作者: Yu, Changming ; Fan, Pengfei ; Xia, Lingyun ; Chi, Xiangyang ; Wang, Xingxing ; Zhou, Qiang ; Huang, Ping ; Fang, Ting ; Cui, Yue ; Zhang, Guanying ; Sun, Hancong ; Li, Jianhua ; Zhang, Yuanyuan

SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv)₂ form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC₅₀ lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion.

2024-10-01·ANTIVIRAL RESEARCH

Nirmatrelvir and molnupiravir maintain potent in vitro and in vivo antiviral activity against circulating SARS-CoV-2 omicron subvariants

Article

作者: White, Kris M ; McGovern, Briana L ; van Bakel, Harm ; Rai, Devendra K ; Cardin, Rhonda D ; Leiva-Rebollo, Rocio ; Simon, Viviana ; Rodriguez, M Luis ; Rosales, Romel ; Sordillo, Emilia Mia ; García-Sastre, Adolfo ; Diaz-Tapia, Randy ; Anderson, Annaliesa S ; Benjamin, Jared

Variants of SARS-CoV-2 pose significant challenges in public health due to their increased transmissibility and ability to evade natural immunity, vaccine protection, and monoclonal antibody therapeutics. The emergence of the highly transmissible Omicron variant and subsequent subvariants, characterized by an extensive array of over 32 mutations within the spike protein, intensifies concerns regarding vaccine evasion. In response, multiple antiviral therapeutics have received FDA emergency use approval, targeting the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and main protease (Mpro) regions, known to have relatively fewer mutations across novel variants. In this study, we evaluated the efficacy of nirmatrelvir (PF-07321332) and other clinically significant SARS-CoV-2 antivirals against a diverse panel of SARS-CoV-2 variants, encompassing the newly identified Omicron subvariants XBB1.5 and JN.1, using live-virus antiviral assays. Our findings demonstrate that while the last Omicron subvariants exhibited heightened pathogenicity in our animal model, nirmatrelvir and other clinically relevant antivirals consistently maintained their efficacy against all tested variants, including the XBB1.5 subvariant.

2024-09-01·iScience

Immunogenicity of a third dose with mRNA-vaccines in the ChAdOx1-S/BNT162b2 vaccination regimen against SARS-CoV-2 variants

Article

CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

项与 JN-001 相关的新闻（医药）

2024-09-06

·赛柏蓝

大浪淘沙，新型mRNA疫苗强势崛起

特约作者 | 春胡责任编辑 | 郑瑶 8月份，全球疫苗格局正在经历一些重要的变化。一方面疫苗研发的多样性正在增加，技术平台的进步推动了重组蛋白疫苗、核酸疫苗和病毒载体疫苗等的发展。但另一方面，在大浪淘沙中部分疫苗因为种种原因，逐步走向衰退。 01 FDA批准新型mRNA COVID-19疫苗近日，FDA批准了辉瑞-BioNTech和Moderna公司生产的针对Omicron变体KP.2毒株的更新版mRNA COVID-19疫苗（2024-2025计划）的紧急使用授权（EUA）。报道称：更新的疫苗旨在更密切地针对当前流行的病毒变体，以预防COVID-19带来的严重后果，包括住院和死亡。 6月初，FDA向已获许可和授权的 COVID-19 疫苗制造商提出建议，指出2024-2025年的COVID-19 疫苗配方应采用单价JN.1疫苗。随着SARS-CoV-2病毒的持续变异和 COVID-19 病例数的上升，FDA进一步评估并建议制造商，2024-2025年配方的COVID-19 疫苗首选JN.1谱系为KP.2毒株。更新后的mRNA 新冠疫苗包括Comirnaty（辉瑞-BioNTech 生产）和Spikevax（ModernaTX Inc.生产），二者均获准用于12岁及以上的个人。此外， Moderna 新冠疫苗和辉瑞-BioNTech 新冠疫苗，二者均获准用于6个月至11岁的个人紧急使用。 FDA预计，除非出现传染性明显更强的SARS-CoV-2变异株，否则COVID-19疫苗的成分将需要每年进行评估，与季节性流感疫苗更新模式相似。 FDA生物制品评估与研究中心主任Peter Marks医学博士表示：“疫苗接种仍然是预防COVID-19的基石。这些更新的疫苗符合该机构严格的安全性、有效性和制造质量科学标准。鉴于人群因之前接触病毒和接种疫苗而产生的免疫力正在减弱，我们强烈建议符合条件的人考虑接种更新的COVID-19疫苗，以更好地预防目前流行的变异病毒。” mRNA新冠疫苗已在美国为数亿人接种，接种疫苗的获益仍然大于风险。接种更新版 mRNA COVID-19疫苗的个体可能会出现与之前接种mRNA COVID-19疫苗的个体报告的不良反应类似，这些不良反应与相应的处方信息或情况说明书中所述类似。更新版疫苗有望提供针对目前流行的变异株引起的COVID-19的保护。 02 欧盟撤销两款新冠疫苗 2024年8月9日，EMA更新撤销上市许可的COVID-19疫苗，陆续撤销阿斯利康、强生、赛诺菲等的新冠疫苗。 03 mRNA市场分析根据美国疾病控制与预防中心（CDC）的数据，2024年夏季COVID发病率被评估为“非常高”。部分原因可能与人们对以前疫苗和感染的免疫力减弱有关（以及新的传染性奥密克戎版本不断涌现）。因此，随着进入寒冷月份和呼吸道病毒季节，更新疫苗有望成为预防严重疾病的有效工具。 mRNA疫苗在未来15年内预计会在预防性疫苗领域占据主导地位。高开发成功率：mRNA疫苗具有更高的开发成功率，这是其相对于其他疫苗的一个显著优势。短期市场：短期内，预防性疫苗的收入主要来自COVID-19疫苗产品。中长期市场：从中长期来看，预计其他针对呼吸道合胞病毒和流感等疾病的疫苗将覆盖更广泛的人群，但疫苗价格上涨的空间有限。销售额预测：预防性mRNA疫苗（除COVID-19疫苗外）的全球销售额峰值预计约为8亿美元。个性化癌症疫苗产品的平均销售峰值预计约为50亿美元。针对单一疾病的mRNA疫苗产品销售峰值预计约为13亿美元。市场规模预测：到2035年，预防性mRNA疫苗（不包括COVID-19疫苗）的市场规模预计为70-100亿美元。包括COVID-19疫苗在内的整体市场规模预计为120-150亿美元。个性化癌症疫苗和针对单一疾病的疫苗整体市场规模（经风险调整）预计也将达到70-100亿美元。参考资料： 1.https://www.fda.gov/news-events/press-announcements/fda-approves-and-authorizes-updated-mrna-covid-19-vaccines-better-protect-against-currently 2.https://www.ema.europa.eu/en/human-regulatory-overview/public-health-threats/coronavirus-disease-cov 3.https://data-who-int.libproxy1.nus.edu.sg/dashboards/covid19/cases 4.https://www-nature-com.libproxy1.nus.edu.sg/articles/d41573-021-00147-y END 内容沟通：郑瑶（13810174402）医药代理商产品交流群扫描下方二维码加入银发经济市场机遇交流群扫描下方二维码加入左下角「关注账号」，右下角「在看」，防止失联

疫苗信使RNA紧急使用授权

2024-09-06

·生物制品圈

中国还没开始自费销售XBB的新冠疫苗，国外就要开始报废XBB的新冠疫苗了？！

根据CBC新闻和CTV新闻报道，由于针对新冠JN.1或KP.2毒株的更新疫苗预计将于10 月推出，加拿大卫生部已指示各省销毁针对 XB毒株形式供应的COVID-19疫苗。魁北克公共卫生主任告诉 CTV 新闻，目前的库存将退还给渥太华。萨斯喀彻温省已经处理了他们的 Moderna Spikevax XBB.1.5和辉瑞Comirnaty XBB.1.5 疫苗，以迎接新剂量的推出。联邦政府免疫指南上发布的一份通知称，针对XBB.1.5的疫苗在加拿大不再可用。针对现在占主导地位的JN.1或KP.2毒株的更新疫苗预计将“在未来几周内”获得批准。 “加拿大卫生部已指示所有省份遵循做法和流程，从2024年9月1日起移除和销毁所有现有的 XBB 疫苗库存。值得注意的是，为了替换被摧毁的疫苗，各省将很快收到针对目前在该国传播的 COVID-19 毒株的更新疫苗。“安大略省和其他省份预计将在10月收到加拿大卫生部的供应。”发言人说。此外，在近期美国FDA的一场询证会上，FDA专家建议今后仅供应JN.1的单价疫苗，而非包含既往流行株的新冠疫苗。而在辉瑞、莫德纳和Novavax公司最新推出的3款更新的新冠疫苗，均为单价疫苗。 7月份开始，中国多地开始了新冠疫苗自费省采工作。根据安徽省近期发布的《安徽省 2024 年新冠病毒疫苗及部分非免疫规划疫苗采购产品目录》，中标公示的几款新冠疫苗多为针对XBB株的单价或多价疫苗。智飞生物和万泰生物提供的为原始株的新冠疫苗，但万泰生物的鼻喷给药机制可产生针对其他变异株的广谱交叉保护作用。而在价格供应上，石药集团的mRNA新冠疫苗（XBB.1.5）售价高达598元为最高，但实际上康希诺的吸入式腺病毒载体新冠疫苗可能更高（XBB.1.5），三人份价格1114元，实际上较难凑齐三人同日接种。根据中国疾控中心7月1日至7月31日数据监测显示，全国31省主要流行株均为奥密克戎株。主要流行株为JN.1系列变异株和XDV系列变异株。根据采样日期，近4周JN.1及其亚分支占比分别为60.6%、58.3%、55.2%、56.1%，XDV及其亚分支占比分别为38.8%、40.4%、43.6%、43.4%。信息来源： https://www.cbc.ca/player/play/video/9.6500684 https://www.ctvnews.ca/health/health-canada-orders-provinces-to-destroy-old-covid-19-vaccines-amid-wait-for-new-batch-1.7025115 https://www.chinacdc.cn/jkzt/crb/zl/szkb_11803/jszl_13141/202408/t20240808_294292.html 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。

疫苗紧急使用授权信使RNA

2024-09-05

·PipelineReview

Moderna Receives Medicines And Healthcare Products Regulatory Agency (MHRA) Authorization For Updated COVID-19 Vaccine Targeting SARS-COV-2 Variant JN.1

Approval follows recommendation from global public health bodies to develop JN.1 COVID-19 vaccines At present, the JN.1 group of subvariants remain dominant in the UK The updated vaccine will be available for eligible groups as part of the NHS autumn vaccination program, and will also be available to purchase privately in the UK for the first time CAMBRIDGE, MA, USA I September 3, 2024 I Moderna, Inc. (Nasdaq:MRNA) today announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has authorized its updated COVID-19 vaccine targeting the JN.1 variant of SARS-CoV-2. Following the MHRA decision, doses will be available for eligible groups as part of the NHS autumn vaccination program, which is prioritized for use in people at greatest risk of serious illness from COVID-19. For the first time in the UK, the updated vaccine, Spikevax® JN.1, will also be available to purchase privately for those who are not eligible for the NHS Autumn vaccination program. The updated vaccine will be available from high street pharmacies, occupational health providers, and private healthcare companies. “As the SARS-CoV-2 virus continues to evolve, COVID-19 continues to present a serious health risk. Updated vaccines targeting circulating strains play a vital role in helping to protect those most at risk from severe illness and hospitalization, alleviating strain on the NHS,” said Darius Hughes, UK General Manager of Moderna. “With today’s approval from the MHRA, we are pleased that our updated COVID-19 vaccine will be available to the UK public, both through the NHS autumn vaccination program, as well as being available to purchase privately for the first time.” The approval follows guidance from the World Health Organization (WHO) Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC), which recommended that COVID-19 vaccines be updated to target the JN.1 family of Omicron subvariants for the 2024/25 vaccination campaign. At present, the JN.1 group of subvariants remain dominant in the UK. 1 About Moderna Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines. Moderna’s mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. SOURCE: Moderna Therapeutics

疫苗信使RNA上市批准紧急使用授权临床研究

100 项与 JN-001 相关的药物交易

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