Human cytomegalovirus (HCMV) is widespread in the population, typically remaining latent. However, it can cause severe morbidity and mortality in transplant patients and immunodeficient individuals. Currently, there is no approved vaccine against HCMV. This study used immunoinformatics methods to predict the predominant T and B-cell epitopes of three key HCMV proteins, including phosphoprotein 65 (pp65), pp150, and immediate-early protein 1 (IE1). Subsequently, we synthesized a recombinant subunit vaccine (RHEc^{IE1/pp65/pp150}) from Escherichia coli, comprising RHEc-1 and RHEc-2. We observed that the RHEc^{IE1/pp65/pp150} vaccine exhibited high safety and immunogenicity in mice, enhancing a significant upregulation of CD80, CD86, CD40, and MHCII on dendritic cells and macrophages. Additionally, the vaccine activated innate immune responses through the NF-κB signalling pathway, triggering CD4⁺ and CD8⁺T cells to secrete tumour necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2, directing the T-cell response towards Th1. Moreover, it stimulated CD4⁺T cells to secrete IL-4, IL-6, and IL-10, promoting B-cell immunity. Furthermore, the RHEc^{IE1/pp65/pp150} vaccine induced the formation of abundant memory cells and high levels of neutralizing antibody titres, conducive to providing long-lasting protection. Taken together, the RHEc^{IE1/pp65/pp150} vaccine is a promising endeavour against HCMV, and these findings contribute valuable insights to the development of HCMV vaccine candidates.

2025-01-02·JOURNAL OF CLINICAL INVESTIGATION

A vaccine against cytomegalovirus: how close are we?

作者: Plotkin, Stanley A ; Permar, Sallie R ; Schleiss, Mark R

The pursuit of a vaccine against the human cytomegalovirus (HCMV) has been ongoing for more than 50 years. HCMV is the leading infectious cause of birth defects, including damage to the brain, and is a common cause of complications in organ transplantation. The complex biology of HCMV has made vaccine development difficult, but a recent meeting sponsored by the National Institute of Allergy and Infectious Diseases in September of 2023 brought together experts from academia, industry, and federal agencies to discuss progress in the field. The meeting reviewed the status of candidate HCMV vaccines under study and the challenges in clinical trial design in demonstrating efficacy against congenital CMV infection or the reduction of HCMV disease following solid organ transplantation or hematopoietic stem cell transplantation. Discussion in the meeting revealed that, with the numerous candidate vaccines that are under study, it is clear that a safe and effective HCMV vaccine is within reach. Meeting attendees achieved a consensus opinion that even a partially effective vaccine would have a major effect on the global health consequences of HCMV infection.

2024-10-01·VIROLOGIE

Challenges and advances in the management of HCMV infections

Review

作者: Hantz, Sébastien ; Gourin, Claire ; Alain, Sophie ; Mafi, Sarah ; Malnou, Cécile ; Flores, Thelma ; Ligat, Gaetan

Human cytomegalovirus (HCMV) is one of the most important causes of complications in immunocompromised patients and congenital infections. HCMV could also represent an interesting target for treatment to limit the progression of glioblastoma, a highly aggressive tumor. Ganciclovir, foscarnet and cidofovir, which interfere with the activity of the viral polymerase pUL54, are widely used in the treatment of transplant patients. However, their use in pregnant women remains limited or even contraindicated. On the other hand, hyperimmune immunoglobulins and valaciclovir have been shown to have a protective effect on the fetus. However, the toxicity of these treatments and the emergence of resistance mean that new therapeutic strategies need to be identified. Letermovir and maribavir have been developed to inhibit new targets, respectively the terminase complex and UL97 protein kinase. Their respective indications are the prevention of HCMV infection in haematopoietic stem cell transplant patients and the treatment of refractory HCMV infections. Finally, with the development of mRNA vaccines, the hope of one day seeing a prophylactic HCMV vaccine has never been greater. New therapeutic approaches are also being explored, but they still require extensive preclinical and clinical evaluation.

项与巨细胞病毒疫苗 (辉瑞) 相关的新闻（医药）

2024-05-23

·BioSpace

SpyBiotech Adds Epstein-Barr Virus Research and Development Collaboration with The University of Oxford

Agreement to support development of a vaccine against EBV OXFORD, England & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- SpyBiotech, a biotechnology company with novel vaccine platform technologies that can target infectious diseases, cancer, and chronic diseases, today announced a sponsored research agreement with The University of Oxford for the development of a vaccine against Epstein-Barr virus (EBV). EBV is a commonly spread virus that can lead to several serious health conditions including infectious mononucleosis and is linked to various cancers and multiple sclerosis. This research project will combine Oxford’s groundbreaking academic research capabilities with SpyBiotech’s proprietary SPYVLP platform technology in order to advance three vaccine candidates targeting EBV and test these in a Phase I clinical trial. “This research collaboration is an important step forward on a commonly spread virus with no currently available vaccines or therapeutics for its prevention or spread,” said Mark Leuchtenberger, Chief Executive Officer of SpyBiotech. “Studies have found that EBV triggers a range of very serious health conditions including certain cancers and multiple sclerosis. A recent study led by Stanford Medicine and senior author Dr. William Robinsoni notes that 99% of MS patients have EBV antibodies in their blood, indicating prior infection. We see a great need for a vaccine against EBV.” SpyBiotech’s novel SPYVLP vaccine platform is based on a proprietary protein “superglue” technology which binds antigens to vaccine delivery platforms in a way which minimizes delivery risk and enhances immunogenicity and efficacy. Under the terms of this agreement, SpyBiotech will provide Oxford researchers with access to the SPYVLP vaccine platform, and the Oxford team will work to advance the research into a Phase 1 clinical trial to be conducted through the University. “We are very keen to progress these vaccine candidates that target multiple EBV antigens to Phase I clinical trials with Professor Sandy Douglas and his team at the Jenner Institute, University of Oxford after seeing the promising pre-clinical data generated,” said Sumi Biswas, Ph.D., President and CSO of SpyBiotech. The company is currently conducting a Phase I trial assessing safety and immunogenicity of its HCMV vaccine. The study features a six-month dosing schedule and is being carried out in the UK. About Epstein-Barr virus (EBV) EBV is transmitted through saliva and is one of the most commonly spread human virusesii. Most people recover within a few weeks, but for some individuals EBV can lead to a number of health conditions including mononucleosis, meningitis, encephalitis and certain cancersiii. Recent research suggests people with multiple sclerosis and some lymphomas are more likely to have been infected with the virus. There are no currently available vaccines or therapeutics for the prevention or treatment of EBV. About SpyBiotech SpyBiotech is a clinical stage biotechnology company with novel vaccine platform technologies to target infectious diseases, cancer and chronic diseases. The company was spun out of the University of Oxford in 2017 by Oxford Science Enterprises (OSE) and Google Ventures (GV). The company raised $32.5 million in a Series A equity financing in 2021. Based on science developed at the University of Oxford, SpyBiotech’s novel vaccine platform is based on a proprietary protein “superglue” technology which binds antigens to vaccine delivery platforms in a way which minimizes delivery risk and enhances immunogenicity and efficacy. This makes it ideal for use against infectious diseases in challenging environments, such as in the developing world, but also with potential application in non-infectious disease settings such as cancer. SpyBiotech has the exclusive rights from the University of Oxford to apply, commercialize and sub-license the SpyTag/SpyCatcher and related “superglue” technologies in vaccine development. i Stanford Medicine. (2022, January 24). Study identifies how Epstein-Barr virus triggers multiple sclerosis. ii Centers for Disease Control and Prevention. (2020, September 28). About Epstein-Barr virus (EBV). Centers for Disease Control and Prevention. iii Centers for Disease Control and Prevention. (2020b, September 28). Epstein-Barr and mononucleosis: For Healthcare Providers. Centers for Disease Control and Prevention. View source version on businesswire.com: Contacts US Media: Karen Sharma ksharma@macdougall.bio +1 781-235-3060 UK Media: Sarah MacLeod, Adam Michael, Molly Ring Powerscourt Group spybiotech@powerscourt-group.com +44 (0)20 7250 1446 Source: SpyBiotech View this news release online at:

疫苗临床1期

2023-04-10

·佰傲谷BioValley

那些巨额投入新冠的药企还有出路吗？

自从新冠疫情爆发以来，医疗行业一直处于风口浪尖，药企也因此获得了更多机会。其中，以生产新冠疫苗、新冠特效药为主的药企收益最为明显。许多药企的股票价格和市值迎来大幅膨胀，例如，辉瑞、莫德纳等企业在2021年迎来了大幅上涨，市值也随之增长。不过随着入场者的逐渐增多，新冠疫情的逐渐消退。曾经那些斥巨资研发新冠药物，靠着新冠致富的的药企它们的未来会是怎样的？新冠腰斩的辉瑞在过去2022一整年中，辉瑞创造了1003亿美元营业收入。辉瑞旗下两款新冠产品尤其值得称道，贡献了超一半的营收，妥妥的“重磅炸弹”。可以说是新冠疫情彻底的将辉瑞推上了TOP1的宝座。但在今年情况将会不同，辉瑞的营收将面对断崖式的下降，辉瑞相关负责人在财报电话会议直言"新冠肺炎产品的收入将在2023年达到低点"。辉瑞预测，市场对其新冠药物Paxlovid和新冠疫苗需求将有所下降。辉瑞预测2023年新冠相关产品收入将有所下滑，其中Comirnaty收入预计为135亿美元，Paxlovid约80亿美元。这个数据与2022年的峰值形成了强烈反差，两款新冠产品大幅腰斩，Comirnaty的销售额将暴跌近2/3，Paxlovid的情况也并未好到哪里去，营收下降也远超一半。这意味着辉瑞将最起码减少1/4的营收。反观辉瑞的其他产品，年收入仅仅2%。辉瑞的前两位非新冠产品分别是抗凝药物Eliquis和肺炎疫苗Prevnar family。这两款产品的销售额加起来还不及新冠疫苗Comirnaty销售额的一半，可见其差距。而在肿瘤领域，辉瑞一直不温不火。乳腺癌的Ibrance是辉瑞手中唯一一款50亿级别的肿瘤药，其次是Inlyta（阿昔替尼）和Xtandi（恩扎卢胺）两款10亿美元级别的药。以上几款非新冠关键药物的专利也即将到期。预计辉瑞在两年后的收入损失将高达180亿美元，加上新冠产品的逐渐式微，辉瑞急需新的重磅药物来填补即将到来的窟窿。积极求变的Moderna如果说Moderna的发家史源自于自身的 mRNA 技术，那Moderna的致富之路离不开新冠。自从Moderna的新冠疫苗Spikevax在2020年首次获得FDA紧急使用授权之后，在2021-2022年内凭借这一款产品，狂揽378亿美元入账，市值曾一度飙到千亿美元。不过在去年，Moderna的新冠疫苗便开始出现下滑的迹象。2022年Moderna的季度总收入至少同比下跌20%以上，Q3、Q4两季度总收入分别同比下跌32.3%和30%。根据Moderna在2月公布的2022年业绩报告中，Spikevax在2023年的营收估计仅仅50亿美元左右，相较于去年可能仅仅只有1/4的销售额。除此之外，在最新的财报中，这家巨头还提到正面临的来自新冠产能过剩和产品库存积压的问题。对于账上有着182亿美元的现金的Moderna而言，现在主动求变是来得及的。2023年，Moderna预计增加研发投入45亿美元，计划将35个非新冠开发药物进入临床试验阶段，包括mRNA流感疫苗、RSV疫苗、巨细胞病毒（CMV）疫苗、癌症疫苗等等。甚至在基因治疗，Moderna也先后与和铂医药、Life Edit Therapeutics达成协议，以发现和开发基因免疫疗法、体内mRNA基因编辑疗法。国产新冠药...近日，腾盛博药发布公告，决定结束安巴韦单抗/罗米司韦单抗联合疗法项目，并已停止生产工作以将资源重新转向核心项目，停产是因为不断演变的疫情趋势。这也是首个停产的国产新冠药。安巴韦单抗/罗米司韦单抗是腾盛博药与清华大学、深圳市第三人民医院合作研发的新冠病毒中和抗体联合治疗药物，也是国内首款获批的新冠新药，从获批到商业化经历了8个月，从商业化到停产也只经历了8个月。安巴韦单抗/罗米司韦单抗研发投入达2亿美元（约合人民币13.78亿元），研发利用率不到4%。上市半年多时间，仅为腾盛博药带来5160万元收入。该药在2022年7月在国内开始商业化，向全国25个省份358家医院提供了该疗法。可以说安巴韦单抗/罗米司韦单抗在商业化覆盖面以及国内新冠高峰的时间点都没大问题，却仍然停产草草收尾。有人指出，安巴韦单抗/罗米司韦单抗的问题是因为药物本身为中和抗体的特点，费用较高，且碰到Omicron越来越快的变异，导致重症人数比例大幅下降，影响了安巴韦单抗/罗米司韦单抗的商业化推进。可这一因素面对今年年初获批的国产新冠小分子药同样适用。氢溴酸氘瑞米德韦片（商品名：民得维）为795元/疗程；先声药业的先诺特韦/利托那韦组合包装（商品名称：先诺欣）为750元/疗程；真实生物的阿兹夫定片平均445元/疗程（医保前540元，医保后350元）。这些小分子药对于轻症患者而言仍然太贵，远不如身体硬抗加布洛芬和对乙酰氨基酚来的划算。药物选择方面，除了国产小分子药外，还有着辉瑞的Paxlovid，1890元/疗程；默沙东的莫诺拉韦，1500元/疗程参与竞争。在国内市场，新冠特效药的选择太多，而新冠疫情又越来越弱，越来越少。这些国产新冠小分子药都投入了超过5亿元的研发费用，但能否获得相应的营收前景令人担忧。相较于辉瑞、Moderna而言，国内药企的现金流是远远不够他们像国际大药企一样疯狂烧钱拓展新管线。在新冠药皆不断腰斩的未来中，那些投入巨资研发新冠的国内药企恐怕未来日子会不好过。参考资料：1.https://mp.weixin.qq.com/s?__biz=MjM5NTI3MDE0NQ==&mid=2653710375&idx=5&sn=61571335137d75f6e00a4ef5ad54178d&chksm=bd23d3498a545a5fc2c8796462703512c32fe735764a4f00e65e36176b7f77e2cbf3453f0950&scene=272.https://mp.weixin.qq.com/s/EMJm0ZP6zzzFcLQEWR51fQ近期热门视频更多精彩视频，尽在佰傲谷视频号，欢迎关注~本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀点亮在看，传递信息♥

财报疫苗信使RNA紧急使用授权

2023-03-09

·Pharmaceutical Technology

SpyBiotech reveals plans for UK-based HCMV vaccine trial in H2 2023

Image Credit: Shutterstock / Numstocker Oxford, UK-based vaccine company SpyBiotech is planning to start dosing subjects for a Phase I trial of its lead vaccine candidate against human cytomegalovirus (HCMV) infection in H2 2023, says chief scientific officer (CSO) Sumi Biswas. The preparations for the trial are moving ahead and manufacturing is already completed, says Biswas. Additionally, the company has already selected a CRO for this trial, with toxicity studies well underway, confirms CEO Mark Leuchtenberger. The study, which features a six-month dosing schedule, will be carried out in the UK, he adds. The Phase I trial will test three doses of the vaccine, says Biswas. While the trial size has not been finalised, the biotech expects to enroll 120 subjects, she adds. Sumi Biswas, CSO of SpyBiotech, Image Credit; SpyBiotech The trial will feature the company’s vaccine candidate that is based on its “protein superglue” approach, which can be used to efficiently attach different antigens to virus-like particle (VLP)-based vaccines. Designing new vaccines for different pathogens becomes much faster once this “superglue” is incorporated into a specific platform, explains Biswas. Leuchtenberger likens SpyBiotech’s approach to a car chassis. This chassis can be modified based on needs, which is more efficient than building a car up from scratch every time. SpyBiotech aims to have immunogenicity and safety data ready by the end of 2023 or the start of 2024, says Leuchtenberger. While this data will not be shared with the public at the time, it will help the company with deciding the next steps for plans related to financing and partnerships, he adds. Mark Leuchtenberger, CEO of SpyBiotech Image Credit: SpyBiotech Plans for funding and other candidates in the works Though the company remains in a financially stable position in a challenging environment, it may start considering potential partnerships and a Series B fundraise in Q1 2024, says Leuchtenberger. The company previously raised $32.5 million in a Series A round, based on a February 2021 press release. This round extended the company’s reserves until H2 2025, adds Leuchtenberger. In addition to its plans for an HCMV vaccine, the company is exploring vaccines in other indications, including cancer. SpyBiotech recently decided to go ahead with the development of a vaccine candidate for Epstein-Barr virus, says Leuchtenberger. There are no approved vaccines for this condition . Additionally, the company’s technology will be featured in an Oxford University-sponsored malaria vaccine trial, says Leuchtenberger. Further in the works, negotiation is currently underway for the development of a mosaic-8 Covid-19 vaccine, which features the company’s technology, the CEO says. While Biswas did not give concrete timelines for when these enter the clinic, she hopes it will be soon. Note: Paragraph 2 was updated to reflect new context provided on the Phase I plans after publication.