Vaccines最新文献

Background: Combining radiotherapy with targeted therapy benefits patients with advanced epidermal growth factor receptor-mutated non-small cell lung cancer (EGFRm NSCLC). However, the optimal strategy to combine EGFR tyrosine kinase inhibitors (TKIs) with radiotherapy for maximum efficacy and minimal toxicity is still uncertain. Notably, EVs, which serve as communication mediators among tumor cells, play a crucial role in the anti-tumor immune response. Methods To exploit the role of EVs in the delivery of tumor antigens, we formulated a therapeutic strategy that involves the use of radiation-induced tumor-derived EVs (TEXs) loaded onto dendritic cells (DCs) as a kind of vaccine in conjunction with EGFR TKIs and assessed the efficacy and safety of this approach in the treatment of EGFRm NSCLC. Results In our study, we characterized the release of immunogens as influenced by various modes of cell death, examining the impact of different levels of cell death under diverse irradiation modalities. Our results demonstrated that a radiation mode of 6Gy*3f exhibited the most promising potential to stimulate anti-tumor immune responses. This radiotherapy fraction, combined with TKIs, showed promising results in a tumor-bearing mouse model with an EGFR mutation, although there is a risk of radiation-associated pneumonitis. Furthermore, we found that 6Gy*3f-TEXs in vitro activate DCs and promote T cell proliferation as well as cytotoxic T lymphocyte-mediated tumor cell destruction. The administration of EGFR-TKIs combined DCs loaded with 6Gy*3f-TEXs exhibited the potential to inhibit tumor growth and mitigate the risk of pneumonitis. Together, the research shows that TEXs from high-dose fractionation radiation can mature DCs and boost the killing of cytotoxic T lymphocytes. Combining these DC vaccines with Osimertinib offers a promising and safe treatment for EGFRm NSCLC.

Background/objectives: Since 2022, outbreaks of monkeypox have raised widespread concern and have been declared a public health emergency of international concern by the World Health Organization. There is an urgent need to develop a safe and effective vaccine against the monkeypox virus (MPXV). Recombinant protein vaccines play a significant role in the prevention of infectious diseases due to their high safety and efficacy.

Methods: We used the A29, E8, M1, A35, and B6 proteins of MPXV as candidate antigens to generate a panel of multi-component MPXV vaccine candidates, which were administered subcutaneously to immunize mice.

Results: The results showed that the vaccine candidates Mix-AEM, Mix-AEMA, Mix-AEMB, and Mix-AEMAB effectively elicited strong neutralizing antibody responses and demonstrated significant protection against vaccinia virus (VACV) infection in a murine model. The vaccine candidate Mix-AEM induced significantly higher levels of neutralizing antibodies, cellular immunity capacity, and virus clearance compared to the vaccine candidate Mix-AE (lacking M1). Single-component immunization showed that M1 induced higher levels of neutralizing antibodies than A29 and E8. These results indicated that M1 is a critical and essential antigen in the MPXV vaccine. The number of cells secreting IFN-γ was significantly increased in the Mix-AEMA and Mix-AEMAB groups compared to the A35-deficient vaccine candidates, demonstrating the important role of A35 in inducing IFN-γ secreting. In addition, the neutralizing antibodies induced by these multi-component vaccine candidates were maintained at high levels six months after the third immunization.

Conclusions: In summary, this study lays the groundwork for combining antigens to develop multi-component subunit vaccines.

Background/Objectives: Healthcare professionals (HCPs) hold significant influence over public attitudes toward vaccinations. Studies suggest that HCPs are hesitant towards the coronavirus disease 2019 (COVID-19) vaccines. This hesitancy could lead to lower vaccination rates in the community. Therefore, this scoping review aimed to assess the extent of hesitancy towards COVID-19 booster doses among HCPs and identify the associated factors. Methods: A comprehensive search was conducted in the PubMed and Scopus databases from April to August 2024, using keywords related to COVID-19, vaccine hesitancy, HCPs, and booster vaccination. Studies that had been peer-reviewed, published in English after 2022, and focused on the hesitancy of the COVID-19 booster dose hesitancy among HCPs were included. Out of the 6703 studies screened, 24 studies were included. Results: Most of the HCPs have received their initial series of COVID-19 vaccinations. However, there is a lower rate of uptake for booster doses, with hesitancy rates ranging from 12% to 66.5%. Hesitancy rates varied significantly across continents, with Asia, Africa, and Europe ranging from 19.7% to 66.5%, 27% to 46.1%, 14% to 60.2%, respectively. Hesitancy was reported to be influenced by various factors, including concerns about vaccine safety, necessity, and effectiveness of these vaccines. In addition, the hesitancy regarding booster doses was also found to be influenced by factors like age, gender, profession, and previous COVID-19. Physicians, nurses, and pharmacists exhibited vaccine hesitancy rates ranging from 12.8% to 43.7%, 26% to 37%, and 26% to 34.6%, respectively. Conclusions: Our review underscores the hesitancy among HCPs towards receiving booster doses across countries around the world and explores the underlying factors. These findings provide valuable insights for the design of future pandemic vaccination programs.

Background/Objectives: African swine fever virus (ASFV) is a devastating disease affecting domestic and wild suids and causing significant economic losses in the global pig industry. Attenuated modified live virus (MLV) vaccines are the most promising approaches for vaccine development. This study aimed to evaluate the safety and efficacy of four recombinant ASFV genotype II strains, derived from the non-hemadsorbing (non-HAD) attenuated isolate Lv17/WB/Rie1, through the single or simultaneous deletion of virulence-associated genes. Methods: Recombinant viruses were engineered by deleting the UK, EP402R, and EP153R genes, either individually or in combination. Four recombinant strains were evaluated for safety and efficacy in domestic pigs vaccinated intramuscularly with 10² TCID₅₀. Clinical signs, viremia, virus shedding, and antibody responses were monitored. Protection efficacy was assessed by challenging vaccinated pigs with the virulent genotype II Armenia07 strain. Additionally, a reversion-to-virulence study involving an overdose of the vaccine candidate was conducted to evaluate its stability through serial immunizations. Results: Deletion of the UK gene alone increased virulence, whereas the double deletion of EP402R and EP153R (Lv17/WB/Rie1-ΔCD) significantly enhanced safety while maintaining full protective efficacy. Vaccinated pigs exhibited reduced viremia, no virus shedding, and robust virus-specific antibody responses, achieving complete protection against Armenia07. The reversion-to-virulence study revealed potential but limited pathogenicity after multiple passages, indicating areas for improvement in vaccine stability. Conclusions: The Lv17/WB/Rie1-ΔCD strain demonstrates excellent safety and efficacy, along with potential DIVA (differentiating infected from vaccinated animals) compatibility, positioning it as a strong candidate for an ASFV MLV vaccine. Further research is needed to refine the vaccine and address the potential risks of reversion to virulence.

Background/objectives: Coronavirus-19 (COVID-19) vaccines represent a significant milestone in the fight against coronavirus disease. Ongoing post-marketing surveillance and research are crucial for ensuring vaccine safety and effectiveness, aiding public health planning. Methods: Our retrospective cohort study included Albertans five years and older and vaccinated with at least one dose of an approved COVID-19 vaccine between 14 December 2020 and 30 April 2022. This epidemiological study aimed to determine the incidence of reported adverse events following immunization (AEFI) in Alberta and identify associated risk factors. Results: The study included 3,527,106 vaccinated Albertans who met the study inclusion criteria. A total of 2541 individuals (72.0 per 100,000) reported an AEFI, with 2759 adverse events, most of which occurred following the first dose of vaccine and within the first week post-vaccination. Of these, 70.4% were female, and the highest incidence was in the 35-54 age group. Given that mRNA vaccines were predominantly administered across Canada, we report AEFI rates (per 100,000 doses) for the mRNA vaccine brands at 27.7 for Pfizer and 40.7 for Moderna. Allergic events were the most frequently reported AEFI, followed by adenopathy. Logistic regression analysis indicated that sex (with females at higher risk), presence of comorbidities, days to symptom onset, vaccine type (mRNA vs. mixed doses), and the number of doses were significant factors associated with an AEFI event. Conclusions: Our study provides valuable information to guide policies surrounding COVID-19 vaccination. While the risk of serious adverse events was low in the population-based sample, further research is warranted to identify and investigate other possible risk factors that are still unknown.

Background/objectives: The emergence of the Omicron variant has complicated COVID-19 control and prompted vaccine updates. Recent studies have shown that a fourth dose significantly protects against infection and severe disease, though long-term immunity data remain limited. This study aimed to assess Anti-S-RBD antibodies and interferon-γ levels in healthcare workers 12 months after receiving bivalent Original/Omicron BA.4-5 fourth SARS-CoV-2 vaccine.

Methods: In this prospective cohort study, 549 healthcare workers were categorized by the initial vaccination schedule, with 229 individuals having received the fourth SARS-CoV-2 vaccine dose. Blood samples were collected from all participants 12 months post-vaccination.

Results: Significant differences in Anti-S-RBD antibody levels were observed between those receiving a fourth dose and those who did not, while no differences were seen in interferon-γ levels. After 12 months, there were no significant differences in humoral and cellular immunity response between volunteers primoinfected or reinfected across different periods by the Omicron variant. A multivariable analysis revealed an association between high antibody levels (>6000 U/mL) and interferon-γ levels (OR: 3.13; 95% CI: 1.3-7.7; p < 0.05). Regarding primary vaccine schedules, participants vaccinated with ChAdOx1 (a single or double dose) had notably lower antibody levels compared to those who received mRNA-based vaccines. Additionally, the study shows a higher frequency of multiple infections among those with a single-dose ChAdOx1 primary schedule (OR: 6.24; 95% CI: 1.25-31.15; p < 0.01).

Conclusions: Overall, mRNA-based vaccines exhibited stronger long-term immunogenicity. Repeated exposure to the Omicron variant seems to mitigate immune imprinting from the wild-type SARS-CoV-2. An association was observed between high antibody levels and a strong cellular response, although the correlation was not linear.

Background/Objectives: Vaccine hesitancy among immunocompromised patients is complex and not well understood. This study aimed to determine the rate of COVID-19 vaccine hesitancy among pediatric oncology and bone marrow transplant (BMT) patients and to understand associated factors. Methods: Parents of patients (≤18 years) with cancer or post-BMT completed the Parent Attitudes about Childhood Vaccines Survey. A COVID-19 vaccine hesitancy score (VHS-COVID) was calculated from 0 to 100 (higher scores indicating increasing hesitancy). A small group of patients (patients older than 15 years) were also surveyed directly. Results: Among 113 parent respondents, the majority were female (58%) and at least college/university educated (78%). The majority (73%) of patients had cancer (61% leukemia/lymphoma, 37% solid/CNS tumors), while 27% had received BMT for malignant and non-malignant conditions. Only 48% of patients had been vaccinated against COVID-19, compared to 88% of parents. Ineligibility due to phase of cancer/BMT treatment (27%), vaccine hesitancy (24%), and age (24%) were the top three reasons for not vaccinating against COVID-19. Only 13% of parents said they would "definitely vaccinate" if their child became eligible. VHS-COVID scores were higher for parents of patients in surveillance versus active therapy (mean 61 vs. 48; p = 0.03). Parents who had received fewer COVID-19 vaccine doses (0-1 vs. ≥2) were more hesitant toward all vaccines (p = 0.0002), COVID-19 vaccines (p = 0.0003), and influenza vaccines (p = 0.005). Conclusions: Vaccine hesitancy is common among this population and was demonstrated through beliefs (hesitancy scores) as well as vaccine uptake. Future work should focus on education targeting vaccine eligibility and engaging with vaccine hesitant families in the immunocompromised community.

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation, and promiscuity in incorporating foreign glycoproteins into its virions.

Methods: In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity, and efficacy in C57BL/6, Ifnar^-/-, and AG129 mice.

Results: We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of wild type (C57BL/6) and Ifnar^-/- mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection in a lethal SFTSV challenge model. Additionally, passive transfer of sera from immunized Ifnar^-/- mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects AG129 mice against challenge with the closely related Heartland bandavirus despite negligible neutralizing titers to the virus.

Conclusions: Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate for SFTSV and Heartland bandavirus with a favorable safety profile.

Multidrug-resistant tuberculosis (MDR-TB) poses a significant global health threat, especially when it involves the central nervous system (CNS). Tuberculous meningitis (TBM), a severe manifestation of TB, is linked to high mortality rates and long-term neurological complications, further exacerbated by drug resistance and immune evasion mechanisms employed by Mycobacterium tuberculosis (Mtb). Although pulmonary TB remains the primary focus of research, MDR-TBM introduces unique challenges in diagnosis, treatment, and patient outcomes. The effectiveness of current treatments is frequently compromised by poor CNS penetration of anti-TB drugs and the necessity for prolonged therapy, which often involves considerable toxicity. This review explores the potential of cytokine-based adjunct immunotherapies for MDR-TBM, addressing the challenges of balancing pro-inflammatory and anti-inflammatory signals within the CNS. A central focus is the prospective role of glutathione, not only in reducing oxidative stress but also in enhancing host immune defenses against Mtb's immune evasion strategies. Furthermore, the development of vaccines aimed at upregulating glutathione synthesis in macrophages represents a promising strategy to bolster the immune response and improve treatment outcomes. By integrating glutathione and innovative vaccine approaches into MDR-TBM management, this review proposes a comprehensive strategy that targets Mtb directly while supporting immune modulation, with the potential to enhance patient outcomes and reduce treatment related adverse effects. We underscore the urgent need for further research into adjunctive therapies and immunomodulatory strategies to more effectively combat MDR-TBM.

The research conducted in this preclinical study assesses QazCovid-live, a live attenuated COVID-19 vaccine created in Kazakhstan, by conducting preclinical evaluations of safety, immunogenicity, and allergenicity in various animal models, including mice, rats, hamsters, and guinea pigs. The vaccine, developed by attenuating SARS-CoV-2 via numerous Vero cell passages, had no significant adverse effects in acute and subacute toxicity assessments, even at elevated dosages. Allergenicity testing indicated the absence of both immediate and delayed hypersensitivity reactions. Immunogenicity evaluations revealed strong virus-neutralizing antibody responses, especially following intranasal and intratracheal delivery. Studies on reversibility and transmission further validated the vaccine's stability and non-pathogenicity. The data indicate that QazCovid-live is safe, immunogenic, and prepared for clinical trials, presenting a potential strategy for COVID-19 prevention.