排名前五的靶点	数量

HLA-DRB1(major histocompatibility complex, class II, DR beta 1)	3
EphA2(A型肝配蛋白受体-2)	2
SARS-CoV-2 S protein(新冠病毒刺突蛋白)	2
TLR9(Toll样受体9)	2
NF-κB(核因子NF-κB复合体)	2

关联

项与 Osaka University 相关的药物

Varicella attenuated live vaccine(Osaka University)

水痘减毒活疫苗(Osaka University)

靶点-

作用机制

免疫刺激剂

在研机构

Osaka University [+1]

原研机构

Osaka University

在研适应症

水痘

非在研适应症

麻疹 [+3]

最高研发阶段批准上市

首次获批国家/地区

澳大利亚

首次获批日期2015-04-16

Freeze-dried, Cell Culture-derived Japanese Encephalitis Vaccine

干燥细胞培养日本脑炎疫苗(Osaka University)

靶点-

作用机制

免疫刺激剂

在研机构

Osaka University

原研机构

Osaka University

在研适应症

日本脑炎

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期2009-02-23

Cupabimod

靶点

NF-κB

作用机制

NF-κB抑制剂

在研机构

Nippon Zoki Pharmaceutical Co. Ltd. [+3]

原研机构

AnGes, Inc.

在研适应症

特应性皮炎

非在研适应症

椎间盘退化 [+1]

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期-

326

项与 Osaka University 相关的临床试验

NCT06924151

/ Not yet recruitingN/AIIT

the Prospective, Randomized, Controlled, Multi-center Study to Establish the Safety and Effectiveness of Isolated Surgical Aortic Valve Replacement in Low Risk Patients Who Have Symptomatic Severe Aortic Stenosis

To establish the safety and effectiveness of surgical aortic valve replacement (SAVR) in patients with isolated severe, calcific aortic stenosis who are at low surgical risk.

开始日期2025-06-01

申办/合作机构

Osaka University

NCT06826027

/ Active, not recruitingN/AIIT

TAV-in-SAV in Japanese Patients

Background In 2018, transcatheter aortic valve in surgical aortic valve (TAV-in-SAV) in high risk patients was approved for the treatment of bioprosthetic valve dysfunction due to aging, for which valve replacement had been selected. It has been reported that early and mid-term results of TAV-in-SAV differ depending on the sizes of the original surgical bioprosthetic valves. Especially, the prognoses of TAV-in-SAV in patients with surgical bioprosthetic valves of ≤21 mm in size are reported to be poor in the United States and Europe. Bioprosthetic valves of ≥21 mm in size are thus tended to be used also in Japan after the annular was enlarged in the initial surgery as needed. The patient group in the above-mentioned report, however, consisted of larger patients (with the mean body surface area of 1.85 m2). It has therefore been unknown whether the above report applies to smaller patients in Japan. Furthermore, in terms of the surgical results for valvular disease, not only short-term results, but also repeat surgery avoidance rate, as well as medium- and long-term results, including the occurrence rate of complications related to artificial valves, are important factors, but the characteristic of this disease, the number of cases at each facility is not that large, so there have been no comprehensive reports of TAV-in-SAV in Japan. Accordingly, the investigators will investigate TAV-in-SAV performed at Osaka University as well as multiple centers in Japan to: understand the facts; assess the appropriateness of the evaluation of the above-mentioned paper; and examine early and mid-term treatment results of TAV-in-SAV in patients with narrow bioprosthetic valves, which are specific to Japanese patients. The investigators also plan to study early and mid-term treatment results of TAV-in-SAV using a self-expanding valve because self-expanding valves generally produce favorable hemodynamics in narrow bioprosthetic valves.
Study Objectives i. To study early and mid-term results of transcatheter aortic valve implantation in patients with aortic bioprosthetic valve dysfunction (hereinafter referred to as TAV-in-SAV).
ii. To compare clinical results, including hemodynamics, of TAV-in-SAV between small aortic bioprosthetic valves (19 or 21 mm in size) and aortic bioprosthetic valves of other sizes.
iii. To compare clinical results, including hemodynamics, of TAV-in-SAV between a self-expanding valve and a balloon-expandable valve.
Study Methods i. Study design A multicenter, retrospective, observational study using existing data. ii. Endpoints
Study endpoints are as follows:
Primary endpoint: Death during the observation period The mortality among all patients registered in this study will be estimated with the Kaplan-Meier method.
Secondary endpoints: Analyses of major cardiac and cerebral events (MACCE) and factors associated with death. The rate of freedom from MACCE among all patients registered in this study will be estimated with the Kaplan-Meier method. Factors associated with death will be explored using a Cox proportional hazards model.
Hemodynamics and events including death and MACCE will also be compared between aortic bioprosthetic valves of 19 or 21 mm in size and those of other sizes.
In addition, hemodynamics and events including death and MACCE will be compared between a self-expanding valve (Evolut) and a balloon-expandable valve (SAPIEN) using propensity-matching analyses.

开始日期2024-08-07

申办/合作机构

Osaka University

JPRN-UMIN000054046

/ SuspendedN/AIIT

Investigation of changes in taste receptor genes and oral microbiota induced by dashi addition - Investigation of changes in taste receptor genes and oral microbiota induced by dashi addition

开始日期2024-06-01

申办/合作机构

Osaka University

100 项与 Osaka University 相关的临床结果

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0 项与 Osaka University 相关的专利（医药）

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183,645

项与 Osaka University 相关的文献（医药）

2025-12-31·Journal of Oral Microbiology

Effect of Helicobacter pylori on enamel and dentin development – an in vitro study in mice

Article

作者: Sahlberg, Carin ; Rice, David P. ; Nomura, Ryota ; Alaluusua, Satu ; Salmela, Eija ; Nakano, Kazuhiko

Objective:

A heavy infection in a primary molar tooth can impair the enamel formation of the underlying permanent successor. Helicobacter pylori colonizes primarily the stomach, but it has also been detected in oral samples, including in the dental pulp of infected primary teeth. Here, we aim to test if H. pylori can disturb enamel and dentin formation.

Methods:

Mandibular molar explants of E18.5 mice were grown for 12 days in media containing 10% of H. pylori cell lysates. The presence and extent of enamel and dentin on the mesial surface of the first molar explants were evaluated from stereomicroscopic photographs and histologically.

Results:

The statistical analyses revealed that less enamel was formed in the test (N = 47) than in the control first molars (N = 28, p < 0.001). Most severe disturbances were seen in explants grown in media containing H. pylori cell lysates, which were made from stationary growth-phase cultures, with high optical density. Histological findings showed that dentin mineralization was also impaired.

Conclusion:

The results suggest that H. pylori disturbs enamel and dentin development in cultured mouse embryonic molar teeth. This provides new insight into the etiology of enamel disturbances in permanent teeth.

2025-12-31·SCIENCE AND TECHNOLOGY OF ADVANCED MATERIALS

Next-generation hydrogen peroxide sensors based on ordered carbonaceous frameworks derived from iron porphyrin

Article

作者: Yoshii, Takeharu ; Itoh, Tetsuji ; Shimizu, Shunsuke ; Kamiya, Kazuhide ; Nakatsuji, Hirotaka ; Hasegawa, Yasuhisa ; Nishihara, Hirotomo ; Yoshida, Akiko ; Chida, Koki

Carbon materials with ordered frameworks and atomically dispersed metal sites, referred to as ordered carbonaceous frameworks (OCFs), have attracted considerable attention for their promising potential in fundamental research and diverse practical applications, particularly in electrocatalysis. In this work, we synthesize Fe-incorporated OCF (Fe-OCF) with a heme-like structure through structure-preserving pyrolysis of Fe-porphyrin with four ethynyl groups. Fe-OCF is characterized by its ordered microporous framework, incorporating atomically dispersed Fe(III) sites with a high content of 6.9 wt%, analogous to metal-organic frameworks. At the same time, Fe-OCF possesses the advantages of carbon materials, including chemical stability, thermal stability, and electrical conductivity. Remarkably, Fe-OCF mimics the functionality of a sensor enzyme by facilitating the redox reaction of hydrogen peroxide, which is regulated by an applied potential, thereby enabling bidirectional catalytic behavior. Fe-OCF exhibits a linear reduction current response to hydrogen peroxide, underscoring its efficient electron transfer and catalytic properties. Moreover, Fe-OCF demonstrates superior stability compared to molecular Fe-porphyrin, further emphasizing its potential application as a novel hydrogen peroxide sensor. These results emphasize the significant potential of Fe-based OCFs as advanced materials for artificial enzyme applications and next-generation hydrogen peroxide sensing technology.

2025-12-31·SCIENCE AND TECHNOLOGY OF ADVANCED MATERIALS

Advances in bioinspired polymer hydrogel systems with biomedical functionalities

Review

作者: Ishihara, Kazuhiko

The concepts of bioinspiration and biomimetics that seek to elucidate the morphology and functions of living organisms and specific reactions within cells, and extraction of important elements from these concepts to design functional molecules and high-performance materials are becoming more and more widespread. This review summarizes the progress in research on hydrogels inspired by the stimuli-responsiveness of cell functions. For application to a self-regulated release system of insulin to regulate blood glucose levels, various polymer hydrogels have been designed using bioactive molecules such as enzymes and lectins to sense glucose concentrations. In addition, as a fully synthetic glucose-responsive hydrogel, a complex of a polymer having phenylboronic acid groups that form reversible bonds with sugars and a multivalent hydroxyl group polymer has been researched. This reversible hydrogel system can be further developed to act as an extracellular matrix in which cells can preferably reside. The proliferation and differentiation of encapsulated cells in hydrogels are controlled by reversible changes in the hydrogel properties in response to sugar. Another advantage is that cells can be safely retrieved by adding sugar to dissociate the hydrogel. These bioinspired polymer hydrogels can serve as important materials for the development of new medical technologies, such as the controlled release of bioactive molecules, regulated cell culture environmental matrices, and applications in layered and three-dimensional cell culture systems to create organized tissue structures.

196

项与 Osaka University 相关的新闻（医药）

2025-06-18

·PRNewswire

NIPTE Celebrates 20 Years of Advancing US Pharmaceutical Development and Manufacturing, Initiates New Industry Collaboration and Workforce Development Efforts

NIPTE continues its long-held mission to promote quality and availability of medicines in the US. MINNEAPOLIS, June 18, 2025 /PRNewswire/ -- The National Institute for Pharmaceutical Technology and Education (NIPTE) is a multi-university organization that facilitates pre-competitive collaboration between academia, industry, and government to address challenges that face the US pharmaceutical supply chain. The non-profit group, which is celebrating its 20-year anniversary, has supported modernization of pharmaceutical development and manufacturing. Research performed at NIPTE's member universities was key to advancing new concepts that are now widely used tools. Students trained in these programs are now serving in various capacities in FDA, academia, and industry. Today, NIPTE focuses on alleviating drug shortages and improving accessibility of essential medicines through research and training in advanced pharmaceutical manufacturing methods. These technologies, such as continuous manufacturing and artificial-intelligence-enabled manufacturing, are seen as critical for bringing manufacturing of pharmaceutical ingredients and finished drug products back to the US. Another need is development of a skilled US talent pipeline, from operators through advanced-degree scientists. Through the new NIPTE Industrial Consortium for Workforce Development, NIPTE faculty offer continuing education training programs that can be customized for specific industry requirements. NIPTE's latest initiative is the Advisory Council on Industry Relations. The Advisory Council will connect corporate sponsors with academic researchers, fostering new collaborations and increasing interactions between the pharmaceutical industry and faculty members and scientists across all NIPTE institutions. "The Council will facilitate NIPTE's efforts to advance pharmaceutical innovation, modernize domestic manufacturing, and strengthen the workforce to ensure a resilient, secure and future-ready supply chain for modern medicines," says Dr. James Drennen, Dean of the School of Pharmacy and Graduate School of Pharmaceutical Sciences at Duquesne University and current Chair of NIPTE's Board of Directors. "NIPTE represents more than 100 faculty members with a wide range of expertise. We are seeking industrial partners interested in joining this collaborative industry-academia partnership," says Dr. Vadim J. Gurvich, Executive Director of NIPTE and Research Associate Professor at the University of Minnesota. About NIPTE The National Institute for Pharmaceutical Technology and Education (NIPTE) is a non-profit academic organization of 17 US universities that collaborate with industry, academia, and government to improve the way medicines are designed, developed, and manufactured to meet the needs of patients. SOURCE National Institute for Pharmaceutical Technology and Education (NIPTE) WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

2025-06-15

·ioncology

ASCO 巅峰对话丨殷咏梅教授、王坤教授深度对话，ASCENT-04开启TNBC一线治疗新篇章

编者按：三阴性乳腺癌（TNBC）是当前预后最差的乳腺癌亚型之一。随着近年来诊疗技术的发展，免疫治疗、抗体偶联药物（ADC）为TNBC带来了新的选择，其中靶向Trop-2 的ADC戈沙妥珠单抗（SG）已成为TNBC二线治疗的标准方案[1]。2025年美国临床肿瘤学会（ASCO）年会上，戈沙妥珠单抗联合帕博利珠单抗一线治疗PD-L1阳性TNBC的III期ASCENT-04/KEYNOTE-D19研究作为LBA，重磅披露了阳性结果，显示较标准的化疗联合免疫方案降低了35%的疾病进展或死亡风险，安全可控，奠定了ADC+免疫治疗一线应用于TNBC的基础[2]。因此，《肿瘤瞭望》于ASCO会议现场邀请江苏省人民医院殷咏梅教授与广东省人民医院王坤教授展开对话，分享对ASCENT-04研究结果的评价，展望未来TNBC一线治疗格局的发展前景。01肿瘤瞭望：此次ASCO大会公布了ASCENT-04研究的初步结果，显示了Trop-2 ADC戈沙妥珠单抗联合帕博利珠单抗一线治疗晚期TNBC的优势。首先，请您分享一下该研究的设计及主要结果。殷咏梅教授江苏省人民医院ASCENT-04研究[2]是一项全球性、多中心、开放标签、随机Ⅲ期临床研究，主要针对既往未经晚期系统治疗、无法手术的PD-L1阳性（CPS≥10）局部晚期或转移性三阴性乳腺癌（TNBC）患者，评估戈沙妥珠单抗联合帕博利珠单抗vs化疗联合帕博利珠单抗一线应用的疗效和安全性。该研究的主要终点是经盲法独立中央审查（BICR）使用RECIST v1.1确定的无进展生存期（PFS）。次要终点包括总生存期（OS）、客观缓解率（ORR）、缓解持续时间（DOR）、缓解开始时间（TTR）、患者报告结局（PROs）和安全性（图1）。图1. 研究设计该研究共纳入了443名PD-L1阳性TNBC患者，按1:1随机分组后予以戈沙妥珠单抗联合帕博利珠单抗和化疗联合帕博利珠单抗方案。该研究达到了PFS的主要研究终点，与化疗联合帕博利珠单抗相比，戈沙妥珠单抗联合帕博利珠单抗降低了疾病进展或死亡风险达35%，具有统计学显著性和临床意义（11.2个月 vs 7.8个月; HR 0.65, 95%CI 0.51-0.84; P = 0.0009）（图2上）。OS尚不成熟，但也展现了早期获益的趋势。戈沙妥珠单抗联合帕博利珠单抗方案具有更高的ORR（60% vs 53%），并显示出深度且持久的缓解（完全缓解：13% vs 8%；DOR 16.5个月 vs 9.2个月）（图2，下）。安全性方面，与既往戈沙妥珠单抗及帕博利珠单抗研究一致，未见新的不良事件信号。患者耐受性较好，戈沙妥珠单抗联合帕博利珠单抗组与化疗联合帕博利珠单抗组的不良事件相关停药率为12% vs 31%，为更多患者可以完整接受治疗带来了保障。图2. ASCENT-04研究BICR评估的PFS（上）、缓解状况（下）该研究是首次证实了ADC联合免疫治疗方案可一线应用于TNBC的Ⅲ期临床研究，为TNBC一线治疗带来了新的选择。02肿瘤瞭望：ASCENT-04研究是首次确立ADC联合免疫治疗一线应用地位的Ⅲ期研究。您如何评价该研究结果？将为晚期TNBC治疗格局带来怎样的变化？王坤教授广东省人民医院随着近年来免疫治疗的发展，国内外指南愈加强调免疫治疗联合化疗在TNBC应用的重要性，特别是对于PD-L1阳性患者，免疫治疗联合化疗已成为标准治疗方案[3,4]。此次ASCENT-04研究数据的披露，证实了对于PD-L1阳性（CPS≥10）的患者，一线戈沙妥珠单抗联合免疫治疗优于化疗联合免疫治疗。该结果既确证了Trop-2 ADC联合免疫治疗一线应用的可行性，又标志着Trop-2 ADC从此正式从TNBC二线及其后线治疗迈入一线。在免疫联合化疗作为目前TNBC一线标准治疗方案的背景下，ASCENT-04研究的阳性结果必将改写指南，改变临床实践。随着ASCENT-04研究的成功，我也期待在中国人群中开展相应的桥接研究或类似的临床研究，来验证戈沙妥珠单抗联合免疫治疗的疗效。目前江泽飞教授牵头的多中心、随机、对照的ASCENT-C04研究（图3）正在进行中，旨在探索戈沙妥珠单抗联合特瑞普利单抗对比特瑞普利单抗联合化疗一线治疗TNBC的表现，期待其结果能早日披露，为临床提供更多可能。图3. ASCENT-C04研究设计此外，近日ASCENT-03研究（NCT 05382299）披露信息显示已达到主要终点，取得了高度显著且具有临床意义的PFS改善[5]。该研究旨在验证戈沙妥珠单抗对比化疗在不适合接受PD-1/PD-L1单抗治疗的TNBC患者一线治疗的地位。戈沙妥珠单抗在TNBC一线治疗的全面突破，必将改变一线治疗的临床格局，期待戈沙妥珠单抗能够早日获批该适应症，为患者带来更多的临床治疗选择。03肿瘤瞭望：在ASCENT-04研究的基础上，您对戈沙妥珠单抗联合免疫治疗应用于中国临床实践有哪些期待？殷咏梅教授江苏省人民医院ASCENT-04研究在全球人群中确立了戈沙妥珠单抗联合帕博利珠单抗一线治疗PD-L1阳性乳腺癌的地位。该研究主要针对PD-L1阳性的TNBC患者，我相信对于该人群而言，ASCENT-04研究提供的戈沙妥珠单抗联合帕博利珠单抗方案将替代当前的化疗联合免疫治疗方案。我非常期待未来Trop-2 ADC联合免疫治疗不仅能够为患者带来ORR改善，还能为患者带来更好的总体生存获益。04肿瘤瞭望：在临床实践中，安全性管理直接影响患者生活质量及生存时间。ADC联合免疫治疗存在哪些常见的不良事件？应如何管理？王坤教授广东省人民医院ASCENT-04研究中，戈沙妥珠单抗联合帕博利珠单抗最常见不良事件为中性粒细胞减少和腹泻，未见其他新的安全信号，与既往文献报告一致，也未见间质性肺病（ILD）、眼毒性、口腔炎等不良事件，临床应用安全可控（图4）。图4. ASCENT-04研究的常见不良事件对于中性粒细胞减少，可使用粒细胞刺激因子（G-CSF）等二级预防；对于存在中性粒细胞减少高风险患者，可以使用G-CSF一级预防；若出现了严重的中性粒细胞减少伴发热，则须开始抗感染治疗。对于腹泻，可通过及时监测并对症补液、补充电解质、使用洛哌丁胺等止泻治疗有效控制[6]。此外，还需要通过患教活动等提高患者对不良事件的认知，做到早发现、早处理。参考文献：（滑动查看）[1] Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021;384(16):1529-1541. doi:10.1056/NEJMoa2028485[2] Sara M. Tolaney, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. 2025 ASCO LBA 109.[3] 中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会（CSCO）乳腺癌诊疗指南2025. 人民卫生出版社-北京. 2025.04.[4] ESMO Living Guideline Metastatic Breast Cancer 2025v1.2. Available at：https://www.esmo.org/guidelines/living-guidelines/esmo-living-guideline-metastatic-breast-cancer/triple-negative-breast-cancer/de-novo-mbc-or-recurrence-6-12-months-after-the-end-of-neo-adjuvant-ici[5] Gilead Sciences, Inc. ASCENT-03: Trodelvy® Demonstrates Highly Statistically Significant & Clinically Meaningful Improvement in Progression Free Survival in Patients With First-line Metastatic Triple-Negative Breast Cancer Who Are Not Candidates for Checkpoint Inhibitors. Available at：https://www.gilead.com/news/news-details/2025/ascent-03-trodelvy-demonstrates-highly-statistically-significant--clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-first-line-metastatic-triple-negative-breast[6] 中国医师协会肿瘤医师分会乳腺癌学组,中国抗癌协会国际医疗交流分会. 中国乳腺癌抗体药物偶联物安全性管理专家共识[J]. 中华肿瘤杂志,2022,44(09)：913-927.殷咏梅教授教授，主任医师，博士生导师江苏省人民医院（南京医科大学第一附属医院、江苏省妇幼保健院）副院长中国临床肿瘤学会(CSCO)副理事长北京市希思科临床肿瘤学研究基金会副理事长第19届St.Gallen国际乳腺癌大会专家团成员CSCO乳腺癌专家委员会秘书长中国抗癌协会乳腺癌专业委员会常委CSCO患者教育专家委员会主任委员CSCO BC指南执笔专家荣获2021年度，2023年度中国生物医药产业链创新风云榜“Leading Pl桂冠奖”王坤教授广东省人民医院肿瘤医院副院长博士研究生导师CSCO和CBCS乳腺癌专委会常委2019年国之名医获得者2021年NeoCART研究入选美国NCCN乳腺癌指南2023年人民好医生-乳腺癌领域杰出贡献奖获得者（来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

ASCO会议临床结果抗体药物偶联物临床3期

2025-06-10

·生物制药小编

申报临床！高血压疫苗发展史

随着生物制药行业的逐步发展，癌症疫苗已经不是新鲜的概念，不过你有听过高血压疫苗吗？近日，根据CDE官网公布的6月7日消息，武汉华纪元生物已经向NMPA提交了HJY-ATRQβ-001注射液的新药临床申请。根据公开渠道消息可知，HJY-ATRQβ-001注射液是一款用于预防高血压的疫苗，本文将就高血压疫苗管线的发展历史进行简单介绍。肾素疫苗在上世纪有人尝试使用肾素作为高血压疫苗，肾素是由肾脏球旁细胞产生和分泌的一种蛋白水解酶，能够催化血管紧张素原（AGT）转化为血管紧张素I（Ang I）。血管紧张素I在血管紧张素转换酶（ACE）的作用下进一步转化为血管紧张素II（Ang II）。而血管紧张素II是强效的血管收缩剂，可导致血压升高，同时促进醛固酮分泌，增加水钠潴留，进一步升高血压。（这也是为什么血管紧张素Ⅱ受体阻滞剂在心血管领域中得到大规模应用）理论上，抑制其活性可从源头阻断高血压的关键病理通路。然而，实践中却发现，通过注射外源性肾素来诱导肾素抗体针对人体肾素的操作很容易会让人体换上自免疾病。患者的血压确实有降低，但是因此患上了自免肾病。因此安全性问题让人们对于肾素疫苗开发望而却步。Ang I疫苗后来的尝试则试图通过肾素以外的通路入手，如英国Protherics公司试图开发一款针对Ang I的疫苗PMD-3117，旨在通过诱导机体产生针对Ang I的抗体，阻断肾素-血管紧张素系统（RAAS）的激活，从而降低血压。然而，实际临床中发现降压效果并不明显。原因可能包括抗体滴度不足以显著降低血压，以及Ang I抗体主要存在于血浆中，无法有效阻止组织中的Ang I转化为Ang II。为了提高疫苗效果，研究人员尝试将PMD-3117的佐剂调整为“CoVaccine HTTM”（水包油佐剂），该佐剂能刺激疫苗中的抗原成分产生更强的B细胞免疫反应，提高抗原相关免疫球蛋白G抗体的形成。然而，自从2008年出现了相关严重剂量相关性不良反应，II期临床最终于2010年终止。同济大学附属医学院的Fang Hong等人将内源性 AngⅠ与牛血清白蛋白共价结合，以氢氧化铝作为佐剂，研制出血管紧张素肽（angiotensin peptides, Ang I-R）。在小鼠模型中成功降低了血压，不过未见后续临床。Ang II疫苗瑞士Cytos公司研制的针对血管紧张素II的CYT006-AngQb疫苗曾经被认为是极有希望的降压疫苗。其具体机制在于疫苗本身含有与Ang II结构相似的抗原表位。当疫苗被注射到体内后，抗原呈递细胞（如树突状细胞）会摄取并处理这些抗原，将其呈递给T细胞和B细胞。B细胞在抗原刺激和T细胞辅助下，会分化为浆细胞并产生特异性抗体。这些抗体能够识别并结合Ang II，从而中和其活性。在后续临床试验中，与安慰剂组相比，该疫苗的高剂量组将受试者的日间平均动态血压从基线水平下调-9/-4mm Hg，可惜的是，这一降压幅度还不能完全满足临床实际要求。而且该疫苗的降压效果可能因个体差异而异，部分患者可能对疫苗无应答。这可能和疫苗产生的抗体亲和力太低有关系，抑或是针对血管紧张素II疫苗免疫会诱导肾素-血管紧张素系统反馈激活有关，这可能在一定程度上削弱了疫苗的降压效应。另外，大阪大学的Nakagami团队及大阪大学发起的风投制药公司AnGes共同开发了多款Ang II疫苗，每一款都在原有基础上进行改进和迭代，根据公司官网消息和公开渠道，该Ang II疫苗似乎几年前就在澳大利亚完成了II期临床，但是未见下文。Ang II1R疫苗Ang II通过两种受体亚型发挥作用：AT1R和AT2R。AT1R介导了Ang II的绝大多数病理生理效应，包括血管收缩、血压升高、心肌肥厚、纤维化及炎症反应等。相比之下，AT2R的作用尚不完全明确，但可能与血管扩张、抗增殖及组织修复相关。靶向AT1R被认为是规避肾素-血管紧张素系统（RAS）的反馈激活机制的一种方法。2006年武汉华纪元生物的创始人廖玉华及其团队开发一款AngⅡ受体疫苗ATR-12181。它由鼠源性AT1R的抗原短肽、TT和弗氏佐剂组成。后续在2013年廖玉华团队开发了ATRQβ-001，这是一款从人AT1R的胞外第二环中选取线性表位ATR-001与Qβ噬菌体VLP 结合制成 ATRQβ-001疫苗。ATRQβ-001疫苗具有更长的抗体半衰期（14.4天）在ATRQβ-001疫苗组中，也未观察到循环或局部肾素-血管紧张素系统（RAS）的明显反馈激活。同年华纪元生物成立。2017年，廖玉华团队还开发人血管平滑肌细胞L型钙通道和血管紧张素1型受体的嵌合型二价降压疫苗，这是在现有疫苗开发针对单一靶点的情况下进行的优化设计。团队找到一段来源于L型CaV1.2钙通道的线性表位，它能诱导针对L型钙通道的特异性抗体，并且降低高血压动物模型的血压，因此可以作为另一个新的治疗性高血压疫苗靶点。东京大学的Tatsuhiko Azegami团队开发了一款血管紧张素II型受体-肺炎球菌表面蛋白A (AT1R-PspA)疫苗。该AT1R部分肽与PspA和环二胍盐一磷酸佐剂缀合，可通过鼻内给予自发性高血压大鼠(SHR)。用AT1R-PspA疫苗进行鼻内免疫具有同时减弱高血压发展和保护免于致死性肺炎球菌感染的潜力。参考来源：[1]刘书情,周妍.抗高血压疫苗的研究进展[J].心脑血管病防治,2022,22(05):75-78+87.相关专利

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