PCV, in South Korean infants and toddlers. Adverse events (AEs) were reported for 14 d following any vaccination, and throughout the study period for serious AEs. Serotype-specific immunoglobulin G (IgG) response rates (proportion of participants meeting an IgG threshold value of ≥0.35 μg/mL) and geometric mean concentrations (GMCs) for the 15 serotypes at 30 d postdose 3 (PD3) and at 30 d postdose 4 (PD4) were evaluated as endpoints. Healthy infants enrolled at 42-90 d after birth were vaccinated with V114 (N = 57). The most commonly reported AEs were those solicited in the trial. The majority of reported AEs were transient and of mild or moderate intensity. Few serious AEs were reported; none were vaccine related. No participants died nor discontinued the study vaccine because of an AE. V114 was immunogenic for all 15 serotypes contained in the vaccine, as assessed by IgG response rates at 30 d PD3 and IgG GMCs at 30 d PD3 and at 30 d PD4. V114 was well tolerated and immunogenic when administered as a 3 + 1 regimen in healthy South Korean infants and toddlers.

Cell-based therapeutic cancer vaccines use autologous patient-derived tumor cells, allogeneic cancer cell lines or autologous antigen presenting cells to mimic the natural immune process and stimulate an adaptive immune response against tumor antigens. The primary objective of this study is to perform a systematic literature review with an embedded meta-analysis of all published Phase 2 and 3 clinical trials of cell-based cancer vaccines in human subjects. The secondary objective of this study is to review trials demonstrating biological activity of cell-based cancer vaccines that could uncover additional hypotheses, which could be used in the design of future studies. We performed the systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The final review included 36 studies - 16 single-arm studies, and 20 controlled trials. Our systematic review of the existing literature revealed largely negative trials and our meta-analysis did not show evidence of clinical benefit from cell-based cancer-vaccines. However, as we looked beyond the stringent inclusion criteria of our systematic review, we identified significant examples of biological activity of cell-based cancer vaccines that are worth highlighting. In conclusion, the existing literature on cell-based cancer vaccines is highly variable in terms of cancer type, vaccine therapies and the clinical setting with no overall statistically significant clinical benefit, but there are individual successes that represent the promise of this approach. As cell-based vaccine technology continues to evolve, future studies can perhaps fulfill the potential that this exciting field of anti-cancer therapy holds.

In 2020, there were approximately 50,865 anal cancer cases and 36,068 penile cancer cases worldwide. HPV is considered the main causal agent for the development of anal cancer and one of the causal agents responsible for the development of penile cancer. The aim of this epidemiological, descriptive, retrospective study was to describe the burden of hospitalization associated with anal neoplasms in men and women and with penis neoplasms in men in Spain from 2016 to 2020. The National Hospital Data Surveillance System of the Ministry of Health, Conjunto Mínimo Básico de Datos, provided the discharge information used in this observational retrospective analysis. A total of 3,542 hospitalizations due to anal cancer and 4,270 hospitalizations due to penile cancer were found; For anal cancer, 57.4% of the hospitalizations occurred in men, and these hospitalizations were also associated with significantly younger mean age, longer hospital stays and greater costs than those in women. HIV was diagnosed in 11.19% of the patients with anal cancer and 1.74% of the patients with penile cancer. The hospitalization rate was 2.07 for men and 1.45 for women per 100,000 in anal cancer and of 4.38 per 100,000 men in penile cancer. The mortality rate was 0.21 for men and 0.12 for women per 100,000 in anal cancer and 0.31 per 100.000 men in penile cancer and the case-fatality rate was 10.07% in men and 8,26% in women for anal cancer and 7.04% in penile cancer. HIV diagnosis significantly increased the cost of hospitalization. For all the studied diagnoses, the median length of hospital stays and hospitalization cost increased with age. Our study offers relevant data on the burden of hospitalization for anal and penile cancer in Spain. This information can be useful for future assessment on the impact of preventive measures, such as screening or vaccination in Spain.

Despite the ongoing global vaccination campaign aimed at preventing human papillomavirus (HPV) related health issues, the uptake of the HPV vaccine remains unacceptably low in developing regions, particularly in sub-Saharan Africa (SSA). Therefore, this systematic review and meta-analysis aimed at determining the pooled prevalence and associated factors of HPV vaccine uptake among adolescent school girls in SSA. Electronic bio-medical databases were explored. Pooled prevalence, publication bias, meta-regression, sub-group, and sensitivity analysis were performed. The estimated pooled prevalence of HPV vaccine uptake was 28.53% [95% CI: (5.25, 51.81)]. Having good knowledge and a positive attitude was significantly associated with HPV vaccine uptake in SSA. Subgroup analysis revealed the highest uptake was 62.52% from Kenya and the lowest was 3.77% in Nigeria. The HPV vaccine uptake is low. It underscores the need for community education, school-based immunization, and education programs that promote the uptake of the vaccine to increase coverage.

Coronavirus disease 2019 (COVID-19) was extraordinarily harmful, with high rates of infection and hospitalization. This study aimed to evaluate the impact of COVID-19 vaccination status and other factors on hospitalization and disease severity, using data from Nagasaki Prefecture, Japan. Confirmed cases of COVID-19 infection with vaccination status were included and the differences in characteristics between different vaccination statuses, hospitalization or not, and patients with varying levels of disease severity were analyzed. Furthermore, logistic regression was used to calculate odds ratio (ORs) and 95% confidence intervals (CI) to evaluate the association of various factors with hospitalization and disease severity. From March 14, 2020 to August 31, 2022, 23,139 patients were unvaccinated 13,668 vaccinated the primary program with one or two doses, and 4,575 completed the booster. Vaccination reduced the risk of hospitalization with an odd ratio of 0.759 (95% CI: 0.654-0.881) and the protective effect of completed booster vaccination was more pronounced (OR: 0.261, 95% CI: 0.207-0.328). Similarly, vaccination significantly reduced the risk of disease severity (vaccinated primary program: OR: 0.191, 95% CI: 0.160-0.228; completed booster vaccination: OR: 0.129, 95% CI: 0.099-0.169). Overall, unvaccinated, male, elderly, immunocompromised, obese, and patients with other severe illness factors were all risk factors for COVID-19-related hospitalization and disease severity. Vaccination was associated with a decreased risk of hospitalization and disease severity, and highlighted the benefits of completing booster.