Therapeutic Advances in Vaccines and Immunotherapy最新文献

Background: Health care workers are considered as high-risk population, who deal with many unknown, undiagnosed, and subclinical infectious diseases in their daily life. Currently, the COVID-19 pandemic posed as an add-on burden for these frontline workers in all aspects. Although, many adverse physical and mental effects of pandemic among health care workers (HCWs) were discussed worldwide, a long-term study for delayed complications needed to be explored.

Aim: The study evaluates and compares three waves of the pandemic in various aspects such as the incidence, prevalence, severity, risk factors, and variations in the pattern of COVID-19 infection, impact of vaccination, and post-infection complications among the HCWs.

Methodology: A longitudinal observational study was carried out over a period of 2 years and another 6 months for follow-up. The study included all HCWs who tested positive in any one wave of COVID-19 pandemic with any one of the confirmed COVID-19 test. Each COVID-19-affected HCW was followed up through telephone calls and direct interviews conducted at the study site. Admission details and other background details of the study population were collected from the hospital records.

Results: A total of 968 HCWs were COVID-19 positive in any of the three waves, and highest incidence (53.00%) was caused by the Omicron variant. High severity and hospitalization was observed in the first wave (no vaccination) and fully immunized personnel were found to be out of danger of being hospitalized during all succeeding waves (chi-square value: 87.04, p < 0.05). Predictors such as female gender, occupational exposure, and comorbid status were identified as possible risk factors for infection. A total of 70 HCWs reported with 104 complications, of which chronic diseases such as new onset of diabetes (n = 3), cardiovascular events (n = 8), worsening of preexisting comorbidities (n = 8), etc. were found out.

Conclusions: This study proves the benefit of being immunized rather than the risk of being infected. This study documents that immunization impacted complication and hospitalization rates of COVID-19 infection. This evidence may help in tackling vaccine hesitancy across the nations.

Dendritic cells (DC) are postulated to play a role in autoimmune diseases such as Systemic Lupus Erythematosus (SLE). We reported a 13-year-old female SLE patient who presents with chronic arthritis accompanied by persistent fever, dyspnea, sleep disturbance, headache, stomatitis, rash, and muscle weakness. The supporting examinations showed abnormal blood cell counts, positive antinuclear antibody profile, serositis, and neuropathy. Immunosuppressants failed to improve the condition. DC-based vaccine derived from autologous peripheral blood which was introduced with SARS-CoV-2 protein was given to this patient. There was a significant improvement in clinical and laboratory findings. Thus, DC immunotherapy appears to be a potential novel therapy for SLE that needs to be studied.

Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease associated with significant morbidity and mortality. Rituximab is a B-cell depleting therapy utilized in the treatment of SLE. In adults, rituximab has been associated with increased risk of adverse outcomes in patients who develop coronavirus disease 2019 (COVID-19). We aimed to assess the impact of prior rituximab treatment on clinical outcomes from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in children with SLE. To describe the impact of rituximab on outcomes from SARS-CoV-2 infection, we conducted a retrospective study of pediatric SLE patients in our center diagnosed with COVID-19 who had previously received rituximab between February 2019 and October 2022. Patients' clinical characteristics, disease activity, and outcomes were assessed. Of the eight subjects assessed, five required hospitalizations for COVID-19, four required ICU admission, and two were seen in the emergency department for their symptoms. One patient ultimately expired from her illness. The median time between rituximab administration and COVID-19 diagnosis was 3 months. We assessed the clinical outcomes, including the need of ICU admission and fatal outcome, of COVID-19 in our cSLE patient population after rituximab administration. Approximately 60% of our patients required hospitalization for their illness, and seven out of eight patients required healthcare utilization to include hospitalization and/or emergency department visits.

Children with paediatric rheumatic diseases (PRDs) are at increased risk of vaccine-preventable disease. Safe and effective vaccination is central to preventive care in PRD patients; however, uncertainty surrounding immunogenicity and safety has contributed to suboptimal vaccination. The aim of this study was to evaluate treatment effect on immunogenicity to vaccination in PRD patients and assess vaccine safety, specifically adverse events following immunisation (AEFI) and disease flare. Scoping review. In this scoping review, a systematic search of PubMed, CINAHL and Embase databases was conducted from 2014 to 23 August 2022 to identify observational studies evaluating the immunogenicity and safety of commonly used vaccinations in PRD patients. The primary outcome was immunogenicity (defined as seroprotection and protective antibody concentrations), with secondary outcomes describing AEFI and disease flare also extracted. Due to extensive heterogeneity related to diagnostic and vaccination variability, narrative synthesis was used to describe the findings of each study. Study quality was assessed via the Mixed Methods Appraisal Tool. The review was prospectively registered with PROSPERO (CRD42022307212). The search yielded 19 studies evaluating immunogenicity to vaccination and incidence of AEFI and disease flares in this population, which were of acceptable quality. Corticosteroids did not have deleterious effects on vaccine response. Treatment with conventional disease-modifying antirheumatic drugs (DMARDs) and biologic DMARDs generally had no effect immunogenicity in PRD patients. While patients exhibited adequate seroprotection, protective antibody levels were lower in patients on some immunosuppressant agents. Varicella infections were recorded post vaccination in several patients with low protective antibody levels undergoing treatment with DMARDs and corticosteroids. Most vaccines appear safe and effective in PRD patients, despite immunosuppressant treatment. Booster vaccinations should be considered with some studies highlighting inadequate seroprotection following primary course of vaccinations with acceleration of antibody decline over time. There was limited evidence to support avoiding live vaccines in PRD patients.

Checkpoint markers and immune checkpoint inhibitors have been increasingly identified and developed as potential immunotherapeutic targets in various human cancers. Despite valuable efforts to discover novel immune checkpoints and their ligands, the precise roles of their therapeutic functions, as well as the broad identification of their counterpart receptors, remain to be addressed. In this context, it has been suggested that various putative checkpoint receptors can be induced upon activation. In the tumor microenvironment, T cells, as crucial immune response against malignant diseases as well as other immune central effector cells, such as natural killer cells, are regulated via co-stimulatory or co-inhibitory signals from immune or tumor cells. Studies have shown that exposure of T cells to tumor antigens upregulates the expression of inhibitory checkpoint receptors, leading to T-cell dysfunction or exhaustion. Although targeting immune checkpoint regulators has shown relative clinical efficacy in some tumor types, most trials in the field of cancer immunotherapies have revealed unsatisfactory results due to de novo or adaptive resistance in cancer patients. To overcome these obstacles, combinational therapies with newly discovered inhibitory molecules or combined blockage of several checkpoints provide a rationale for further research. Moreover, precise identification of their receptors counterparts at crucial checkpoints is likely to promise effective therapies. In this review, we examine the prospects for the application of newly emerging checkpoints, such as T-cell immunoglobulin and mucin domain 3, lymphocyte activation gene-3, T-cell immunoreceptor with Ig and ITIM domains (TIGIT), V-domain Ig suppressor of T-cell activation (VISTA), new B7 family proteins, and B- and T-cell lymphocyte attenuator, in association with immunotherapy of malignancies. In addition, their clinical and biological significance is discussed, including their expression in various human cancers, along with their roles in T-cell-mediated immune responses.

Background: Vaccination is a safe and effective way to prevent disease and save lives, but it may also produce some undesirable adverse events (AEs)which may affect healthy individuals. Therefore, the monitoring of AE following immunization (AEFIs) is necessary. The objective of this study was to assess the AEs following COVID-19 vaccinations in a tertiary care hospital.

Methodology: The study was conducted as active vaccine safety surveillance for a period of 6 months among the COVID-19 vaccine beneficiaries of the study site. Active surveillance was conducted via initiating two telephone contacts. The first surveillance was conducted in 8 days and the second surveillance after 28 days of post-vaccination. All identified AEs following immunizations (AEFIs) were reported and analysed by the AEFI investigation team at the study site. The causality assessment of each identified AEFI was performed using the World Health Organization's causality assessment algorithm.

Results: A total of 2927 enrolled study population completed the study with a response rate of 80.85%. The study identified 902 AEFIs from 614 study populations with an incidence rate of 20.97%. Of which 794 and 79 AEFIs were associated with COVISHIELD™ and COVAXIN^®, respectively. The majority of the events were reported among the age group of 18-29 years. Overall, only three events were serious and no deaths were reported among the study population. A total of 75.59% of events had a consistent causal association with vaccination and were categorized as vaccine product-related reactions. The study identified various factors such as gender (p = 0.019), age (p < 0.05), co-morbid status (p = 0.032) and dose number (p = 0.001) as potential predictors for development of AEFI.

Conclusion: The study identified only 0.33% of events as serious, and 99.67% of the study population recovered from the AEFIs, which reveals that COVISHIELD™ and COVAXIN^® have a generally favourable safety profile. However, close monitoring is required to identify the potential signals, as the safety data from the clinical trials are limited.

Background: Patients with plasma cell dyscrasia are at a higher risk of developing a severe Coronavirus-2019 (COVID-19) infection. Here we present a systematic review of clinical studies focusing on the immune response to the COVID-19 vaccination in patients with plasma cell dyscrasia.

Objectives: This study aims to evaluate the immune response to COVID-19 vaccines in patients with plasma cell dyscrasia and to utilize the results to improve day-to-day practice.

Design: Systematic Review.

Methods: Online databases (PubMed, CINAHL, Ovid, and Cochrane) were searched following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Only articles published in the English language were included. Out of 59 studies, nine articles (seven prospective and two retrospective studies) were included in this systematic review. Abstracts, case reports, and case series were excluded.

Results: In all nine studies (N = 1429), seroconversion post-vaccination was the primary endpoint. Patients with plasma cell disorders had a lower seroconversion rate compared to healthy vaccinated individuals and the overall percentage of seroconversion ranged between 23% and 95.5%. Among patients on active therapy, lower seroconversion rates were seen on an anti-CD38 agent, ranging from 6.5 up to 100%. In addition, a significantly lower percentage was recorded in older patients, especially in those aged equal to or greater than 65 years and those who have been treated with multiple therapies previously. Only one study reported a statistically significant better humoral response rate with the mRNA vaccine compared to ADZ1222/Ad26.Cov.S.

Conclusion: Variable seropositive rates are seen in patients with plasma cell dyscrasia. Lower rates are reported in patients on active therapy, anti-CD38 therapy, and elderly patients. Hence, we propose patients with plasma cell dyscrasias should receive periodic boosters to maintain clinically significant levels of antibodies against COVID-19.

Registration: PROSPERO ID: CRD42023404989.

Background: Vaccines against COVID-19 are critical for preventing and managing COVID-19 because immunization is one of the most active and cost-effective health strategies for infectious disease prevention. Knowing the community's willingness and factors affecting COVID-19 vaccine acceptance will support the design of effective promotion strategies. Therefore, this study was aimed at assessing COVID-19 vaccine acceptance and its determinants among the Ambo Town community.

Method: A community-based, cross-sectional study was conducted using structured questionnaires from 1 to 28 February 2022. Four kebeles were selected randomly, and the systematic random sampling procedure was used to select the households. SPSS-25 software was used for data analysis. Ethical approval was received from the Institutional Review Committee of the College of Medicine and Health Sciences of Ambo University, and data were kept confidential.

Result: Of the 391 participants, 385 (98.5%) of the respondents were not vaccinated for COVID-19, and around 126 (32.2%) of the respondents said that they would receive the vaccine if the government provided it. The multivariate logistic regression analysis revealed that males were 1.8 times more likely to accept the COVID-19 vaccine (adjusted odds ratio (AOR) = 1.8, 95% CI: 1.074-3.156) as compared to females. The acceptance of the COVID-19 vaccine was lower by 60% in those who tested for COVID-19 as compared to those who were not tested (AOR = 0.4, 95% CI: 0.27-0.69). Moreover, the participants who had chronic diseases were two times more likely to accept the vaccine. Acceptance of the vaccine was reduced by half among those who believed that there was a scarcity of data on its safety (AOR = 0.5, 95% CI: 0.26-0.80).

Conclusion: The prevalence of COVID-19 vaccination acceptance was low. To enhance the acceptance of the COVID-19 vaccine, the government and different stakeholders should strengthen public education using mass media about the advantages of getting the COVID-19 vaccination.

Background and aims: Influenza is an acute respiratory disease with the highest mortality rate in the high-risk groups. Vaccination is a key public health strategy to prevent influenza in high-risk people. This study aimed to assess the influenza vaccination coverage rate and identify its demographic determinants in patients with end-stage renal disease (ESRD), chronic obstructive pulmonary disease (COPD), and diabetes in Birjand, Eastern Iran.

Methods: This cross-sectional study included 400 patients (300 diabetic, 60 dialysis, and 40 COPD patients) from September 2017 to August 2018. Using interview method, we completed a questionnaire containing the patients' demographic characteristics, questions about patients' knowledge and attitude toward influenza vaccination, the influenza vaccination history, and the most common causes for vaccination. The relationship between the type of disease and patients' characteristics (exposure) with vaccination coverage (outcome) was investigated.

Results: The mean age of participants was 58.7 ± 11.3 years. Also, 58.8% of the patients received at least one dose of the vaccine and the regular injection rate was 32.8%. The coverage of influenza vaccine in dialysis patients was significantly higher than other patients (p < 0.001). The mean knowledge score was 6.17 ± 2.15 out of maximum 9 scores. There was a positive association between age [p = 0.001, odds ratio (OR) = 1.04] and patients' knowledge (p < 0.001, OR = 1.42) with the vaccination coverage.

Conclusion: The coverage of influenza vaccine in high-risk patients in Birjand was low. Hence, it is essential to increase the knowledge of high-risk groups about the importance of influenza vaccination and facilitate their access to vaccines.

Background and aims: The peak of the third wave of COVID-19 infection was in the summer (August-September) of 2021, dominated by the Delta variant. Florida was the epicenter of the third wave with more than 151,449 cases in the first week of August with a positivity rate of 20%. The purpose of this study is to identify the percentage of COVID-19 infection in vaccinated patients in a minority population in south Florida and to elucidate the relationship, if any, between demographics and breakthrough infections, the rate of vaccine hesitancy, as well as the willingness to receive the monoclonal antibody REGEN-COV for the treatment of COVID-19.

Methods: This cross-sectional study was performed at the Emergency Department, Larkin Community Hospital Palm Spring Campus, located in Hialeah, the fourth largest city in Florida. Hialeah is dominated (94.7%) by Hispanics and Latinos. This city represents a cross-sectional sample of US cities in general and Florida in specific. We enrolled 127 COVID-19 PCR-positive patients.

Results: The infection in vaccinated patients (breakthrough) was found to be about one in three (34%). Despite the high infection rate and mounting death toll, about 73% of our unvaccinated patients answered no to the question 'knowing the consequences of being infected with COVID-19 and the fact that you are positive, would you have chosen to be vaccinated earlier?' However, about 27% of these patients agreed to receive the vaccine and 20.5% received the monoclonal antibody REGEN-COV.

Conclusions: Our study revealed that vaccine hesitancy in South Florida continues to be a major challenge, especially with the emergence of mutations including Delta plus and Omicron.