Vaccines最新文献

Background: Nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) have emerged as a promising vaccine strategy, especially for COVID-19. While the LNPs protect mRNA from degradation and efficiently deliver the mRNA to antigen-presenting cells, the effect of lipid composition on the immunogenicity and protective efficacy of mRNA/LNP vaccines is not well characterized. Studies on using the mRNA/LNP platform for vaccines have largely focused on the nucleic acid cargo with less attention paid to the LNP vehicle. Whether the composition and biophysical properties of LNPs impact vaccine performance remains to be fully elucidated.

Methods: In the present study, we used SARS-CoV-2 Spike-mRNA as a prototype vaccine to study the effect of four different LNPs with various lipid compositions.

Results: We demonstrate that when the same Spike-mRNA was delivered in the LNP4 formulation based on phospholipid 1,2-dioleoyl-sn-glycero-3-Phosphoethanolamine, it outperformed other LNPs (LNP1, LNP2, and LNP3) that are based on different lipids. Compared to the other three LNPs, LNP4 (i) enhanced the phenotypic and functional maturation of dendritic cells; (ii) induced strong T-cell responses; (iii) increased the secretion of proinflammatory cytokines and pro-follicular T helper (Tfh) cell cytokines; (iv) induced higher neutralization IgG titers; and (v) provided better protection against SARS-CoV-2 infection and COVID-19-like symptoms in the hamster model. Furthermore, we compared LNP-4 with the commercially available LNPs and found it to provide better T-cell immunity against COVID-19 in hamsters.

Conclusion: This study suggests mRNA vaccines encapsulated in Phospholipid 1,2-Dioleoyl-sn-Glycero-3-PhosphoEthanolamine containing LNPs induced Potent B- and T cell immunity. The mechanisms by which Phospholipid 1,2-Dioleoyl-sn-Glycero-3-PhosphoEthanolamine-based LNPs may activate protective B and T cells are discussed.

Background: Equine herpesvirus type 1 (EHV1) is a ubiquitous viral pathogen infecting the equine population worldwide. EHV1 infection causes respiratory illness, abortion, neonatal foal mortality, and myeloencephalopathy. The currently available modified live EHV1 vaccines have safety and efficacy limitations. The two mutant EHV1 viruses (vToH-DMV (∆IR6/gE) and vToH-QMV (∆IR6/UL43/gE/UL56)), generated by the deletion of genes responsible for virulence (gE and IR6) and immunosuppression (uL43 and uL56), have been previously characterized by our group and found to generate good immune responses. The present study aimed to determine the safety and protective efficacy of the above mutants against a virulent EHV1 challenge in a murine model.

Methods: BALB/c mice were intranasally immunized with a live vToH-QMV or vToH-DMV vaccine. Intranasal booster immunization was given at 14 days post-vaccination (dpv). Both mutants induced an optimal level of EHV1-specific humoral and cell-mediated immune responses, as determined by virus neutralization assay, ELISA, and immunophenotyping. At 35 dpv, the mice were intranasally challenged with wild-type EHV1 (vRaj strain).

Results: Amongst the two mutants, vToH-QMV induced a better immune response than the vToH-DMV vaccine. Furthermore, vToH-QMV provided good protection in mice against the virulent challenge. It specifically exhibited less severe clinical disease in terms of clinical signs, body weight reduction, and gross and histopathological lung lesions accompanied by early virus clearance.

Conclusions: These studies are suggestive of vToH-QMV EHV1 being a potential vaccine candidate against EHV1 infection, which needs to be finally tested in the main host, i.e., horses.

Background: Very-low-birth-weight infants (VLBWIs; birth weight < 1500 g) are at an increased risk of complicated influenza infection, which frequently includes pneumonia, encephalitis or even death. Data on influenza immunization and its outcome in VLBWIs are scarce. This study aimed to provide epidemiological data on influenza immunization for German VLBWIs and hypothesized that immunization would protect VLBWIs from infection-mediated neurodevelopmental impairment and preserves lung function at early school age.

Methods: In this observational population-based German Neonatal Network (GNN) study, infants born between 2009 and 2015 were invited to partake in a 6-year follow-up investigation including lung function and developmental testing. Uni- and multivariate analyses were performed to evaluate the clinical characteristics and outcomes of influenza-immunized VLBWIs compared to non-immunized VLBWIs.

Results: Influenza immunization was performed in 871 out of the 3358 VLBWIs (26%) with six-year follow-up. Immunized infants were characterized by a low gestational age and higher rates of morbidity, particularly bronchopulmonary dysplasia. Although early immunization showed no safety signals and had protective effects on the long-term risk of bronchitis (OR: 0.2; CI: 0.1-0.6; p = 0.002), most VLBWIs (88.0%) were unimmunized in their first influenza season.

Conclusions: Influenza immunization was not associated with improved lung function (forced expiratory volume in one second and forced vital capacity) or a better neurocognitive outcome (intelligence quotient and strengths and difficulties questionnaire) at early school age. In Germany, only one quarter of 6-year-old VLBWIs were immunized against influenza, particularly those born <28 gestational weeks and/or BPD. Specific influenza immunization guidelines that define evidence-based recommendations are needed for this vulnerable group.

Background: SCTV01E is a tetravalent recombinant COVID-19 vaccine authorized for emergency use in China for adults 18 years and older but not for those under 18. Objective: This Phase 2 trial assessed the safety and immunogenicity of SCTV01E in healthy children and adolescents aged 3 to 17 years, to establish immunobridging with that observed in adults from the efficacy pivotal trial (NCT05308576). Methods: Participants were randomly assigned to receive either 30 µg of SCTV01E or a placebo. Primary endpoints were safety and immunogenicity focused on the geometric mean titer (GMT) and seroresponse rate (SRR) of neutralizing antibodies (nAb) against Omicron BA.5. Results: In total, 268 participants (214 SCTV01E vs. 54 placebo) were included in the safety analysis, with 241 participants (191 vs. 50) in the immunogenicity analysis. Overall, 127 (59.3%) participants receiving SCTV01E and 9 (16.7%) receiving a placebo reported adverse events (AEs), most of which were Grade 1 or 2. No serious adverse events (SAEs) or adverse events of special interest (AESIs) were reported. In the immunogenicity bridging analysis, data from 95 youths were compared with data from 188 adults; the geometric mean ratio (GMR) of the titers was 8.78 (95% CI: 6.05-12.74, p < 0.001), with the lower bound of the 95% CI exceeding 0.67. The difference in the SRR was 6.34% (95% CI: 0.93-11.22%) (p = 0.029), and the lower bound of the 95%CI was >-5%, indicating superiority. Conclusions: SCTV01E was found to be safe and well tolerated in children and adolescents, generating a robust immune response against Omicron BA.5. This supports its potential use in younger populations.

Vaccine hesitancy, which refers to the reluctance to be vaccinated, poses a major risk to public health in preventing infectious diseases. This hesitancy has been evident for many years, especially regarding childhood vaccines. The main factors contributing to this hesitancy include religious or personal beliefs, concerns about safety and efficacy, and desire to receive more information from healthcare providers. This literature review examines hesitancy regarding COVID-19 vaccines in different population segments in Turkey. Hesitancy rates and reasons in the general population and specific groups such as pregnant women, parents, healthcare workers and students were presented based on published research articles. Approximately half of the Turkish population declared their hesitancy towards COVID-19 vaccines. A negative correlation was found between vaccine hesitancy and health literacy. The relationship between COVID-19 vaccine hesitancy and religiosity was also investigated. Age is another factor affecting this vaccine hesitancy. Older age was shown to be correlated with positive attitude towards COVID-19 vaccination. Moreover, participants with positive attitudes towards other vaccines, those with chronic diseases and those with a personal history of COVID-19 were more likely to have positive perceptions of COVID-19 vaccines. Higher life satisfaction and non-smoking status were associated with a higher likelihood of COVID-19 vaccine acceptance. Increased scientific data on the efficacy and side effects of COVID-19 vaccines and more information from healthcare professionals would likely reduce the hesitancy towards COVID-19 vaccines.

Objective: We evaluate the immunotherapeutic potential of the yellow fever virus vaccine strain 17D (YFV 17D) for intratumoral therapy of pancreatic cancer in mice. Methods: The cytopathic effect of YFV 17D on mouse syngeneic pancreatic cancers cells were studied both in vitro and in vivo and on human pancreatic cancers cells in vitro. Results: YFV 17D demonstrated a strong cytopathic effect against human cancer cells in vitro. Although YFV 17D did not exhibit a lytic effect against Pan02 mouse cells in vitro, a single intratumoral administration of 17D caused a delay in tumor growth and an increase in median survival by 30%. Multiple injections of 17D did not further improve the effect on tumor growth; however, it notably extended the median survival. Furthermore, preliminary immunization with 17D enhanced its oncotherapeutic effect. Conclusions: Intratumoral administration of yellow fever virus vaccine strain 17D delayed tumor in a murine model of pancreatic cancer. The fact that YFV 17D in vitro affected human cancer cells much more strongly than mouse cancer cells appears promising. Hence, we anticipate that the in vivo efficacy of YFV-17D-based oncolytic therapy will also be higher against human pancreatic carcinomas compared to its effect on the mouse pancreatic tumor.

Background: Vaccination is one of the most effective ways of protecting individuals against serious infectious diseases and their fatal consequences.

Objectives: The aim of this scoping review was to synthesize data on parental attitudes toward vaccination and identify factors influencing the motivators and barriers to children's vaccination based on Polish studies.

Methods: The scoping review process and reporting were based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScRs) checklist. In the period between January 2014 and July 2024, the following databases were searched for publications: PubMed, Web of Science, Cochrane, Ebsco, and Scholar Google.

Results: A total of 1531 potentially relevant records were reviewed, and 30 original publications from research samples collected in Poland were selected. According to the findings, vaccination rates varied between 100% and 70%, with parental acceptance levels for mandatory vaccination ranging from 99% to 65%. Parents most commonly cited the physician, the nurse, and the Internet as their primary sources of vaccination-related information. Moreover, parental primary motivators for vaccinating their children were prevention against infectious diseases, the opinion that vaccines are safe, and the belief that childhood vaccination is right and effective. The major barriers to vaccination were fear of vaccine side effects and the belief that vaccines are ineffective. Parents that were better educated, were of younger age, lived in cities, and had a higher income were much more likely to vaccinate their children.

Conclusions: Understanding parental attitudes toward vaccination may help develop an educational program aimed at combating misinformation and increasing childhood vaccination coverage rates.

Background: Immunization plays a substantial role in reducing the under-five mortality rate. However, Tanzania still has a significant number of zero-dose and under-vaccinated children and was ranked among the top ten African countries with the highest numbers of zero-dose children in 2022. The human-centered design (HCD) approach is more ethical and effective at addressing public health challenges in complex sociocultural settings. This study aimed to use the HCD approach to aid in identifying, prioritizing, and implementing community-centric interventions in Tanzania, particularly in the Ilala District of Dar es Salaam, to increase vaccine demand and close the zero-dose gap by at least 50%. Methods: The study involved co-creation workshops with 483 participants to identify, design, and test solutions. The study followed the UNICEF Journey to Health and Immunization framework to identify barriers and enablers influencing stakeholders in adopting and sustaining health- and immunization-related actions. Results: The study identified the causes of under-five defaulting and the zero-dose gap, i.e., the inadequate support of local community leaders in under-five vaccination sensitization and surveillance; poor infrastructure to new settlement areas; hesitancy and unwillingness of parents/guardians; absence of house numbers; limited/time-constrained availability of resources to facilitate mobile immunization services, etc. The participants were able to come up with 309 ideas, which were refined through multiple iterations using the impact--effort matrix and skimmed down to three (3) solutions: (i) having health facilities to notify and alert local leaders about vaccination dates; (ii) using parents, kids, and grownups who got vaccinated to influence others; (iii) using local government leaders and house representatives for vaccine advocacy. Of these, the solution involving local government leaders and house representatives for vaccine advocacy was implemented. An advocacy strategy was used to enhance the collaboration of the District Commissioner, Council leaders, and community leaders. A home-to-home interpersonal sensitization approach accompanied by the household delivery of vaccination services was employed. The findings reveal that the HCD framework was impactful in increasing collaborations/cooperation with local government leaders and community ownership of the under-five vaccination initiative. As a result, 67,145 houses, equal to 104%, were reached, surpassing the initial target of 64,800 houses, and 131,088 families, equal to 83% of the targeted 156,995 households, were sensitized through a home-to-home campaign approach. This study demonstrates the effectiveness of the approach. Researchers and practitioners are encouraged to adopt the HCD approach when addressing public health challenges, especially in complex sociocultural settings.

Background: Botulinum neurotoxins (BoNTs), produced by Clostridium botulinum, are potent protein toxins that can cause botulism, which leads to death or neuroparalysis in humans by targeting the nervous system. BoNTs comprise three functional domains: a light-chain enzymatic domain (LC), a heavy-chain translocation domain (HC_N), and a heavy-chain receptor-binding domain (HC_C). The HC_C domain is critical for binding to neuronal cell membrane receptors and facilitating BoNT internalization via endocytosis. Accordingly, it may serve as a vaccine candidate, inducing anti-BoNT-neutralizing antibodies in animals. Here, we aimed to develop a vaccine capable of simultaneously defending against both BoNT/A and B.

Methods: We combined the HC_C domains of botulinum neurotoxin type A (BoNT/A) and botulinum neurotoxin type B (BoNT/B) in Escherichia coli to produce a recombinant protein (rHC_CB-L-HC_CArHCcB) that offers dual protection against both toxins by inhibiting their receptor binding. To evaluate the efficacy of the vaccine, mice were immunized intramuscularly with rHC_CB-L-HC_CA plus alum thrice at 2-week intervals, followed by the assessment of immunogenicity and protective efficacy.

Results: The antibody titer in mice immunized with rHC_CB-L-HC_CA was significantly higher than that in mice immunized with alum alone, protecting them from the lethal challenges of BoNT/A (10⁵ 50% lethal dose, LD₅₀) and B (10³ LD₅₀).

Conclusion: These findings suggest that rHC_CB-L-HC_CA may simultaneously be an effective vaccine candidate against BoNT/A and B.

Background/objectives: Vaccines have been recognized as one of the most effective public health interventions. However, vaccine-associated anaphylaxis, although rare, is a serious adverse reaction. The incidence of anaphylaxis related to non-COVID-19 vaccines in adults remains underreported. This systematic review and meta-analysis aim to estimate the incidence of post-vaccination anaphylaxis across various vaccines in adults.

Methods: A comprehensive literature search of PubMed, Embase, Scopus, and Web of Science identified studies on anaphylaxis following vaccination in adults (≥18 years), excluding COVID-19 vaccines. PRISMA 2020 guidelines were followed. The protocol was registered in PROSPERO in advance (ID CRD42024566928). Random-effects and fixed-effects models were used to pool data and estimate the logit proportion, with the logit-transformed proportion serving as the effect size, thereby allowing for the calculation of event rates.

Results: A total of 37 studies were included in the systematic review, with 22 studies contributing to the meta-analysis, representing a combined population of 206,855,261 participants. Most studies focused on influenza vaccines (n = 15). Across all studies, 262 anaphylactic cases were reported, with 153 cases related to influenza vaccines, followed by herpes zoster virus vaccines (38 cases) and yellow fever vaccines (29 cases). Td/Tdap vaccine had the lowest rate (0.0001 per 100,000 participants). The overall random-effects model yielded a logit proportion of -10.45 (95% CI: -12.09 to -8.82, p < 0.001), corresponding to an event rate of 2.91 events per 100,000 subjects (95% CI: 0.56 to 14.73). Sensitivity analysis showed a higher incidence for influenza, hepatitis vaccines, and in vulnerable populations.

Conclusions: Anaphylaxis following vaccination in adults is rare but varies by vaccine type. Strengthened monitoring and preparedness are essential, especially in non-medical settings, to ensure a rapid response to anaphylaxis and maintain public confidence in vaccination programs.