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Reduced risk of CIN2+ recurrence in women immunized with a 9-valent HPV vaccine post-excision: Retrospective cohort study. 切割术后接种 9 价 HPV 疫苗的女性 CIN2+ 复发风险降低:回顾性队列研究。
IF 4.8 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-05-09 DOI: 10.1080/21645515.2024.2343552
Vladimír Dvořák, Marek Petráš, Vladimír Dvořák, Danuše Lomozová, Pavel Dlouhý, Ivana Králová Lesná, Radovan Pilka

The main aim of our study was to investigate the specific contribution of a 9-valent human papillomavirus vaccine (9vHPV) to the recurrence risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women vaccinated post-excision. Therefore, we conducted a retrospective monocentric cohort study in women aged 22-49 years undergoing conization between 2014 and 2023. The 9vHPV-vaccinated women were matched to unvaccinated women for age and follow-up duration in a 1:2 ratio to eliminate allocation bias. The risk of CIN2+ recurrence was estimated by the incidence rate ratio using Poisson regression with adjustment for comorbidities, smoking status, nulliparity, CIN grade, positive cone margin, and HPV genotypes. The CIN2+ recurrence rates in 147 women enrolled in the analysis were 18 and 2 cases per 100,000 person-days for unvaccinated and vaccinated women, respectively, during a mean follow-up period of 30 months (±22 months). A reduction in CIN2+ recurrences by 90% (95% confidence interval: 12-99%) was documented in 9vHPV-vaccinated participants compared to women undergoing only surgical excision. Moreover, vaccinated women with a positive cone margin showed a 42% (though non-significant) reduction in relapse (p = .661). Full post-conization vaccination with the 9vHPV contributed to an additional reduction in the risk of CIN2+ recurrence. This finding is consistent with current knowledge and suggests a high adjuvant effect of the 9vHPV vaccine.

我们研究的主要目的是调查九价人乳头瘤病毒疫苗(9vHPV)对宫颈切除术后接种疫苗的女性宫颈上皮内瘤变 2 级或更坏(CIN2+)复发风险的具体影响。因此,我们对 2014 年至 2023 年期间接受锥切术的 22-49 岁女性进行了一项回顾性单中心队列研究。为消除分配偏倚,接种过 9vHPV 疫苗的女性与未接种过疫苗的女性在年龄和随访时间上按 1:2 的比例进行了配对。CIN2+复发的风险是通过泊松回归的发病率比值估算的,并对合并症、吸烟状况、未产妇、CIN等级、锥体边缘阳性和HPV基因型进行了调整。在平均 30 个月(±22 个月)的随访期间,未接种疫苗和接种疫苗的 147 名妇女的 CIN2+ 复发率分别为每 10 万人天 18 例和 2 例。与只接受手术切除的妇女相比,接种9vHPV疫苗的妇女CIN2+复发率降低了90%(95%置信区间:12-99%)。此外,接种过疫苗且锥缘呈阳性的女性复发率降低了 42%(尽管并不显著)(p = .661)。锥切后全程接种 9vHPV 可进一步降低 CIN2+ 复发的风险。这一发现与目前的知识相符,表明 9vHPV 疫苗具有很高的佐剂效应。
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引用次数: 0
Association between combination COVID-19-influenza vaccination and long COVID in middle-aged and older Europeans: A cross-sectional study. 欧洲中老年人接种 COVID-19 流感混合疫苗与长效 COVID 之间的关系:一项横断面研究。
IF 4.8 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-05-09 DOI: 10.1080/21645515.2024.2345505
Wenyan Wu, Xiaowei Zheng, Huan Ding, Tongtong Miao, Yuhan Zang, Suwen Shen, Yumeng Gao

The potential impact of combined COVID-19 and influenza vaccination on long COVID remains uncertain. In the present cross-sectional study, we aimed to investigate the plausible association between them in middle-aged and older Europeans based on the Survey of Health, Ageing, and Retirement in Europe (SHARE). A total of 1910 participants were recruited in the analyses. The study outcome was long COVID. Participants were divided into 4 groups through the self-reported status of COVID-19 and influenza vaccination. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. 1397 participants experienced long COVID. After multivariable adjustment, those vaccinated with neither COVID-19 nor influenza vaccine had higher risk of long COVID (OR, 1.72; 95% CI, 1.26-2.35) compared to those vaccinated with both vaccines. Furthermore, adding the 4 statuses of COVID-19 vaccination/influenza vaccination to conventional risk model improved risk reclassification for long COVID (continuous net reclassification improvement was 16.26% [p = .003], and integrated discrimination improvement was 0.51% [p = .005]). No heterogeneity was found in the subgroup analyses (all p-interaction ≥0.05). Our study might provide a strategy for people aged 50 and over to reduce the occurrence of long COVID, that is, to combine the use of the COVID-19 vaccine and influenza vaccines.

合并接种 COVID-19 和流感疫苗对长期 COVID 的潜在影响仍不确定。在本横断面研究中,我们以欧洲健康、老龄和退休调查(SHARE)为基础,旨在调查欧洲中老年人中这两者之间可能存在的关联。分析共招募了 1910 名参与者。研究结果为长 COVID。根据自我报告的 COVID-19 和流感疫苗接种情况,参与者被分为 4 组。研究估算了比值比 (OR) 和 95% 置信区间 (CI)。1397名参与者经历了长COVID。经多变量调整后,与同时接种两种疫苗的人相比,既未接种COVID-19疫苗也未接种流感疫苗的人发生长COVID的风险更高(OR,1.72;95% CI,1.26-2.35)。此外,在传统风险模型中加入 COVID-19 疫苗接种/流感疫苗接种的 4 种状态可改善长 COVID 的风险再分类(连续净再分类改善率为 16.26% [p=0.003],综合判别改善率为 0.51% [p=0.005])。亚组分析中未发现异质性(所有 p-交互作用均≥0.05)。我们的研究可能为 50 岁及以上人群提供了一种减少长 COVID 发生的策略,即联合使用 COVID-19 疫苗和流感疫苗。
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引用次数: 0
COVID-19 vaccines: Immune correlates and clinical outcomes. COVID-19 疫苗:免疫相关性和临床结果
IF 4.8 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-03-22 DOI: 10.1080/21645515.2024.2324549
Shant H Mahrokhian, Lisa H Tostanoski, Samuel J Vidal, Dan H Barouch

Severe disease due to COVID-19 has declined dramatically as a result of widespread vaccination and natural immunity in the population. With the emergence of SARS-CoV-2 variants that largely escape vaccine-elicited neutralizing antibody responses, the efficacy of the original vaccines has waned and has required vaccine updating and boosting. Nevertheless, hospitalizations and deaths due to COVID-19 have remained low. In this review, we summarize current knowledge of immune responses that contribute to population immunity and the mechanisms how vaccines attenuate COVID-19 disease severity.

由于疫苗的广泛接种和人口的自然免疫,COVID-19 导致的严重疾病已大幅减少。随着 SARS-CoV-2 变种的出现,这些变种在很大程度上可以逃避疫苗诱导的中和抗体反应,原有疫苗的效力已经减弱,需要进行疫苗更新和强化。尽管如此,COVID-19 导致的住院和死亡人数仍然很低。在这篇综述中,我们总结了目前有关免疫反应的知识,这些免疫反应有助于提高人群免疫力,以及疫苗如何减轻 COVID-19 疾病严重程度的机制。
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引用次数: 0
Reply to "Knowledge-map analysis and bladder cancer immunotherapy: Comment". 回复 "知识图谱分析与膀胱癌免疫疗法:评论"。
IF 4.8 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-03-27 DOI: 10.1080/21645515.2024.2325756
Zongwei Lv, Junhui Hou, Yuan Wang, Xia Wang, Yibing Wang, Kefeng Wang
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引用次数: 0
Healthcare workers' willingness to receive COVID-19 booster dose and associated factors in the Democratic Republic of the Congo. 刚果民主共和国医护人员接受 COVID-19 强化剂量的意愿及相关因素。
IF 4.8 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-05-23 DOI: 10.1080/21645515.2024.2357214
Bertin Mindje Kolomba, Francois Kalenga Luhembwe, Deca Blood Banza Ndala, Pacifique Kanku Wa Ilunga, Paul Ciamala Mukendi, Amide Ngongo Kitenge, John Ngoy Lumbule, Elie Kilolo Ngoy, Antoine Umba Ilunga, Judith Mbidi Miema, Christelle Kalikat Mwavita, Guillaume Ngoy Mwamba, Aime Cikomola Wa Bene, Audry Mulumba Wakamba, Alain Ngashi Ngongo, Michel Kabamba Nzaji

The COVID-19 booster dose is considered an important adjunct for the control of the COVID-19 pandemic due to reports of reduced immunity in fully vaccinated individuals. The aims of this study were to assess healthcare workers' intention to receive the booster dose of COVID-19 vaccine and to identify predictive factors among healthcare workers. A cross-sectional study was conducted among healthcare workers selected in two provinces, Kasai Oriental, and Haut-Lomami. Data were collected using a questionnaire administered through structured face-to-face interviews, with respondents using a pre-tested questionnaire set up on the Open Data Kit (ODK Collect). All data were analyzed using SPSS v26.0 (IBM Corporation, Armonk, NY, USA). Vaccination coverage for COVID-19, considering declarations by health workers, is around 85.9% for the province of Kasai Oriental and 85.8% for Haut-Lomami. A total of 975 responses were collected, 71.4% of health workers at Kasai Oriental and 66.4% from Haut-Lomami declared a definite willingness to receive a COVID-19 vaccine booster. The duration of protection was the main reason for accepting a booster COVID-19 dose for 64.6% of the respondents. Logistic regression analysis showed that having chronic diseases (aOR = 2.95 [1.65-5.28]), having already received one of the COVID-19 vaccines (aOR = 2.72 [1.43-5. 19]); the belief that only high-risk individuals, such as healthcare professionals and elderly people suffering from other illnesses, needed a booster dose (aOR = 1.75 [1.10-2.81]). Considering the burden of COVID-19, a high acceptance rate for booster doses could be essential to control the pandemic. Our results are novel and could help policymakers design and implement specific COVID-19 vaccination programs to reduce reluctance to seek booster vaccination.

由于有报道称完全接种过疫苗的人免疫力下降,COVID-19加强剂被认为是控制COVID-19大流行的重要辅助手段。本研究旨在评估医护人员接种 COVID-19 加强剂疫苗的意愿,并确定医护人员的预测因素。研究在东开赛省和上洛马米省两个省份的医护人员中进行了横断面研究。通过结构化面对面访谈的方式进行问卷调查,受访者使用在开放数据工具包(ODK Collect)上设置的预检问卷收集数据。所有数据均使用 SPSS v26.0(IBM 公司,美国纽约阿蒙克)进行分析。根据卫生工作者的申报,COVID-19 疫苗接种覆盖率在东开赛省约为 85.9%,在上洛马米省约为 85.8%。共收集到 975 份答复,71.4% 的东开赛省卫生工作者和 66.4% 的上洛马米省卫生工作者明确表示愿意接种 COVID-19 强化疫苗。64.6%的受访者接受 COVID-19 强化接种的主要原因是保护期。逻辑回归分析表明,患有慢性疾病(aOR = 2.95 [1.65-5.28])、已经接种过一种 COVID-19 疫苗(aOR = 2.72 [1.43-5.19])、认为只有高危人群(如医护人员和患有其他疾病的老人)才需要接种加强剂(aOR = 1.75 [1.10-2.81])。考虑到 COVID-19 带来的负担,较高的加强剂量接受率对于控制大流行至关重要。我们的研究结果很新颖,可以帮助政策制定者设计和实施特定的COVID-19疫苗接种计划,以减少不愿意接种强化疫苗的情况。
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引用次数: 0
An optimized caries model of Streptococcus mutans in rats and its application for evaluating prophylactic vaccines. 优化的大鼠变异链球菌龋齿模型及其在评估预防性疫苗中的应用。
IF 4.8 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-05-17 DOI: 10.1080/21645515.2024.2345943
Bowen Liu, Min Li, Xian Li, Jingyi Yang, Huimin Yan

Dental caries is a prevalent oral disease that mainly results from Streptococcus mutans. Susceptibility to S. mutans decreased rapidly after weaning in a well-known rat model. However, owing to the lack of time to establish protective immunity ahead of challenge, the weaning rat model is suboptimal for assessing prophylactic vaccines against S. mutans infection. In this study, we found that, in adult rats, S. mutans cultured under air-restricted conditions showed dramatically increased colonization efficacy and accelerated development of dental caries compared with those cultured under air-unrestricted conditions. We propose that S. mutans cultured under air-restricted conditions can be used to develop an optimal caries model, especially for the evaluation of prophylactic efficacy against S. mutans. Therefore, we used the anti-caries vaccine, KFD2-rPAc, to reevaluate the protection against the challenge of S. mutans. In immunized rats, rPAc-specific protective antibodies were robustly elicited by KFD2-rPAc before the challenge. In addition to inhibiting the initial and long-term colonization of S. mutans in vivo, KFD2-rPAc immunization showed an 83% inhibitory efficacy against the development of caries, similar to that previously evaluated in a weaning rat model. These results demonstrate that culturing under air-restricted conditions can promote S. mutans infection in adult rats, thereby helping establish a rat infection model to evaluate the prophylactic efficacy of vaccines and anti-caries drugs.

龋齿是一种常见的口腔疾病,主要由变异链球菌引起。在一种著名的大鼠模型中,对变异链球菌的易感性在断奶后迅速下降。然而,由于断奶后的大鼠缺乏时间来建立保护性免疫,因此断奶后的大鼠模型并不适合用来评估预防性疫苗对变异链球菌感染的效果。在这项研究中,我们发现,与在空气不受限制的条件下培养的大鼠相比,在空气受限制的条件下培养的成年大鼠中,变异杆菌的定植效果显著提高,龋齿的发展速度加快。我们建议,在空气限制条件下培养的变异杆菌可用于开发最佳龋齿模型,尤其是用于评估对变异杆菌的预防效果。因此,我们使用抗龋疫苗 KFD2-rPAc 来重新评估对变异杆菌挑战的保护作用。在免疫大鼠中,KFD2-rPAc能在挑战前激发出强效的rPAc特异性保护抗体。KFD2-rPAc 免疫除了能抑制变异杆菌在体内的初始和长期定植外,对龋齿发展的抑制效果也达到了 83%,与之前在断奶大鼠模型中评估的效果相似。这些结果表明,在空气受限的条件下培养可促进成年大鼠感染变异杆菌,从而有助于建立大鼠感染模型,以评估疫苗和抗龋药物的预防效果。
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引用次数: 0
Parental knowledge on the respiratory syncytial virus before the nirsevimab immunization program: Attitudes toward immunization in an autonomous community of Spain. 尼舍韦单抗免疫计划实施前家长对呼吸道合胞病毒的了解:西班牙一个自治区对免疫接种的态度。
IF 4.8 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-06-10 DOI: 10.1080/21645515.2024.2357439
Matilde Zornoza Moreno, Jaime Jesús Pérez Martín, Mª Cruz Gómez Moreno, Mª Pilar Ros Abellán

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children and associated with most bronchiolitis- and pneumonia-related hospitalizations. A new preventive monoclonal antibody (MAb), nirsevimab, has been launched in the United States, Luxembourg, and France, and was recently approved to be given in a population-based manner throughout Spain. This study aimed to have a first pre-immunization insight into the Spanish parental knowledge about bronchiolitis, RSV, and nirsevimab immunization. Parents in Murcia with children <2 years of age up to the date of September 1, 2023, were selected to complete a questionnaire. The primary endpoint was the parental knowledge about bronchiolitis, RSV, and nirsevimab. A total of 3,217 responses were analyzed. The majority (95.8%) were aware of bronchiolitis. Meanwhile, 46.6% of the respondents knew about RSV, most of them only after the first child's birth. Information about RSV or bronchiolitis was mainly obtained from family members, with only 4.8% reporting having been informed by Health care Professionals (HCPs). Only 11.2% of respondents were aware of nirsevimab. Nonetheless, these were not entirely satisfied with the information received (score of 3.3 out of 5) and shared that HCPs should be the primary source of information. The present survey then highlights the need for better and more efficient educational strategies directed to all parents/legal guardians. It also sheds some light on the different factors that should be considered to improve awareness of RSV immunization to decrease its burden in Spain and beyond.

呼吸道合胞病毒(RSV)是幼儿下呼吸道感染的主要病因,也与大多数支气管炎和肺炎相关的住院治疗有关。一种新的预防性单克隆抗体(MAb)--nirsevimab 已在美国、卢森堡和法国上市,最近又获准在西班牙全国范围内以人群为基础使用。这项研究的目的是在免疫前首次了解西班牙家长对支气管炎、RSV 和 nirsevimab 免疫的认识。穆尔西亚有孩子的家长
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引用次数: 0
Bridging the gap: The future of biosimilars regulations. 缩小差距:生物仿制药法规的未来。
IF 4.1 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-12-31 Epub Date: 2024-06-17 DOI: 10.1080/21645515.2024.2362450
Anan S Jarab, Shrouq R Abu Heshmeh, Ahmad Z Al Meslamani

Biosimilar vaccines and immunotherapeutic are innovative approaches in medical research. This commentary addresses the current disparities in regulations of biosimilar vaccines and immunotherapeutic products across different nations. It also navigates the benefits of global regulatory alignment and challenges that may be encountered. The current discrepancies in regulations across different countries, which pose significant challenges for the development and approval of biosimilar vaccines and immunotherapeutic products. These disparities often lead to delayed market access, increased development costs, and hindered innovation. The commentary stresses that such obstacles could be mitigated through harmonized regulations, resulting in faster approvals, reduced healthcare costs, and improved patient outcomes. Moreover, the commentary explores the specific complexities associated with biosimilar vaccines and immunotherapeutic, such as the intricate evaluation of biosimilarity due to their molecular composition and immunogenic properties. In conclusion, the editorial advocates for collaborative efforts to overcome the challenges in achieving global regulatory harmonization for biosimilars. This includes establishing uniform standards, fostering international cooperation among regulatory agencies, and promoting educational initiatives for healthcare providers and regulators. The ultimate goal is to ensure that patients worldwide have timely access to safe, effective, and affordable biosimilar treatments.

生物仿制疫苗和免疫疗法是医学研究的创新方法。本评论探讨了目前不同国家对生物仿制疫苗和免疫治疗产品监管的差异。它还介绍了全球统一监管的好处和可能遇到的挑战。目前不同国家的法规存在差异,这给生物仿制疫苗和免疫治疗产品的开发和审批带来了巨大挑战。这些差异往往导致市场准入延迟、开发成本增加和创新受阻。评注强调,这些障碍可以通过统一法规来缓解,从而加快审批速度、降低医疗成本并改善患者疗效。此外,评论还探讨了与生物仿制疫苗和免疫疗法相关的特殊复杂性,例如由于其分子组成和免疫原性,对生物仿制性的评估错综复杂。最后,社论倡导各方共同努力,克服在实现生物仿制药全球统一监管方面的挑战。这包括建立统一标准、促进监管机构之间的国际合作以及推动针对医疗服务提供者和监管机构的教育活动。最终目标是确保全球患者能够及时获得安全、有效和负担得起的生物仿制药治疗。
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引用次数: 0
Risk and safety profile in checkpoint inhibitors on non-small-cel lung cancer: A systematic review. 检查点抑制剂治疗非小细胞肺癌的风险和安全性概况:系统综述。
IF 4.1 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-31 Epub Date: 2024-06-27 DOI: 10.1080/21645515.2024.2365771
Sara Maria Majernikova

Treating non-small-cell lung cancer (NSCLC) has gained increased importance in recent years due to the high mortality rate and dismal five-year survival rate. Immune checkpoint inhibitors (ICI) are a promising approach with exceptional outcomes in NSCLC thanks to the antigenic nature of cells. Conversely, immune system over-stimulation with ICI is a double-edged sword that can lead to various negative effects ranging from mild to life-threatening. This review explores current breakthroughs in nanoparticle-based ICI and their limitations. The PubMed, Scopus and Web of Science were examined for relevant publications. Thirty-eight trials (N = 16,781) were included in the analyses. The mixed effects analyses on quantifying the treatment effect contributed significantly to the subgroups within studies for ICI treatment effect. Models confirmed ICI's higher impact on treatment effectivity and the decrease in respondents' mortality compared to conventional treatment regiments. ICI might be used as first-line therapy due to their proven effectiveness and safety profile.

近年来,由于非小细胞肺癌(NSCLC)的高死亡率和令人沮丧的五年生存率,其治疗变得越来越重要。免疫检查点抑制剂(ICI)是一种很有前景的方法,由于细胞的抗原性,它在治疗非小细胞肺癌方面效果显著。相反,免疫系统过度刺激 ICI 是一把双刃剑,可导致轻微到危及生命的各种负面影响。本综述探讨了目前基于纳米粒子的 ICI 取得的突破及其局限性。我们在 PubMed、Scopus 和 Web of Science 上查阅了相关出版物。38项试验(N = 16,781)被纳入分析。量化治疗效果的混合效应分析极大地促进了ICI治疗效果研究中的分组。模型证实,与传统治疗方案相比,ICI 对治疗效果的影响更大,受访者的死亡率也更低。由于 ICI 的有效性和安全性已得到证实,因此可将其用作一线疗法。
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引用次数: 0
Exosome may be the next generation of promising cell-free vaccines. 外泌体可能是下一代前景广阔的无细胞疫苗。
IF 4.1 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-31 Epub Date: 2024-05-07 DOI: 10.1080/21645515.2024.2345940
Zelan Dai, Ruiru Cai, Hong Zeng, Hailian Zhu, Youwei Dou, Shibo Sun

Traditional vaccines have limits against some persistent infections and pathogens. The development of novel vaccine technologies is particularly critical for the future. Exosomes play an important role in physiological and pathological processes. Exosomes present many advantages, such as inherent capacity being biocompatible, non-toxic, which make them a more desirable candidate for vaccines. However, research on exosomes are in their infancy and the barriers of low yield, low purity, and weak targeting of exosomes limit their applications in vaccines. Accordingly, further exploration is necessary to improve these problems and subsequently facilitate the functional studies of exosomes. In this study, we reviewed the origin, classification, functions, modifications, separation and purification, and characterization methods of exosomes. Meanwhile, we focused on the role and mechanism of exosomes for cancer and COVID-19 vaccines.

传统疫苗在预防某些顽固性感染和病原体方面存在局限性。开发新型疫苗技术对未来尤为重要。外泌体在生理和病理过程中发挥着重要作用。外泌体具有许多优点,如与生俱来的生物相容性和无毒性,使其成为更理想的疫苗候选物质。然而,对外泌体的研究还处于起步阶段,外泌体产量低、纯度低、靶向性弱等障碍限制了其在疫苗中的应用。因此,有必要进一步探索如何改善这些问题,进而促进外泌体的功能研究。本研究综述了外泌体的起源、分类、功能、修饰、分离纯化和表征方法。同时,我们重点研究了外泌体在癌症和COVID-19疫苗中的作用和机制。
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引用次数: 0
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Human Vaccines & Immunotherapeutics
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