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Robust and sustained immunity in beagles following one single nasal administration of H3N2 canine influenza virus-like particle 小猎犬在单次鼻腔注射H3N2犬流感病毒样颗粒后产生强大和持续的免疫
IF 2.2 Q3 IMMUNOLOGY Pub Date : 2025-10-16 DOI: 10.1016/j.jvacx.2025.100739
Fei-fei Ge , Li-ping Shen , De-quan Yang, Hai-xiao Shen, Xin Li, Jian Liu, Jian Wang, Hongjin Zhao
In this study, we used baculovirus to express hemagglutinin (HA) and neuraminidase (NA) to prepare a novel genotype of H3N2 canine influenza virus particles (VLPs). The effectiveness of the H3N2 VLP vaccine was evaluated by detecting HI antibodies, the antiviral protection rate, antibody persistence and anatomical examination of the lungs.A challenge model has been established in a previous study for the study of canine influenza virus-like particle vaccines. A/Canine/Shanghai/0103/2019, with a challenge dose of 106 EID50, infects 10-week-old healthy beagle dogs through nasal instillation and can cause severe clinical symptoms. Using a single dose of VLP vaccine for beagle dogs, the vaccine was tested at titers of 26 intranasally and 26 intramuscularly. One week after a single immunization, the HI titer promptly reached 28 among the immunized groups. The duration of antibody can persist for four months. We differentiated between CD4+ and CD8+ T cells in the peripheral blood. Four weeks after the single immunization, all beagles except those in the noninfected and nonimmunized groups were intranasally challenged with live H3N2 virus (1 × 106 EID50). All immunized beagles shed no virus at d 1–4 post-challenge. After the challenge, the placebo control beagles shed the virus on d 1 post-challenge (105.85±0.071 EID50). An anatomical examination of the lungs revealed that visible lesions were rarely detected in the lungs of the nasal immunization group, and the lungs were as healthy as those of the noninfected and nonimmunized groups were. The lung surfaces presented visible bleeding spots in the intramuscular immunization group and placebo-control group. Their effectiveness will provide a scientific basis for the promotion and use of these products.
本研究利用杆状病毒表达血凝素(HA)和神经氨酸酶(NA),制备了新型H3N2犬流感病毒颗粒(VLPs)。通过检测H3N2 VLP疫苗的HI抗体、抗病毒保护率、抗体持久性和肺部解剖检查来评价疫苗的有效性。在先前的一项研究中,已经建立了一个攻击模型,用于研究犬流感病毒样颗粒疫苗。A/Canine/Shanghai/0103/2019的攻毒剂量为106 EID50,通过鼻腔注入感染10周龄的健康比格犬,并可引起严重的临床症状。使用比格犬的单剂量VLP疫苗,测试了26滴鼻内和26滴肌肉注射疫苗。单次免疫后一周,免疫组的HI滴度迅速达到28。抗体持续时间可达4个月。我们将外周血中的CD4+ T细胞和CD8+ T细胞区分开来。单次免疫4周后,除未感染组和未免疫组外,所有比格犬均经鼻感染H3N2活病毒(1 × 106 EID50)。所有免疫的小猎犬在攻击后1-4天没有病毒脱落。攻毒后,安慰剂对照的小猎犬在攻毒后第1天排出病毒(105.85±0.071 EID50)。肺部解剖检查显示,鼻腔免疫组肺部很少发现明显病变,肺部与未感染和未免疫组一样健康。肌注免疫组和安慰剂对照组肺表面出现明显的出血斑点。其有效性将为这些产品的推广和使用提供科学依据。
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引用次数: 0
Real-world effectiveness of hepatitis B vaccination in dialysis patients 乙型肝炎疫苗在透析患者中的实际有效性
IF 2.2 Q3 IMMUNOLOGY Pub Date : 2025-10-15 DOI: 10.1016/j.jvacx.2025.100738
Giovanni Genovese , Elisabetta Genovese , Domenico Santoro , Flavia Pennisi , Giuseppe Trimarchi , Raffaele Squeri , Daniela Lo Giudice , Cristina Genovese

Background

Chronic kidney disease is (CKD) a highly prevalent condition worldwide, with an increasing prevalence in the general population. Effective vaccination strategies are crucial in this population to prevent hepatitis B virus (HBV)-related complications. This study aimed to evaluate the effectiveness of different HBV vaccines in patients with CKD undergoing dialysis, focusing on seroconversion rates and overall immune response.

Methods

A non-concurrent prospective cohort study was conducted on 160 outpatient long-term dialysis patients at the G. Martino Hospital in Messina. Patients were vaccinated with either FENDRIX (HB-AS04), HBVAXPRO 40 mg, or a combination, and their immune responses were assessed one month after the completion of the vaccination course.

Results

The study achieved 100 % vaccination coverage. The overall seroconversion rate was 62.5 %, with mean anti-HBs titers of 604.15 mIU/mL (±437.23 SD) across the cohorts. No significant differences were observed between responders and non-responders concerning demographic, clinical, and biochemical characteristics.

Conclusion

The study confirms the effectiveness of HBV vaccines in patients with CKD, though with a lower and delayed response compared to the general population. Establishing a diagnostic-therapeutic care pathway that integrates vaccination from the early stages of CKD is essential to improve outcomes in this high-risk group.
背景:慢性肾脏疾病(CKD)在世界范围内是一种高度流行的疾病,在普通人群中的患病率越来越高。有效的疫苗接种策略对于预防乙肝病毒相关并发症至关重要。本研究旨在评估不同HBV疫苗在CKD透析患者中的有效性,重点关注血清转化率和总体免疫反应。方法对墨西拿市G. Martino医院160例门诊长期透析患者进行非同期前瞻性队列研究。患者分别接种了FENDRIX (HB-AS04)、HBVAXPRO 40 mg或两者的联合疫苗,并在疫苗接种过程完成一个月后评估他们的免疫反应。结果该研究实现了100%的疫苗接种覆盖率。总体血清转化率为62.5%,整个队列的平均抗hbs滴度为604.15 mIU/mL(±437.23 SD)。反应者和无反应者在人口学、临床和生化特征方面无显著差异。结论:该研究证实了HBV疫苗在CKD患者中的有效性,尽管与一般人群相比,其反应较低且延迟。建立一个诊断-治疗的护理途径,整合早期阶段的CKD疫苗接种,对于改善这一高危人群的预后至关重要。
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引用次数: 0
Effectiveness of 2023–2024 mRNA-1273 XBB.1.5 vaccine against COVID-19 associated hospitalizations and medically attended COVID-19 in the United States 2023-2024 mRNA-1273 XBB.1.5疫苗在美国预防COVID-19相关住院和就医的有效性
IF 2.2 Q3 IMMUNOLOGY Pub Date : 2025-10-15 DOI: 10.1016/j.jvacx.2025.100737
Zhe Zheng , Mitra Yousefi , Danielle MacCormac , Jennifer M. Radin , Tianyu Sun , Amanda Wilson , Rohan Shah , Michelle Skornicki , Paige Sheridan , Astra Toyip , Katherine Mues , Daina Esposito , Andre Araujo , Evan Anderson

Background

COVID-19 remains a public health concern, causing an estimated 50,000 deaths and 827,000 hospitalizations in the United States during the 2023–2024 season. As SARS-CoV-2 continues to evolve, assessing COVID-19 vaccine effectiveness (VE) remains essential. This study evaluated the effectiveness of Moderna's 2023–2024 mRNA-1273 vaccine formulation targeting the XBB.1.5 variant in preventing COVID-19 associated hospitalizations and medically attended COVID-19 in the US.

Methods

This non-interventional, matched retrospective cohort study used US administrative claims data (September 2023–February 2024). Individuals vaccinated with mRNA-1273 XBB.1.5 were matched to individuals who did not receive an updated 2023–2024 COVID-19 vaccine. COVID-19 associated hospitalizations and medically attended COVID-19 outcomes were identified 7 days after the index date. Subpopulations of interest included age group, immunocompromised individuals, and those received a BA.4/BA.5 vaccine in the prior season. VE was estimated using 1 minus hazard ratios.

Results

Among 900,194 mRNA-1273 vaccinated and matched unexposed individuals, median follow-up for COVID-19 associated hospitalizations was 111 days (vaccinated) and 99 days (unexposed). Overall, VE against COVID-19 associated hospitalizations was 56 % (95 % CI: 52 %–60 %). VE ranged from 52 % (95 % CI: 43 %–59 %) in immunocompromised individuals to 62 % (95 % CI: 35 %–78 %) in those aged 50–64 years. For medically attended COVID-19, VE was 24 % (95 % CI: 22 %–25 %).

Conclusions

mRNA-1273 XBB.1.5 demonstrates significant incremental protection against COVID-19 associated hospitalizations and medically attended COVID-19 relative to those who did not receive 2023–2024 COVID-19 vaccination. These findings reinforce the need for vaccination efforts to reduce the burden of COVID-19.
2019冠状病毒病仍然是一个公共卫生问题,在2023-2024年期间,美国估计有5万人死亡,82.7万人住院。随着SARS-CoV-2的不断演变,评估COVID-19疫苗的有效性仍然至关重要。本研究评估了Moderna针对XBB.1.5变异的2023-2024 mRNA-1273疫苗制剂在美国预防COVID-19相关住院和就医的有效性。方法这项非干预性、匹配的回顾性队列研究使用了美国行政索赔数据(2023年9月- 2024年2月)。接种mRNA-1273 XBB.1.5疫苗的个体与未接种更新的2023-2024 COVID-19疫苗的个体相匹配。在索引日期后7天确定与COVID-19相关的住院情况和就医的COVID-19结局。感兴趣的亚群包括年龄组、免疫功能低下的个体和接受BA.4/BA的个体。5疫苗在前一个季节。使用1 -风险比估计VE。结果900,194名接种mRNA-1273疫苗和匹配的未暴露者中,与COVID-19相关的住院随访中位数为111天(接种者)和99天(未暴露者)。总体而言,与COVID-19相关的住院率为56% (95% CI: 52% - 60%)。免疫功能低下个体的VE范围为52% (95% CI: 43% - 59%), 50-64岁人群的VE范围为62% (95% CI: 35% - 78%)。对于就医的COVID-19, VE为24% (95% CI: 22% - 25%)。结论与未接种2023-2024年COVID-19疫苗的人群相比,smrna -1273 XBB.1.5对COVID-19相关住院和就医的保护作用显著增加。这些发现进一步表明,有必要开展疫苗接种工作,以减轻COVID-19的负担。
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引用次数: 0
Immunogenicity of five Encapsidated DENV antigens supports their potential as a safe and protective subunit vaccine candidate 五种囊化DENV抗原的免疫原性支持它们作为安全和保护性亚单位候选疫苗的潜力
IF 2.2 Q3 IMMUNOLOGY Pub Date : 2025-10-14 DOI: 10.1016/j.jvacx.2025.100740
Mathurin Seesen , Tuksin Jearanaiwitayakul , Nattika Nantachit , Phissinee Jakaew , Jitra Limthongkul , Panya Sunintaboon , Sukathida Ubol
Dengue virus infection continues to pose a major global health challenge, affecting approximately 3.9 billion individuals annually. Unfortunately, the efficacy and safety profiles of currently licensed dengue vaccines remain debatable. This highlights the need for a next-generation vaccine that provides protection against all DENV serotypes. In this study, the immunogenicity of five DENV proteins was evaluated, including the envelope domain III proteins of all four dengue virus serotypes and C-terminally truncated NS1 protein of DENV-2, loaded into N, N, N-trimethyl chitosan nanoparticles. We demonstrated, here, that sequential immunization with these encapsidated immunogens elicited antibody responses known to correlate with protection against all four DENV serotypes. These responses facilitated the elimination of both infected cells and virus particles through a multifaceted mechanism. Moreover, the immunization induced functional cytotoxic T cell responses to all tested immunogens. These findings indicate that immunization with the designed immunogens induces robust and protective immune responses against all four DENV serotypes. This form of immunogens offers a promising, safe and effective subunit dengue vaccine candidate.
登革热病毒感染继续对全球健康构成重大挑战,每年影响约39亿人。不幸的是,目前获得许可的登革热疫苗的有效性和安全性仍然存在争议。这突出表明需要一种能够针对所有DENV血清型提供保护的下一代疫苗。本研究评估了5种DENV蛋白的免疫原性,包括所有4种登革热病毒血清型的包膜结构域III蛋白和DENV-2的c端截断NS1蛋白,并将其加载到N, N, N-三甲基壳聚糖纳米颗粒中。在这里,我们证明了用这些封装的免疫原进行顺序免疫可引起抗体反应,这些抗体反应已知与针对所有四种DENV血清型的保护相关。这些反应通过多方面的机制促进了被感染细胞和病毒颗粒的消除。此外,免疫诱导功能性细胞毒性T细胞应答所有测试的免疫原。这些结果表明,用设计的免疫原免疫可诱导针对所有四种DENV血清型的强效和保护性免疫应答。这种形式的免疫原提供了一种有前途的、安全有效的登革热亚基候选疫苗。
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引用次数: 0
A meta-analysis of digital interventions to reduce vaccination-related pain in children 减少儿童接种疫苗相关疼痛的数字干预措施的荟萃分析
IF 2.2 Q3 IMMUNOLOGY Pub Date : 2025-10-13 DOI: 10.1016/j.jvacx.2025.100736
Kevin E. Tololiu , Arie A. Kurnianto , Wirda Y. Dulahu , Ferenc Kocsor , Krisztina Csokasi

Background

Despite the effectiveness of vaccination in decreasing the mortality rate, pain related to needle procedures contribute to the children's incompliance vaccination uptake. Digital technology, as a widely used distracting tool, requires investigation for its efficacy and consistency. This study aims to see and compare the effectiveness of each digital intervention in reducing pain in children's vaccination.

Method

A systematic review and meta-analysis were conducted from five databases: Cochrane Library, APAPsychNet, Embase, EBSCO, and PubMed from June to September 2024. Two group trials using any digital intervention to reduce children's vaccination pain were included. A classical meta-analysis using random effects was applied to measure the effect size of pain level between intervention and control for overall and per category of digital interventions.

Result

11 of 1665 records were analysed. Digital intervention showed an overall pain education during vaccination (SMD = −0.54, 95 % CI: −1.06, −0.02, I2 = 92.2 %, P = 0.04). All groups, including robots and mobile/computer technologies, showed more pain reduction than the control group. However, only virtual reality studies showed a statistically significant difference (SMD = −0.74, 95 % CI: −1.41, −0.08, I2 = 88.4 %, P = 0.03).

Conclusion

Digital interventions have enormous potential in reducing needle-related pain. While virtual reality has a prominent effect due to its immersive nature, robots have viable efficacy by considering the interaction and realistic presentation. Mobile technologies' flexibility enables customization to children's needs and synergy with combined interventions.
背景:尽管疫苗接种在降低死亡率方面是有效的,但与注射针头相关的疼痛是儿童不遵守疫苗接种的原因之一。数字技术作为一种被广泛使用的分散注意力的工具,其有效性和一致性需要研究。本研究旨在观察和比较每种数字干预在减少儿童接种疫苗疼痛方面的有效性。方法对2024年6 - 9月Cochrane Library、APAPsychNet、Embase、EBSCO和PubMed 5个数据库进行系统评价和meta分析。包括两组使用任何数字干预来减少儿童接种疫苗疼痛的试验。采用随机效应的经典荟萃分析来测量干预和控制之间总体和每个类别数字干预的疼痛水平的效应大小。结果对1665份病历进行分析。数字干预显示疫苗接种期间的整体疼痛教育(SMD = - 0.54, 95% CI: - 1.06, - 0.02, I2 = 92.2%, P = 0.04)。所有小组,包括机器人和移动/计算机技术,都比对照组表现出更多的疼痛减轻。然而,只有虚拟现实研究显示有统计学意义的差异(SMD = - 0.74, 95% CI: - 1.41, - 0.08, I2 = 88.4%, P = 0.03)。结论数字化干预在减少针刺相关疼痛方面具有巨大的潜力。虚拟现实因其沉浸性而具有突出的效果,而机器人从交互性和逼真的呈现来看具有可行的功效。移动技术的灵活性可以根据儿童的需求进行定制,并与综合干预措施协同作用。
{"title":"A meta-analysis of digital interventions to reduce vaccination-related pain in children","authors":"Kevin E. Tololiu ,&nbsp;Arie A. Kurnianto ,&nbsp;Wirda Y. Dulahu ,&nbsp;Ferenc Kocsor ,&nbsp;Krisztina Csokasi","doi":"10.1016/j.jvacx.2025.100736","DOIUrl":"10.1016/j.jvacx.2025.100736","url":null,"abstract":"<div><h3>Background</h3><div>Despite the effectiveness of vaccination in decreasing the mortality rate, pain related to needle procedures contribute to the children's incompliance vaccination uptake. Digital technology, as a widely used distracting tool, requires investigation for its efficacy and consistency. This study aims to see and compare the effectiveness of each digital intervention in reducing pain in children's vaccination.</div></div><div><h3>Method</h3><div>A systematic review and meta-analysis were conducted from five databases: Cochrane Library, APAPsychNet, Embase, EBSCO, and PubMed from June to September 2024. Two group trials using any digital intervention to reduce children's vaccination pain were included. A classical meta-analysis using random effects was applied to measure the effect size of pain level between intervention and control for overall and per category of digital interventions.</div></div><div><h3>Result</h3><div>11 of 1665 records were analysed. Digital intervention showed an overall pain education during vaccination (SMD = −0.54, 95 % CI: −1.06, −0.02, I<sup>2</sup> = 92.2 %, <em>P</em> = 0.04). All groups, including robots and mobile/computer technologies, showed more pain reduction than the control group. However, only virtual reality studies showed a statistically significant difference (SMD = −0.74, 95 % CI: −1.41, −0.08, I<sup>2</sup> = 88.4 %, <em>P</em> = 0.03).</div></div><div><h3>Conclusion</h3><div>Digital interventions have enormous potential in reducing needle-related pain. While virtual reality has a prominent effect due to its immersive nature, robots have viable efficacy by considering the interaction and realistic presentation. Mobile technologies' flexibility enables customization to children's needs and synergy with combined interventions.</div></div>","PeriodicalId":43021,"journal":{"name":"Vaccine: X","volume":"27 ","pages":"Article 100736"},"PeriodicalIF":2.2,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145325795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fatal measles complication in the misinformation era: A case of catastrophically rapid SSPE in an unvaccinated child 错误信息时代的致命麻疹并发症:一例未接种疫苗儿童的灾难性快速SSPE
IF 2.2 Q3 IMMUNOLOGY Pub Date : 2025-09-30 DOI: 10.1016/j.jvacx.2025.100733
Ali Manafi Anari , Ladan Teymoorzadeh , Ramez Nasiri , Sajjad Narimani
Vaccine hesitancy, amplified by digital misinformation, represents a growing threat to global health. This case demonstrates its lethal consequences through rapid-onset subacute sclerosing panencephalitis (SSPE) in an unvaccinated 3.5-year-old girl whose parents refused measles-mumps-rubella (MMR) vaccination due to pandemic-amplified misinformation. A developmentally normal preschooler, vaccinated only at birth (BCG, oral polio vaccine, and hepatitis B vaccine), presented with head-drop seizures progressing to myoclonus and speech loss within weeks. Comprehensive diagnostic workup confirmed SSPE through fulfillment of Dyken's criteria, including characteristic clinical presentation, elevated measles-specific IgG in both CSF (titer 1:256 by ELISA) and serum (titer 1:128) with elevated CSF/serum antibody index (1.8), periodic complexes on EEG, symmetric white matter lesions on MRI, and exclusion of alternative infectious/autoimmune etiologies. Despite immunomodulatory therapy (intravenous immunoglobulins and ribavirin), she progressed to vegetative state by week 12, expiring at 4 months post-onset. Parental refusal of both vaccination and life-saving interventions reflected profound medical mistrust. Neuroimaging revealed rapid progression to diffuse atrophy within 6 weeks. MR spectroscopy showed marked reduction in N-acetylaspartate (NAA) and elevated lactate. This progression from symptom onset to death in 4 months represents one of the most rapid SSPE courses documented, highlighting the vulnerability of unvaccinated children and demonstrating how digital misinformation enables preventable tragedies. The case demands: (1) nuanced strategies to combat health misinformation, (2) heightened vigilance for fulminant SSPE in unvaccinated children, and (3) urgent reinforcement of measles vaccination programs. When vaccination rates decline, children become the tragic casualties of misinformation.
对疫苗的犹豫,再加上数字上的错误信息,对全球健康构成了日益严重的威胁。该病例通过一名未接种疫苗的3.5岁女孩的快速发作亚急性硬化性全脑炎(SSPE)证明了其致命后果,该女孩的父母由于大流行放大的错误信息而拒绝接种麻疹-腮腺炎-风疹(MMR)疫苗。发育正常的学龄前儿童,出生时仅接种疫苗(卡介苗、口服脊髓灰质炎疫苗和乙型肝炎疫苗),在数周内出现头滴发作进展为肌阵挛和语言丧失。通过满足Dyken的标准,全面的诊断工作证实SSPE,包括特征性的临床表现,脑脊液(ELISA滴度1:6 6 6)和血清(滴度1:128)中麻疹特异性IgG升高,脑脊液/血清抗体指数升高(1.8),脑电图周期性复合体,MRI对称白质病变,以及排除其他感染/自身免疫性病因。尽管免疫调节治疗(静脉注射免疫球蛋白和利巴韦林),她在第12周进展为植物人状态,在发病后4个月死亡。父母拒绝接种疫苗和挽救生命的干预措施反映了深刻的医疗不信任。神经影像学显示6周内迅速发展为弥漫性萎缩。磁共振光谱显示n -乙酰天冬氨酸(NAA)明显减少,乳酸升高。这种从症状发作到死亡的4个月内的进展是有记录的SSPE最快速的过程之一,突出了未接种疫苗儿童的脆弱性,并表明数字错误信息如何使可预防的悲剧成为可能。该病例要求:(1)采取细致入微的策略来打击健康错误信息;(2)提高对未接种疫苗的儿童的暴发性SSPE的警惕;(3)紧急加强麻疹疫苗接种计划。当疫苗接种率下降时,儿童就会成为错误信息的悲惨受害者。
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引用次数: 0
Current landscape and challenges in adjuvant and antigen delivery systems for vaccine 疫苗佐剂和抗原递送系统的现状和挑战
IF 2.2 Q3 IMMUNOLOGY Pub Date : 2025-09-29 DOI: 10.1016/j.jvacx.2025.100735
Xiaoyi Fu
Vaccines have emerged as a prominent strategy for the prevention and treatment of diseases. Adjuvants, as immune enhancers and delivery systems, play a crucial role in improving the efficiency and effectiveness of vaccines. Adjuvants can be categorized into three groups based on their mechanisms: immune enhancers, delivery systems, and a combination of both. While aluminum salt-based adjuvants have been the long-standing choice for many commercial vaccines, the adjuvant landscape in FDA-approved vaccines has evolved. Emulsions, liposomes, virus-like particles (VLPs), and newer platforms have been integrated into specialized vaccine formulations. In the context of modern vaccine platforms, the need for optimized adjuvant-delivery systems is increasing. For messenger RNA (mRNA) vaccines, lipid nanoparticles (LNPs) serve as efficient delivery vehicles, enhancing mRNA stability and cellular uptake. Additionally, LNPs can also function as immune-activating adjuvants, which further enhance the immune response. Similarly, viral vector vaccines leverage adjuvants that improve immune activation, while DNA vaccines benefit from adjuvants that promote both antigen stability and uptake. Emerging systems, such as bacterial outer membrane vesicles (OMVs), programmable nanoparticles (responsive to pH, enzymes, or light), and cell membrane-coated systems (e.g., red blood cell or macrophage membranes), offer advanced ways to enhance vaccine delivery and immune responses. These systems also enable better targeting and control of immune activation, addressing challenges in immune memory and long-lasting vaccine efficacy. However, the development of adjuvant systems also faces safety concerns, including the potential for excessive immune activation and toxicity in certain populations. Overall, this review discusses the current and evolving landscape of adjuvant-delivery systems for vaccines, with an emphasis on systems that support diverse vaccine platforms and optimize immune balance, biocompatibility, and long-term immunity, crucial for the success of future vaccine development.
疫苗已成为预防和治疗疾病的一项重要战略。佐剂作为免疫增强剂和递送系统,在提高疫苗的效率和有效性方面起着至关重要的作用。佐剂可根据其机制分为三组:免疫增强剂、输送系统和两者的组合。虽然铝盐基佐剂一直是许多商业疫苗的长期选择,但fda批准的疫苗中的佐剂景观已经发生了变化。乳剂、脂质体、病毒样颗粒(vlp)和更新的平台已被整合到专门的疫苗配方中。在现代疫苗平台的背景下,对优化佐剂递送系统的需求正在增加。对于信使RNA (mRNA)疫苗,脂质纳米颗粒(LNPs)作为有效的递送载体,增强mRNA的稳定性和细胞摄取。此外,LNPs还可以作为免疫激活佐剂,进一步增强免疫应答。同样,病毒载体疫苗利用佐剂改善免疫激活,而DNA疫苗受益于佐剂促进抗原稳定性和摄取。新兴系统,如细菌外膜囊泡(omv)、可编程纳米颗粒(对pH值、酶或光有反应)和细胞膜包覆系统(如红细胞或巨噬细胞膜),为增强疫苗递送和免疫反应提供了先进的方法。这些系统还能够更好地靶向和控制免疫激活,解决免疫记忆和持久疫苗功效方面的挑战。然而,佐剂系统的发展也面临着安全问题,包括在某些人群中过度免疫激活和毒性的可能性。总之,本综述讨论了疫苗佐剂递送系统的现状和发展前景,重点是支持多种疫苗平台和优化免疫平衡、生物相容性和长期免疫的系统,这对未来疫苗开发的成功至关重要。
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引用次数: 0
Real-world data and clinical management experience in passive immunization for respiratory syncytial virus prevention in children 儿童呼吸道合胞病毒被动免疫预防的实际数据和临床管理经验
IF 2.2 Q3 IMMUNOLOGY Pub Date : 2025-09-25 DOI: 10.1016/j.jvacx.2025.100731
Yongping Xie, Xin Cong, Yan Li, Lisu Huang
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in children under 5 years of age worldwide. Currently, there are no approved curative treatments, and clinical management remains primarily focused on symptomatic support. As a result, preventive strategies are crucial for controlling RSV infections. Recent advancements have been made in the development of monoclonal antibody therapies aimed at protecting infants and young children from RSV. This review explores the application and real-world outcomes of passive immunization strategies in various international settings, particularly in developed countries, with a focus on their effectiveness and safety. The findings are intended to offer insights into the potential use of RSV passive immunization agents in developing countries.
呼吸道合胞病毒(RSV)是全世界5岁以下儿童急性下呼吸道感染的主要原因。目前,尚无批准的治愈性治疗方法,临床管理仍主要侧重于对症支持。因此,预防策略对于控制呼吸道合胞病毒感染至关重要。最近在开发旨在保护婴幼儿免受RSV感染的单克隆抗体疗法方面取得了进展。本综述探讨了被动免疫策略在各种国际环境中的应用和实际结果,特别是在发达国家,重点是其有效性和安全性。这些发现旨在为RSV被动免疫制剂在发展中国家的潜在使用提供见解。
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引用次数: 0
Effectiveness of vaccine dosing schedules for pneumococcal invasive disease in children: A systematic review and meta-analysis 儿童肺炎球菌侵袭性疾病疫苗剂量计划的有效性:一项系统综述和荟萃分析
IF 2.2 Q3 IMMUNOLOGY Pub Date : 2025-09-25 DOI: 10.1016/j.jvacx.2025.100734
Chia-Yuan Chang , Sharifa Nasreen , Manish Sadarangani , Kenny Aquino , Jacquelyn J. Cragg , Fawziah Marra

Objectives

Invasive pneumococcal disease (IPD) persists despite the effectiveness of 7-valent and 13-valent pneumococcal conjugate vaccines (PCV). As the protection offered by different dosing regimens remains uncertain, we evaluated the vaccine effectiveness (VE) against vaccine-type (VT) IPD in children based on the number of vaccine doses.

Methods

We searched MEDLINE/Embase/Web of Science/CENTRAL databases from January 2000 to December 2024 for studies on PCV7 and/or PCV13 VE against VT-IPD in children ≤18 years. VE estimates were recorded by vaccination status at IPD onset, classified into four groups (1) primary + booster group (1–3 primary doses <12 months of age plus 1 booster dose ≥12 months), (2) 1 primary dose group, (3) 2 primary doses group, and (4) 3 primary doses group (primary doses given <12 months of age and no booster).

Results

From 1982 studies, 25 studies were included, reporting 525 cases in the primary + booster group and 821 cases in the 1–3 primary dose(s) groups. Pooled VE from 14 studies was 94.4 % for the primary + booster group, and 66.8 %, 78.8 %, and 82.0 % for the 1-, 2-, and 3- primary dose(s) groups, respectively. Among VT-IPD breakthrough cases, serotype 19A was most common (27.9 %), followed by 19F (20.5 %) and 3 (18.9 %). Sensitivity analyses showed a VE of ∼95 % for the 2 + 1 and 3 + 1 schedules, versus 78.9 % for 3 + 0.

Conclusions

Our findings strongly support schedules that include a booster dose, such as the 2 + 1 regimen, as an optimal strategy for preventing VT-IPD in children.
目的:尽管7价和13价肺炎球菌结合疫苗(PCV)有效,但侵袭性肺炎球菌病(IPD)仍然存在。由于不同剂量方案提供的保护仍然不确定,我们根据疫苗剂量数评估了疫苗对儿童疫苗型IPD的有效性(VE)。方法检索MEDLINE/Embase/Web of Science/CENTRAL数据库,检索2000年1月至2024年12月PCV7和/或PCV13 VE在≤18岁儿童中抗VT-IPD的相关研究。根据IPD发病时的疫苗接种情况记录VE估计值,分为四组(1)初级+加强组(1 - 3次初级剂量+ 1次≥12个月的加强剂量),(2)1次初级剂量组,(3)2次初级剂量组,(4)3次初级剂量组(给予初级剂量+ 12个月的年龄,无加强剂量)。结果从1982年的研究中,纳入了25项研究,报告了525例原发性+加强剂组和821例1-3次原发性剂量组。从14项研究中汇总的VE,一次+加强剂组为94.4%,1、2、3次一次剂量组分别为66.8%、78.8%和82.0%。VT-IPD突破病例中以19A型最多见(27.9%),其次为19F型(20.5%)和3型(18.9%)。敏感性分析显示,2 + 1和3 + 1方案的VE为~ 95%,而3 + 0方案的VE为78.9%。结论:我们的研究结果强烈支持包括加强剂量的方案,如2 + 1方案,作为预防儿童VT-IPD的最佳策略。
{"title":"Effectiveness of vaccine dosing schedules for pneumococcal invasive disease in children: A systematic review and meta-analysis","authors":"Chia-Yuan Chang ,&nbsp;Sharifa Nasreen ,&nbsp;Manish Sadarangani ,&nbsp;Kenny Aquino ,&nbsp;Jacquelyn J. Cragg ,&nbsp;Fawziah Marra","doi":"10.1016/j.jvacx.2025.100734","DOIUrl":"10.1016/j.jvacx.2025.100734","url":null,"abstract":"<div><h3>Objectives</h3><div>Invasive pneumococcal disease (IPD) persists despite the effectiveness of 7-valent and 13-valent pneumococcal conjugate vaccines (PCV). As the protection offered by different dosing regimens remains uncertain, we evaluated the vaccine effectiveness (VE) against vaccine-type (VT) IPD in children based on the number of vaccine doses.</div></div><div><h3>Methods</h3><div>We searched MEDLINE/Embase/Web of Science/CENTRAL databases from January 2000 to December 2024 for studies on PCV7 and/or PCV13 VE against VT-IPD in children ≤18 years. VE estimates were recorded by vaccination status at IPD onset, classified into four groups (1) primary + booster group (1–3 primary doses &lt;12 months of age plus 1 booster dose ≥12 months), (2) 1 primary dose group, (3) 2 primary doses group, and (4) 3 primary doses group (primary doses given &lt;12 months of age and no booster).</div></div><div><h3>Results</h3><div>From 1982 studies, 25 studies were included, reporting 525 cases in the primary + booster group and 821 cases in the 1–3 primary dose(s) groups. Pooled VE from 14 studies was 94.4 % for the primary + booster group, and 66.8 %, 78.8 %, and 82.0 % for the 1-, 2-, and 3- primary dose(s) groups, respectively. Among VT-IPD breakthrough cases, serotype 19A was most common (27.9 %), followed by 19F (20.5 %) and 3 (18.9 %). Sensitivity analyses showed a VE of ∼95 % for the 2 + 1 and 3 + 1 schedules, versus 78.9 % for 3 + 0.</div></div><div><h3>Conclusions</h3><div>Our findings strongly support schedules that include a booster dose, such as the 2 + 1 regimen, as an optimal strategy for preventing VT-IPD in children.</div></div>","PeriodicalId":43021,"journal":{"name":"Vaccine: X","volume":"27 ","pages":"Article 100734"},"PeriodicalIF":2.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glutaraldehyde modifies the catalytic and binding subunits of pertussis toxin, affecting its toxicity and immunogenicity 戊二醛修饰百日咳毒素的催化和结合亚基,影响百日咳毒素的毒性和免疫原性
IF 2.2 Q3 IMMUNOLOGY Pub Date : 2025-09-19 DOI: 10.1016/j.jvacx.2025.100732
Wenming Wei , Chongyang Wu , Xi Wang , Xinyue Cui , Yuanzi Huo , Xinyu Li , Yuexia Liang , Bo Ma , Shuyuan Pan , Song Gao
Pertussis toxin (PTx) is a key virulence factor of the organism Bordetella pertussis, which must undergo proper detoxification as a component of acellular pertussis vaccines. Chemical detoxification using glutaraldehyde causes significant changes to the toxin surface, reducing its toxicity and potentially affecting its antigen properties. Although previous studies have thoroughly investigated the toxicity of chemically detoxified PT toxoid (PTd), there is limited understanding regarding how detoxification influences its antigenic properties and immunogenicity. Moreover, the specific parameters—such as glutaraldehyde concentration and buffer pH—and their effects on toxicity and immunogenicity are poorly defined. This study began by examining the influence of these parameters on the structural profiles of PTd. Subsequently, the toxicity and antigenic properties of PTd were characterized in vitro. Next, neutralizing epitopes remaining on PTd were quantified to assess the antigenicity. Finally, the immunogenicity of acellular pertussis vaccine candidates containing PTd was further evaluated in vivo. We found that the glutaraldehyde treatment caused more dramatic structural changes in B oligomer than A protomer of PTx, independent of variance in glutaraldehyde concentration and buffer pH. As a result, residual toxicity was reduced, and antigenic properties were altered. Following this, changes in antigenic properties were proved to be related to compromised immunogenicity. This study demonstrates that glutaraldehyde modulates the two functional domains of PTx, affecting both its toxicity and immunogenicity; two factors-glutaraldehyde concentration and buffer pH reduce the biochemical activities by bias influencing A protomer and B-oligomer. This work also underscores the importance of maintaining a delicate balance between immunogenicity and toxicity in detoxification.
百日咳毒素(PTx)是生物体百日咳博德泰拉的关键毒力因子,必须经过适当的解毒作为无细胞百日咳疫苗的组成部分。使用戊二醛进行化学解毒会使毒素表面发生显著变化,降低其毒性并可能影响其抗原特性。虽然以前的研究已经深入研究了化学解毒的PT类毒素(PTd)的毒性,但对解毒如何影响其抗原特性和免疫原性的了解有限。此外,戊二醛浓度和缓冲液ph等特定参数及其对毒性和免疫原性的影响尚不明确。本研究首先考察了这些参数对PTd结构剖面的影响。随后,对PTd的体外毒性和抗原性进行了表征。接下来,对PTd上剩余的中和表位进行量化以评估抗原性。最后,进一步在体内评价含PTd的无细胞百日咳候选疫苗的免疫原性。我们发现,与戊二醛浓度和缓冲液ph的变化无关,戊二醛处理导致PTx的B低聚物比A原聚物的结构变化更大,从而降低了残留毒性,改变了抗原性。在此之后,抗原特性的变化被证明与免疫原性受损有关。本研究表明戊二醛调节PTx的两个功能域,影响其毒性和免疫原性;戊二醛浓度和缓冲液pH通过偏置影响A原聚物和b低聚物来降低生物化学活性。这项工作还强调了在解毒过程中保持免疫原性和毒性之间微妙平衡的重要性。
{"title":"Glutaraldehyde modifies the catalytic and binding subunits of pertussis toxin, affecting its toxicity and immunogenicity","authors":"Wenming Wei ,&nbsp;Chongyang Wu ,&nbsp;Xi Wang ,&nbsp;Xinyue Cui ,&nbsp;Yuanzi Huo ,&nbsp;Xinyu Li ,&nbsp;Yuexia Liang ,&nbsp;Bo Ma ,&nbsp;Shuyuan Pan ,&nbsp;Song Gao","doi":"10.1016/j.jvacx.2025.100732","DOIUrl":"10.1016/j.jvacx.2025.100732","url":null,"abstract":"<div><div>Pertussis toxin (PTx) is a key virulence factor of the organism <em>Bordetella pertussis</em>, which must undergo proper detoxification as a component of acellular pertussis vaccines. Chemical detoxification using glutaraldehyde causes significant changes to the toxin surface, reducing its toxicity and potentially affecting its antigen properties. Although previous studies have thoroughly investigated the toxicity of chemically detoxified PT toxoid (PTd), there is limited understanding regarding how detoxification influences its antigenic properties and immunogenicity. Moreover, the specific parameters—such as glutaraldehyde concentration and buffer pH—and their effects on toxicity and immunogenicity are poorly defined. This study began by examining the influence of these parameters on the structural profiles of PTd. Subsequently, the toxicity and antigenic properties of PTd were characterized in vitro. Next, neutralizing epitopes remaining on PTd were quantified to assess the antigenicity. Finally, the immunogenicity of acellular pertussis vaccine candidates containing PTd was further evaluated in vivo. We found that the glutaraldehyde treatment caused more dramatic structural changes in B oligomer than A protomer of PTx, independent of variance in glutaraldehyde concentration and buffer pH. As a result, residual toxicity was reduced, and antigenic properties were altered. Following this, changes in antigenic properties were proved to be related to compromised immunogenicity. This study demonstrates that glutaraldehyde modulates the two functional domains of PTx, affecting both its toxicity and immunogenicity; two factors-glutaraldehyde concentration and buffer pH reduce the biochemical activities by bias influencing A protomer and B-oligomer. This work also underscores the importance of maintaining a delicate balance between immunogenicity and toxicity in detoxification.</div></div>","PeriodicalId":43021,"journal":{"name":"Vaccine: X","volume":"27 ","pages":"Article 100732"},"PeriodicalIF":2.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Vaccine: X
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