Chikungunya virus vaccine (Valneva)

摘要：基孔肯雅病毒疫情具有爆发性和不可预测性，严重影响人群健康和经济发展 。2023 年 11 月，美国 FDA 加速批准了一款基孔肯雅病毒减毒活疫苗 IXCHIQ；2025 年 2 月，美国 FDA 和欧盟委员会又分别批准了一款新的基孔肯雅病毒样颗粒疫苗 Vimkunya 。两项随机、双盲、安慰剂对照试验分别评估了 Vimkunya 在 12 - 64 岁和 65 岁及以上健康人群中的安全性和免疫原性。结果显示，疫苗耐受性良好，不同年龄段人群均产生了一定的免疫反应，但也存在研究人群代表性不足等局限 。Vimkunya 的获批是重要进展，后续还需开展更多上市后研究以明确其在不同人群中的效果。一、基孔肯雅病毒的危害与疫苗研发背景基孔肯雅病毒通过伊蚊在人群中传播，其引发的疫情往往来势汹汹且难以预测 。像 2015 年巴西爆发的疫情，预估病例达 100 万之多。虽然去年全球报告病例数为 62 万，但约 40 亿人生活在受威胁区域。感染该病毒后，患者会出现急性、使人衰弱的症状，持续约 2 周，主要表现为发热和严重关节疼痛。而且，31 - 57% 的感染者症状会持续数月，不少人还会发展成慢性关节疼痛，感染后 3 个月内死亡率更是会增加 4 倍。一旦爆发疫情，不仅会影响大量人群的健康，还会带来严重的经济损失 。为应对这一威胁，疫苗研发至关重要。此前，美国 FDA 在 2023 年 11 月加速批准了 IXCHIQ，这是一款针对 18 岁及以上人群的基孔肯雅病毒减毒活疫苗，但需要开展更多上市后研究 。而病毒样颗粒疫苗因不含遗传物质，无法自我复制，安全性较高。2025 年 2 月，美国 FDA 和欧盟委员会批准了针对 12 岁及以上人群的病毒样颗粒疫苗 Vimkunya 。二、Vimkunya 疫苗在 12 - 64 岁人群中的研究Jason Richardson 及其同事开展了一项随机、双盲、安慰剂对照试验，评估 Vimkunya 在 12 - 64 岁非流行地区健康人群中的安全性和免疫原性 。研究招募了 3258 名参与者，其中 2790 人接种疫苗，464 人接受安慰剂。参与者年龄中位数为 38 岁，分为 12 - 17 岁、18 - 45 岁、46 - 64 岁三个年龄组。疫苗含有来自基孔肯雅病毒塞内加尔株 37997 的 40µg 纯化病毒样颗粒（包括衣壳蛋白 C 和包膜蛋白 E1、E2）、300µg 佐剂氢氧化铝和无防腐剂及抗生素的稀释液，采用单剂量注射方式接种 。研究通过在第 8、15、22 和 183 天的随访评估不良事件，并检测基孔肯雅病毒中和抗体 。由于当前基孔肯雅病例较少，难以开展基于预防感染或发病的标准 3 期疗效试验，所以该试验主要基于保护生物标志物的刺激来评估安全性和免疫原性。此前 2 期试验中接种 Vimkunya 疫苗者的血清在非人灵长类动物被动转移实验中发现，中和滴度（NT80）达到 100 或更高可能预示着临床获益 。结果显示，疫苗耐受性良好 。疫苗组 2790 名参与者中有 1257 人（45.1%）报告了不良事件，安慰剂组 464 人中有 161 人（34.7%）报告了不良事件。但疫苗组中只有 3 人（0.1%）出现 3 级或以上与疫苗相关的特殊不良事件，其中 1 起事件可能与疫苗相关且被列为严重不良事件 。血清反应率在第 8 天为 46.6%，第 22 天升至 97.8%，到第 183 天仍有 85.5% 的参与者可检测到抗体。抗体峰值几何平均滴度在第 22 天为 1618，到第 183 天降至 337.73 。12 - 17 岁年龄组的抗体反应略高于 18 - 45 岁年龄组 。三、Vimkunya 疫苗在 65 岁及以上人群中的研究Lauren Tindale 及其同事进行了另一项研究，评估 Vimkunya 在 65 岁及以上人群中的安全性和免疫原性 。该研究招募了 413 名参与者，其中 206 人接种疫苗，207 人接受安慰剂。参与者年龄中位数为 70 岁，344 人（83%）有欧洲血统，49 人（12%）有非洲血统，242 人（59%）为女性，171 人（41%）为男性。研究设计与上述试验相似，主要临床终点相同，随访时间为第 15、22 和 183 天 。结果显示，该年龄组报告的总不良事件数比 12 - 64 岁人群更少，疫苗组和安慰剂组之间无显著差异，且未观察到严重的疫苗相关不良事件 。疫苗组进一步分为 65 - 74 岁和 75 岁及以上两个亚组，血清反应率虽低于 12 - 64 岁人群，但仍较高，在第 183 天为 75.5%，第 22 天为 87.3% 。第 22 天几何平均滴度为 723.93 ，第 183 天降至 233.02 。65 - 74 岁和 75 岁及以上两个亚组的血清学反应无显著差异 。四、研究的优势、局限与展望这两项研究的最大优势在于测试了广泛年龄段（12 岁到 75 岁以上）的参与者，并且在老年参与者中发现了良好的安全性 。然而，研究也存在一些局限性。一方面，具有与疫苗最可能使用的流行地区相似遗传背景的参与者占比很少；另一方面，尚未充分证明疫苗的临床获益 。总体而言，Vimkunya 疫苗的获批是基孔肯雅病毒防治领域的重要进展 。当未来全球任何地方再次爆发基孔肯雅疫情时，这款疫苗将为美国、欧盟旅行者及其他人群提供保护，随着更多国家监管机构的批准，其应用范围将进一步扩大 。此外，为了让低收入和中等收入国家也能使用这款疫苗，相关合作正在开展，以降低疫苗价格，提高可及性 。不过，还需要开展更多上市后研究，明确遗传背景和既往感染对疫苗反应的影响，进一步验证其临床效果，为全球防控基孔肯雅病毒提供更坚实的依据 。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不本站。

Saint Herblain (France), April 18, 2025 – Valneva SE (Nasdaq: VALN; Euronext Paris: VLA), a specialty vaccine company, today announced that during its regular meeting on April 16, the U.S. Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) updated its recommendation for use of Valneva’s single-dose chikungunya vaccine IXCHIQ® for the prevention of disease caused by the chikungunya virus (CHIKV). ACIP maintained its current recommendation for IXCHIQ® for persons aged ≥18 years traveling to a country or territory where there is a chikungunya outbreak. Additionally, it may be considered for persons aged ≥18 years traveling or taking up residence in a country or territory without an outbreak but with elevated risk for U.S. travelers if planning travel for an extended period of time e.g., six months or more. The ACIP also voted to recommend a precaution related to the use of IXCHIQ® in persons aged ≥65 years. This precaution is a response to an ongoing investigation by the CDC of six cases of serious adverse events (SAEs), including five hospitalizations, among persons aged 67-86 years after vaccination with IXCHIQ®. These SAEs were reported through the Vaccine Adverse Event Reporting System (VAERS), which is intended to be an early warning system to identify potential safety issues but generally cannot determine if adverse events are caused by a vaccine. All of the individuals who were hospitalized had pre-existing comorbidities, and ACIP concluded that while plausible, no causal association with IXCHIQ® could be determined for all cases and that further investigation is warranted. ACIP also noted that for individuals aged ≥65 years, vaccination with IXCHIQ® might be indicated in certain higher-risk settings (e.g., outbreak), given the known risks for severe chikungunya disease and hospitalization in this age group. For example, earlier this month Valneva supplied 40,000 doses of IXCHIQ® to France’s Island of La Réunion where the local public health agency, the Agence Régionale de Santé (ARS), is prioritizing vaccination of adults aged 65 and over, especially those with comorbidities, to protect residents during the ongoing chikungunya outbreak. Valneva recently received confirmation from ARS for an order of 50,000 additional doses of IXCHIQ® as part of its ongoing effort to manage this outbreak. To date, Valneva has supplied approximately 80,000 doses of IXCHIQ® in the United States, Canada and Europe. No further SAEs have been reported since January 2025 globally, and Valneva has not identified any safety signal concerns that are inconsistent with the U.S. product label through its ongoing post-marketing safety monitoring, including its periodic safety reports and routine signal detection activities, which are shared with the U.S. Food and Drug Administration (FDA). Juan Carlos Jaramillo, M.D., Chief Medical Officer of Valneva, commented, “Valneva is committed to the highest standards of safety, and the safety profile of IXCHIQ® remains unchanged and positive. We respect the ACIP recommendation and agree on the importance of continuing the stringent safety surveillance protocols that are in place. We encourage providers to assess the benefit/risk of vaccination based on the individual’s medical history and upcoming travel, in line with the current recommendation.” The recommendation from ACIP is pending final approval by the Director of the CDC and the U.S. Department of Health and Human Services. About ChikungunyaChikungunya virus (CHIKV) is a mosquito-borne viral disease spread by the bites of infected Aedes mosquitoes which causes fever, severe joint and muscle pain, headache, nausea, fatigue and rash. Joint pain is often debilitating and can persist for weeks to years1. In 2004, the disease began to spread quickly, causing large-scale outbreaks around the world. Since the re-emergence of the virus, CHIKV has now been identified in over 110 countries in Asia, Africa, Europe and the Americas2. Between 2013 and 2023, more than 3.7 million cases were reported in the Americas3 and the economic impact is considered to be significant. The medical and economic burden is expected to grow with climate change as the mosquito vectors that transmit the disease continue to spread geographically. As such, the World Health Organization (WHO) has highlighted chikungunya as a major public health problem.4 About Valneva SEWe are a specialty vaccine company that develops, manufactures, and commercializes prophylactic vaccines for infectious diseases addressing unmet medical needs. We take a highly specialized and targeted approach, applying our deep expertise across multiple vaccine modalities, focused on providing either first-, best- or only-in-class vaccine solutions.We have a strong track record, having advanced multiple vaccines from early R&D to approvals, and currently market three proprietary travel vaccines, including the world’s first chikungunya vaccine, as well as certain third-party vaccines.Revenues from our growing commercial business help fuel the continued advancement of our vaccine pipeline. This includes the only Lyme disease vaccine candidate in advanced clinical development, which is partnered with Pfizer, the world’s most clinically advanced Shigella vaccine candidate, as well as vaccine candidates against the Zika virus and other global public health threats. More information is available at www.valneva.com. Media and Investor Relations Contacts Laetitia Bachelot-FontaineVP Global Communications & European Investor RelationsM +33 (0)6 4516 7099laetitia.bachelot-fontaine@valneva.com Joshua Drumm, Ph.D.VP Global Investor RelationsM +001 917 815 4520joshua.drumm@valneva.com Forward-Looking Statements This press release contains certain forward-looking statements relating to the business of Valneva, including with respect to potential product sales and regulatory review of existing products. In addition, even if the actual results or development of Valneva are consistent with the forward-looking statements contained in this press release, those results or developments of Valneva may not be sustained in the future. In some cases, you can identify forward-looking statements by words such as “could,” “should,” “may,” “expects,” “anticipates,” “believes,” “intends,” “estimates,” “aims,” “targets,” or similar words. These forward-looking statements are based largely on the current expectations of Valneva as of the date of this press release and are subject to a number of known and unknown risks and uncertainties and other factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievement expressed or implied by these forward-looking statements. In particular, the expectations of Valneva could be affected by, among other things, uncertainties and delays involved in the development and manufacture of vaccines, unexpected clinical trial results, unexpected regulatory actions or delays, competition in general, currency fluctuations, the impact of the global and European credit crisis, and the ability to obtain or maintain patent or other proprietary intellectual property protection. Success in preclinical studies or earlier clinical trials may not be indicative of results in future clinical trials. In light of these risks and uncertainties, there can be no assurance that the forward-looking statements made in this press release will in fact be realized. Valneva is providing this information as of the date of this press release and disclaims any intention or obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. 1 https://jvi.asm.org/content/jvi/88/20/11644.full.pdf 2 https://cmr.asm.org/content/31/1/e00104-163 PAHO/WHO data: Number of reported cases of chikungunya fever in the Americas (Cumulative Cases 2018-2023 and Cases per year 2013-2017). https://www.paho.org/data/index.php/en/mnu-topics/chikv-en/550-chikv-weekly-en.html. Last accessed 01 Aug 2023.4 Geographical expansion of cases of dengue and chikungunya beyond the historical areas of transmission in the Region of the Americas (who.int) Attachment 2025_04_18_ACIP_PR_EN_Final