Monkeypox

Clinical study in children 2-11 years of age follows the recent EMA and WHO approvals of the MVA-BN mpox vaccine for adolescents 12-17 of age. COPENHAGEN, Denmark, October 29, 2024 – Bavarian Nordic A/S (OMX: BAVA) announced today the initiation of a clinical study of the MVA-BN® mpox/smallpox vaccine in children 2 to 11 years of age. The first children have now been vaccinated in the study, which is currently enrolling in the Democratic Republic of Congo (DRC) with plans also to include sites in Uganda. A total of 460 individuals are expected to participate in the study, which will compare the safety and immunogenicity of the vaccine between children aged 2 to 11 years of age to adults. The study (NCT06549530) is partially funded by the Coalition for Epidemic Preparedness Innovations (CEPI). Results from this study could support an extension of the current approval of MVA-BN to include children from 2 years of age and older. Last month, the WHO prequalified the vaccine for adolescents 12 to 17 years of age, adopting the recent approval from the European Medicines Agency (EMA) for this age group. Paul Chaplin, President & CEO of Bavarian Nordic, said: “Children remain highly vulnerable to mpox infections in the ongoing outbreak in Africa, highlighting the importance and urgency to broaden the access to effective vaccines that can be safely administered to this young population. Following the recent approval of MVA-BN for adolescents, we are pleased to initiate this study, which could provide additional data to further extend the indication to also include children, and we thank CEPI and our partners in Africa for their support of this important work.” Dr Nicole Lurie, Executive Director of Preparedness and Response at CEPI, said: “The findings of this study will be crucial in shaping mpox vaccine strategies that could protect children and bring an end to this devastating and widespread outbreak, while also providing pivotal vaccine guidance in local endemic populations to tackle mpox outbreaks that could strike in the future.” While this study represents the first investigation of MVA-BN as an mpox/smallpox vaccine for younger children, a recombinant version of MVA-BN (Mvabea®) was approved by EMA in 2020 as part of a prime-boost vaccine regimen1 for the prevention of disease caused by Ebola virus in individuals 1 year of age and older. Clinical studies supporting this approval encompassed more than 3,300 individuals across Europe, USA, and Africa including over 800 children and adolescents 1 to 17 years of age in Africa2. The safety profile of Mvabea in children 1 to 17 years of age was generally similar to that observed in adults. About the mpox vaccineMVA-BN or Modified Vaccinia Ankara-Bavarian Nordic is the only non-replicating mpox vaccine approved in the U.S., Switzerland, Singapore and Mexico (marketed as JYNNEOS®), Canada (marketed as IMVAMUNE®), and the EU/EAA and United Kingdom (marketed as IMVANEX®). Originally developed as a smallpox vaccine in collaboration with the U.S. government to ensure the supply of a smallpox vaccine for the entire population, including immunocompromised individuals who are not recommended vaccination with traditional replicating smallpox vaccines, MVA-BN has been indicated for use in the general population (from 12 years old) in individuals considered at risk for smallpox or mpox infection. About Bavarian NordicBavarian Nordic is a global vaccine company with a mission to improve health and save lives through innovative vaccines. We are a preferred supplier of mpox and smallpox vaccines to governments to enhance public health preparedness and have a leading portfolio of travel vaccines. For more information, visit www.bavarian-nordic.com. Forward-looking statements This announcement includes forward-looking statements that involve risks, uncertainties and other factors, many of which are outside of our control, that could cause actual results to differ materially from the results discussed in the forward-looking statements. Forward-looking statements include statements concerning our plans, objectives, goals, future events, performance and/or other information that is not historical information. All such forward-looking statements are expressly qualified by these cautionary statements and any other cautionary statements which may accompany the forward-looking statements. We undertake no obligation to publicly update or revise forward-looking statements to reflect subsequent events or circumstances after the date made, except as required by law. ContactsEurope: Rolf Sass Sørensen, Vice President Investor Relations, rss@bavarian-nordic.com, Tel: +45 61 77 47 43US: Graham Morrell, Paddock Circle Advisors, graham@paddockcircle.com, Tel: +1 781 686 9600 1 Mvabea® was licensed in 2014 to Johnson & Johnson as part of a prime-boost vaccine regimen. 2 https://www.ema.europa.eu/en/documents/assessment-report/mvabea-epar-public-assessment-report_en.pdf Attachment 2024-10-29-en

mRNA疫苗技术的兴起 疫苗是医学上最重要的进步之一，在预防传染病和改善全球健康方面发挥着至关重要的作用。天花疫苗的成功是医疗史上的一项巨大成就，它导致了一种曾经毁灭性的疾病的完全根除，并展示了疫苗方法的有效性。从创建第一个天花疫苗到沿途获得的洞察，为疫苗技术的当代进步铺平了道路，包括mRNA疫苗的出现。 mRNA疫苗技术是一项近期的革命性进步，为抗击病毒提供了快速开发和灵活部署的能力。这种创新方法，指导细胞产生抗原蛋白，以其在COVID-19大流行期间前所未有的成功而声名鹊起，展示了快速发展、适应性和高效性，从而标志着抗击传染病的新时代。这些现代疫苗与其传统的对应物形成鲜明对比，后者使用弱化或灭活的病毒形式来刺激免疫，而是采用开创性的方法，利用遗传蓝图来触发免疫防御（图1A）。这一演变突出了疫苗发展的连续性，从早期的接种技术到今天复杂的遗传方法，这些方法正在重新定义我们对免疫的方法。 mRNA疫苗在全球COVID-19大流行紧急情况下的应用 mRNA疫苗技术的引入为疫苗开发开辟了新的视野。COVID-19大流行加速了mRNA疫苗的开发和部署。前所未有的全球健康危机需要迅速响应，而mRNA技术的灵活性允许快速设计和测试针对新型冠状病毒的疫苗。辉瑞-BioNTech（BNT162b2）和Moderna（mRNA-1273）疫苗成为首批获得针对SARS-CoV-2的紧急使用授权（EUA）的mRNA疫苗，同时还有CureVac、赛诺菲/TranslateBio、Arcturus/新加坡杜克-国大医学院、伦敦帝国理工学院、Providence Therapeutics、Abogen Biosciences、CSPC Pharmaceutical等许多其他参与者也参与了这一追求。 辉瑞-BioNTech（BNT162b2）和Moderna（mRNA-1273）疫苗针对病毒的刺突蛋白，两者都包含编码该蛋白的mRNA序列，这些序列都经过了修改。它们包括在986和987位置的两个脯氨酸替代，被称为“2P”突变，这锁定了刺突蛋白在其融合前构象。位于刺突蛋白S1和S2亚基交界处的弗林切割位点被移除，以防止过早切割并确保刺突蛋白保持在其融合前状态。 编码抗原的mRNA被封装在脂质纳米颗粒中以实现有效递送。虽然它们的临床试验展示了显著的效力，但部署工作面临了一些挑战，例如mRNA疫苗的热稳定性，这一问题最近已基本解决。mRNA疫苗显示出高效性、安全性和适应性，为未来针对各种传染病的疫苗开发铺平了道路。Moderna能够迅速更新其疫苗的mRNA序列以应对刺突蛋白突变，例如在SARS-CoV-2的Beta、Delta和Omicron变体中发现的突变，这展示了mRNA技术在应对全球紧急情况下新变种的有效潜力。 mRNA疫苗在应对全球猴痘爆发中的作用 猴痘的再次出现和全球传播已升级为公共卫生危机，迫切需要快速开发既有效又安全的疫苗。猴痘病毒（MPV），一种人畜共患病原体，自2022年1月以来导致感染激增，全球110个国家确认了超过80,000例病例。2022年7月，世界卫生组织（WHO）宣布猴痘为全球卫生紧急情况。这一警报级别曾与COVID-19、脊髓灰质炎、埃博拉和寨卡病毒爆发等重大全球危机相关联，代表了WHO发出的最严重分类。该病毒被归类为两个分支：中非和西非，后者病情较轻，但负责当前的全球爆发。在其复制过程中，MPV产生两种不同的病毒颗粒：包膜病毒（EV）和成熟病毒（MV）。EV在感染的初期阶段通过外泌作用从感染的宿主细胞中释放，而MV在后期通过宿主细胞溶解释放。尽管两者都能感染新的宿主，但EV和MV在表面蛋白的组成上表现出对比，每种在免疫原性和感染性方面都有独特的特性。 为了应对猴痘爆发，多个研究小组迅速使用mRNA疫苗技术开发了针对MPV的疫苗候选物。从MPV表面蛋白的一组中选择了两种、三种或更多种病毒抗原的不同组合，即A35R、B6R、A29L、E8L、H3L和M1R。这些抗原是基于先前的正痘病毒研究数据和对其免疫原性潜力的评估而选择的。这些不同的mRNA疫苗在给小鼠注射后，产生了强大的免疫反应，包括抗体产生和偏向Th1的抗原特异性CD4+ T细胞反应。这些mRNA疫苗在减轻小鼠在接种高剂量牛痘病毒（VACV）感染后的体重减轻方面表现出极高的效力，并保护动物免受致命剂量的VACV挑战。多价mRNA疫苗特别设计为分别针对EV、MV或EV和MV表面蛋白，以研究它们的有效性和保护的分子基础。虽然对所有免疫原的强烈IgG反应得到了确认，但更高的累积IgG反应与暴露的免疫原数量更多的相关性表明，每种抗原在刺激免疫反应和根除VACV感染中的累积效应。此外，需要EV和MV抗原才能对致命剂量的VACV感染提供最强大的保护。最近，一种针对正痘病毒和SARS-CoV-2的单组分mRNA疫苗被巧妙地设计出来，并显示出保护免疫小鼠免受兔瘟病毒（ECTV）感染。这种疫苗候选物有潜力在同时增强对COVID-19的防御的同时产生抗正痘病毒的免疫力。这些开发工作为开发更强大、更安全的mRNA疫苗奠定了基础，以中和未来的猴痘爆发，这是控制爆发和保护公共卫生的重要一步。因此，mRNA疫苗技术成为应对猴痘等新兴传染病的强大工具。 利用mRNA疫苗的其他应用 从传统疫苗方法向mRNA技术的转变，现在正朝着解决各种传染病和人类健康障碍的方向发展，这突出了疫苗科学在保健方面的活力和适应力（图1B）。我们必须将历史见解与当代创新相结合，以保护全球健康免受各种医疗挑战。mRNA疫苗技术正在被利用和探索，以准备防御各种传染病，包括流感、寨卡病毒、呼吸道合胞病毒（RSV）、疟疾等。例如，针对流感的mRNA疫苗开发在诱导针对多种流感菌株的强大免疫反应方面显示出有希望的结果，包括季节性和大流行菌株。研究表明，mRNA技术在适应不断演变的流感病毒株和提供有效且可扩展的疫苗平台方面具有潜力。针对寨卡病毒的mRNA疫苗在临床前研究中显示出强大的免疫原性和保护作用，为控制寨卡病毒爆发提供了潜在策略。呼吸道合胞病毒（RSV）引起严重的呼吸系统疾病，威胁着全球数百万人民，特别是婴儿和老年人。Moderna的RSV mRNA疫苗（mRNA-1345）在临床研究中显示出有希望的结果。值得注意的是，最近报道了一种针对RSV和SARS-CoV-2感染的双价mRNA疫苗候选物，在小鼠和仓鼠中引发了强大的保护性免疫反应，防止了这两种传染病。 图1. mRNA疫苗技术和其应用。A，mRNA疫苗利用遗传蓝图（mRNA）来触发人体中的免疫防御。B，mRNA技术的发展，以及在防御传染病和其他应用中的应用。 除了传染病，癌症免疫疗法是mRNA疫苗技术的下一个前沿。可以设计mRNA疫苗以针对肿瘤抗原，激活免疫系统识别和摧毁癌细胞。BNT111、mRNA-4157、CV9202和BNT122是由BioNTech、CureVac和Moderna Therapeutics开发的mRNA疫苗的一些例子，针对在黑色素瘤、非小细胞肺癌（NSCLC）和胰腺癌中表达的肿瘤相关抗原或新抗原。它们通过引发肿瘤特异性免疫反应来消除肿瘤细胞，在单独使用或与其他治疗剂如检查点抑制剂联合使用时显示出巨大的治疗潜力。mRNA疫苗也有望治疗自身免疫疾病、过敏免疫疗法、再生医学、罕见遗传疾病等，通过调节免疫反应和针对致病因素。虽然针对这些疾病的mRNA疫苗仍处于早期开发阶段，但研究人员正在积极探索mRNA疫苗在这些领域的潜力。 mRNA疫苗技术的未来展望 mRNA疫苗的诞生是疫苗历史上的一个决定性时刻。mRNA疫苗技术在应对新出现的传染病方面的潜力已在COVID-19大流行中得到展示，并且通过迅速开发猴痘mRNA疫苗候选物得到进一步证明。mRNA疫苗技术正在迅速发展（图1B）。 环状RNA（circRNA）是一种形成共价闭合连续环的RNA类型，被用来代替mRNA编码抗原。circRNA在细胞中自然存在，比线性RNA更稳定，可以维持蛋白表达，减少重复剂量的需求。自复制RNA（saRNA）能在宿主细胞内自我复制，可以代替mRNA延长编码抗原的产生。saRNA通常具有来自RNA病毒的额外遗传元素，以实现自我复制。自我复制的特性允许更低的疫苗剂量，同时仍能实现有效的免疫刺激，减少疫苗接种的负担。 利用AI辅助设计优化mRNA序列可以提高蛋白表达水平，减少先天免疫系统的激活，并延长细胞内mRNA的半衰期，从而提高疫苗性能。通过计算模型微调mRNA结构和组成对最大化疫苗效力和安全性至关重要。正在探索新的和改进的脂质纳米颗粒（LNP）配方，以增强mRNA的摄取、细胞内释放和抗原表达。应探索针对特定细胞类型（如树突状细胞或淋巴细胞）的靶向LNP输送系统，以优化抗原呈递和免疫激活。未来的mRNA疫苗可能结合新的佐剂策略来增强免疫原性和提高效力。免疫刺激复合物（ISCOMs）、Toll样受体（TLR）激动剂、佐剂脂质体或细胞因子佐剂等佐剂技术可以与mRNA疫苗结合使用，以调节免疫信号通路并促进抗原特异性免疫记忆。针对特定疫苗目标和免疫概况量身定制佐剂配方，有望优化疫苗诱导的保护性免疫。 这些技术特点代表了正在进行的进步和令人兴奋的前景，用于下一代疫苗，这些疫苗在提高效力、稳定性和多功能性方面具有增强的特性，以应对传染病和其他健康挑战。 mRNA疫苗研究和分发的全球合作与传统疫苗开发相比，呈现出独特的挑战和考虑因素。围绕mRNA疫苗的知识产权格局，包括专利和专有技术，可能阻碍全球合作。在保护知识产权和促进技术共享及知识转移的需求之间取得平衡，对于促进合作研究和扩大全球mRNA疫苗获取至关重要。在全球部署方面，合作举措应促进监管协调、数据共享和相互认可批准，以简化疫苗授权并促进跨境分发。合作努力必须解决定价机制、许可协议和供应链物流问题，使mRNA疫苗对全球弱势社区负担得起且易于获得。 总之，mRNA疫苗技术的兴起标志着疫苗策略的新时代。合作举措和技术发展及转让在推进mRNA疫苗研究和确保公平分配以全球范围内应对传染病方面发挥着至关重要的作用。它不仅展示了对大流行应对的巨大潜力，而且还有潜力转变各种医学领域疾病治疗的方法。mRNA疫苗技术的持续发展可能会塑造疫苗开发和公共卫生的未来格局。 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

NEW YORK, NY, USA I October 22, 2024 I SIGA Technologies, Inc. (SIGA) (NASDAQ: SIGA), a commercial-stage pharmaceutical company and leader in infectious diseases, today announced that it entered into an agreement with Vanderbilt University to obtain a license to a portfolio of preclinical fully human monoclonal antibodies (mAbs) which could be used as potential treatments for a broad range of orthopoxviruses, including smallpox and mpox. Under the agreement, SIGA has exercised its option to license the exclusive rights to develop, manufacture, and commercialize these mAbs globally. “SIGA has cultivated deep expertise in orthopoxvirus, and we are thrilled to expand our pipeline with Vanderbilt’s human monoclonal antibodies, which nicely complement our best-in-class TPOXX ® franchise. We believe these antibodies hold the potential to treat a broad spectrum of orthopoxviruses, both as a therapeutic and a prophylactic measure. By leveraging our unique capabilities in clinical development and our long-standing partnerships with U.S. Government agencies, we are well-positioned to maximize the impact of these potential new therapies,” said Diem Nguyen, SIGA Chief Executive Officer. “This license marks a step forward in our strategy to leverage our existing capabilities to create new opportunities for growth over the long term.” Developed by James Crowe, Jr., M.D., Professor of Pediatrics, Pathology, Microbiology and Immunology at Vanderbilt University Medical Center, these mABs have demonstrated promise in preclinical models and could potentially be used as standalone treatments or in combination with TPOXX ® . The U.S. Department of Defense is currently funding the development of these mAbs as potential orthopoxvirus treatments through Phase 1 clinical trials under a contract awarded to a contract manufacturing organization with biologics expertise. “Given the need for additional orthopoxvirus treatments in these unsettling times of recurring poxvirus outbreaks, my team and I are excited to work with SIGA in its future efforts to advance the development of these innovative antibodies,” said Dr. Crowe. The financial terms of the transaction were not disclosed. About SIGA SIGA is a commercial-stage pharmaceutical company and leader in global health focused on the development of innovative medicines to treat and prevent infectious diseases. With a primary focus on orthopoxviruses, we are dedicated to protecting humanity against the world’s most severe infectious diseases, including those that occur naturally, accidentally, or intentionally. Through partnerships with governments and public health agencies, we work to build a healthier and safer world by providing essential countermeasures against these global health threats. Our flagship product, TPOXX ® (tecovirimat), is an antiviral medicine approved in the U.S. and Canada for the treatment of smallpox and authorized in Europe and the UK for the treatment of smallpox, mpox (monkeypox), cowpox, and vaccinia complications. For more information about SIGA, visit www.siga.com . SOURCE: SIGA