Combined Pneumococcal Conjugate and Polysaccharide Vaccination in Inflammatory Rheumatic Disease. Impact of Antirheumatic Treatment on Antibody Response.

The overall objective of this project is to study the influence of modern anti-inflammatory treatments in established inflammatory rheumatic diseases (IRD) on antibody response elicited by pneumococcal vaccination using 13-valent conjugate vaccine in combined schedules with 23-valent polysaccharide vaccine. In addition, the aim is to study the clinical aspects of vaccination regarding: tolerability in immunosuppressed patients with IRD, impact on existing rheumatic disease, possible association with onset of new autoimmune diseases, long-term immunity following pneumococcal vaccination and efficacy in preventing invasive pneumococcal disease. Results from this study are expected to bridge the existing knowledge gap and contribute to body of evidence needed for recommendations and implementation of vaccination program in IRD patients.

开始日期2016-06-14

申办/合作机构

Region Skåne Holding AB

NCT03064620 / Unknown statusN/A

PICR-b Nasopharyngeal S. Pneumoniae and Nasal S. Aureus Carriage Study

Objective: PCV effects on S. pneumoniae and S. aureus carriage in a population based study. The major specific aims:
To compare different PCV vaccination policies, by cross-sectional repeated surveillance of closely related populations living in regions with different vaccination policies.
To compare the epidemiology, predictors and outcomes of antibiotic resistant S. aureus and S. pneumoniae in different regions of the PICR.
Study design: Annual / Biannual cross-sectional surveillance of nasal S. aureus carriage and nasopharyngeal S. pneumoniae carriage in children and one of their parents.

开始日期2014-04-01

申办/合作机构

Sheba Medical Center

[+1]

100 项与喷昔洛韦相关的临床结果

登录后查看更多信息

100 项与喷昔洛韦相关的转化医学

登录后查看更多信息

100 项与喷昔洛韦相关的专利（医药）

登录后查看更多信息

2,264

项与喷昔洛韦相关的文献（医药）

2024-12-31·Expert review of vaccines

Neoadjuvant personalized cancer vaccines: the final frontier?

Review

作者: Martin, William D ; De Groot, Anne S ; Richard, Guilhem ; Steinberg, Gary D ; Ruggiero, Nicole

INTRODUCTION:

Clinical trials of personalized cancer vaccines have shown that on-demand therapies that are manufactured for each patient, result in activated T cell responses against individual tumor neoantigens. However, their use has been traditionally restricted to adjuvant settings and late-stage cancer therapy. There is growing support for the implementation of PCV earlier in the cancer therapy timeline, for reasons that will be discussed in this review.

AREAS COVERED:

The efficacy of cancer vaccines may be to some extent dependent on treatment(s) given prior to vaccine administration. Tumors can undergo radical immunoediting following treatment with immunotherapies, such as checkpoint inhibitors, which may affect the presence of the very mutations targeted by cancer vaccines. This review will cover the topics of neoantigen cancer vaccines, tumor immunoediting, and therapy timing.

EXPERT OPINION:

Therapy timing remains a critical topic to address in optimizing the efficacy of personalized cancer vaccines. Most personalized cancer vaccines are being evaluated in late-stage cancer patients and after treatment with checkpoint inhibitors, but they may offer a greater benefit to the patient if administered in earlier clinical settings, such as the neoadjuvant setting, where patients are not facing T cell exhaustion and/or a further compromised immune system.

2024-05-01·Maternal and child health journal

Neighborhood Predictors of Poor Prenatal Care and Well-Child Visit Attendance

Article

作者: Richards, Alicia ; Sabo, Roy T ; Nelson, Bergen B ; Woolf, Steven H ; Krist, Alex H ; Wolf, Elizabeth R

Abstract:

Purpose:

Women and children continue to miss preventive visits. Which neighborhood factors predict inadequate prenatal care (PNC) and well-child visit (WCV) attendance remain unclear.

Description:

In a retrospective case–control study at Virginia Commonwealth University Health System, mothers with less than 50% adherence or initiation after 5 months gestation were eligible as cases and those with ≥ 80% adherence and initiation before 5 months were eligible as controls. Children in the lowest quintile of adherence were eligible as cases and those with ≥ 80% of adherence were eligible as controls. Cases and controls were randomly selected at a 1:2 ratio and matched on birth month. Covariates were derived from the 2018 American Community Survey. A hotspot was defined as a zip code tabulation area (ZCTA) with a proportion of controls less than 0.66. ZCTAs with fewer than 5 individuals were excluded. Weighted quantile regression was used to determine which covariates were most associated with inadequate attendance.

Assessment:

We identified 38 and 35 ZCTAs for the PNC and WCV analyses, respectively. Five of 11 hotspots for WCV were also hotspots for PNC. Education and income predicted 51% and 34% of the variation in missed PNCs, respectively; language, education and transportation difficulties explained 33%, 29%, and 17% of the variation in missed WCVs, respectively. Higher proportions of Black residents lived in hotspots of inadequate PCV and WCV attendance.

Conclusion:

Neighborhood-level factors performed well in predicting inadequate PCV and WCV attendance. The disproportionate impact impact of inadequate PCV and WCV in neighborhoods where higher proportions of Black people lived highlights the potential influence of systemic racism and segregation on healthcare utilization.

2024-03-01·Vaccine: X

Patterns of basic pneumococcal conjugated vaccine coverage in Ethiopia from 2015 to 2018; further analysis of Ethiopian DHS (2016–2019)

Review

作者: Motuma, Aboma ; Tolera, Moti ; Negash, Abraham ; Balis, Bikila ; Birhanu, Abdi ; Deressa, Alemayehu ; Getachew, Tamirat ; Abdurahman, Dureti ; Jibro, Usmael ; Mussa, Ibsa ; Mohammed, Fethia ; Demissie Regassa, Lemma ; Gamachu, Mulugeta

Background:

Geographic variation is crucial in spotting performance gaps in immunization programs, including the Pneumococcal Conjugated Vaccine (PCV). This will help speed up targeted vaccination and disease elimination programs in resource-limited countries. Thus, this study aimed to investigate the geographic variation and determinants of PCV vaccination coverage among children aged under five years old in Ethiopia.

Methods:

This analysis was carried out based on the 2016 and 2019 nationally representative Ethiopia Demographic and Health Survey (EDHS). We included two surveys of 10,640 children aged 12-23 months. The spatial analysis also covered 645 and 305 clusters with geographical information for both 2016 and 2019, respectively. We explored the spatial distribution, global spatial autocorrelation, spatial interpolation, and Stats Can windows of children with PCV-3 vaccination. P-values were generated using 999 Monte Carlo simulations to identify statistically significant clusters. To understand the coverage of PCV-3 in all areas of the country, we employed the ordinary Kriging interpolation method to estimate the coverage in unsampled areas. We also used hierarchical multivariate logistic regression to identify the factors associated with the utilization of the PCV vaccine (full vaccination).

Results:

Except for Addis Ababa, children in all regions have lower odds of receiving all three PCV vaccines compared to the Tigray region. Residence, sex of a child, mother's literacy status, household wealth index, and place of delivery were significant factors associated with receiving the third dose of PCV. Spatial analysis also showed the Somali and Afar regions had the lowest coverage, while the Addis Ababa and Tigray regions had higher coverage in both surveys.

Conclusion:

Even though the coverage of the full PCV vaccine improved from 2016 to 2019, variation was observed among regions and between rural and urban areas. The wealth index and educational status of mothers were the most important determinants of PCV vaccine utilization. Hence, the mass campaign might boost coverage in nomadic and semi-nomadic regions and rural areas. Similarly, programs that narrow the gap due to low socioeconomic differences should be formulated and implemented to increase uptake and general coverage.

项与喷昔洛韦相关的新闻（医药）

2024-06-18

·生物制品圈

HPV疫苗纳入国家免疫规划，仅剩一步之遥？

近期中国CDC研究人员根据全国免疫规划信息系统测算了2017-2022年的HPV疫苗累积接种率，研究指出我国HPV疫苗的首要优先接种人群——9-14岁（4%）女孩仍然最低，并给出了应当将HPV疫苗纳入国家免疫规划的建议。这条建议让社会各界对“HPV疫苗纳入免疫规划、所有适龄女孩免费接种HPV疫苗”生出许多猜想——中国疾控中心免疫技术工作组的建议，是迈向国家免疫规划（NIP，或扩大免疫规划EPI）的重要一步。近两年随着多省市已开展HPV疫苗免费接种、HPV疫苗集采价格“感人”的情况下，似乎HPV疫苗距离纳入NIP仅余一步之遥…… HPV疫苗纳入NIP，要走什么流程？ 2022年，一条卫健委经商教育部后对政协关于将水痘疫苗纳入国家免疫规划的提案答复函中指出了一款疫苗要纳入NIP需要的流程：《疫苗管理法》规定了我国在确定纳入免疫规划疫苗的种类时，需要由国家免疫规划专家咨询委员会综合考虑和论证传染病流行情况、疾病负担、疫苗的有效性和安全性、疫苗生产企业的供应能力、财政保障和社会效益等多方面因素，而后提出将有关疫苗纳入或退出国家免疫规划的建议，政府再根据国家免疫规划专家咨询委员会的建议调整国家免疫规划程序。而开头中国CDC关于9-45岁HPV疫苗接种率的研究似乎仅符合上述考虑“社会效益”的决策证据，同样的研究对五联苗、13价等疫苗也做过。专家咨询委员会的职责是什么？ 2017年10月，国家卫计委（卫健委前身）正式成立国家免疫规划咨询委员会（NIAC），赋予了NIAC具有将新疫苗纳入NIP的建言献策权利，2019年的《疫苗管理法》进一步保障了该组织的这项权力。根据国务院指导意见，NIAC的任务是提出建议——将合格、有效和负担得起的疫苗引入EPI目录，并确保获得更好的免疫服务。主要职责包括：（1）评估疫苗可预防疾病负担的证据以及新疫苗的安全性、有效性、卫生经济学以及生产和供应能力，以建议将其引入EPI；（2）更新当前EPI疫苗的建议；（3）就免疫规划策略和管理提供循证建议。比如首届委员会会议（2019年）主要探讨的就是修改国家免疫规划疫苗儿童程序（即2021年版程序）、百白破疫苗免疫程序调整、狂犬疫苗及被动制剂应用等内容。图源于北京大学第一医院官网：首届NIAC 成立会议根据委员会章程，委员会委员由27名来自不同领域的专家组成，专业领域包括：流行病学与卫生统计学、病原微生物学、疫苗学、临床医学（儿科、传染病﹑内科）、免疫学、卫生政策与卫生经济学、免疫预防实践等。这种以科学研究为基础，推动政府将新疫苗纳入免疫规划的循证决策模式，已在世界多国得到验证，比如美国的ACIP、英国的JCVI采用的都是类似模式。委员会会议基本流程是先由技术工作组对拟讨论议题的技术建议进行现场报告，专家咨询委员会委员进行质询和讨论，受邀参会的相关机构代表和相关领域专家发表意见后，有表决权的委员对技术工作组提交的建议进行表决，超过80%的参会委员赞成视为通过。因此按照流程，似乎只有中国疾控中心免疫技术工作小组综合宫颈癌和HPV的流行、疾病负担、HPV疫苗效果和安全性……等证据后，并发起“将HPV疫苗纳入国家免疫规划”的提议和相关报告，NIAC才能进行纳入免疫规划工作的评估和表决。 HPV疫苗近年能纳入国家免疫规划吗？ HPV疫苗国产化，为纳入国家免疫规划提供了基础条件，但这还不够。尽管各地在热火朝天的推进HPV疫苗惠民试点接种，国产二价的集采价格仍有下降空间，但有较大可能仍以目前的试点推广为主。从政策上来讲，彼时国家似乎已经有所研判——2023年1月国家十部委印发了《加速消除宫颈癌行动计划（2023-2030年）》，指出进一步推广适龄女孩HPV疫苗接种服务，鼓励有条件的地区开展HPV疫苗接种试点，不断提高HPV疫苗可及性，促进广大妇女健康。此外，在2023年7月十四届全国人大一次会议第2579、2762号建议的答复中也指出，工作思路仍然是整体推进、重点突破，积极推动有条件的地方将HPV疫苗接种纳入当地惠民政策。而从我国免疫规划疫苗的经费承担情况来看，HPV疫苗即使纳入国家免疫规划，国家财政也仅负担39%，地方财政（从省到县）负担了另外超过30%的比例（剩下的约30%由私营市场承担）。这也就意味着，无论HPV疫苗是否纳入NIP，地方财政都要承担相当比例的经费支出。而纳入疫苗越多，私营市场承担部分比例也就越低，财政承担比较就越高（筹资制度的弊端）。因此，若将PCV、Hib、轮状病毒、HPV等几种价格较贵的疫苗一同纳入NIP，则财政压力势必陡增（预算和分担比例双增）。而若仅纳入HPV疫苗，似乎又要证明其优先性优于PCV、Hib、轮状病毒等疫苗，这对NIAC来说可能也是一项具有挑战性的工作。除了NIAC建议外，各省也相继建立起了省级免疫规划专家咨询委员会，组织开展疫苗针对疾病监测、免疫规划政策调整论证等工作，会同省财政厅提出执行国家免疫规划有关疫苗调整的建议——这在广东、福建、江苏、江西等省已经实现。如果省级进行集中采购，HPV疫苗的价格也能触探到一些地区地方财政的可负担水平，而无需经过国家层面繁杂的程序流程。若以人口来算，目前开展区域性试点接种HPV疫苗的地区总人口已经超过了全国总人口的40%。因此，这未尝不是一种“曲线”策略。 HPV疫苗纳入免疫规划的挑战是什么？ 01/ 机制障碍近年来NIAC尚未考虑或建议纳入新疫苗，目前也尚不清楚NIAC如何与相关技术和行政部门合作，确定纳入该规划的优先疫苗。在NIAC成员组成里，我们未看到、也不清楚是否有来自宫颈癌诊疗领域内的妇科体系专家，或者如美国ACIP有性传播疾病或慢性病及癌症防控领域的专家，将HPV疫苗纳入免疫规划或许更依赖于免疫实践领域的专家发声。多位人大代表的呼声和倡议也更多是一种社会驱动力量，并非制度上的“建言献策”。我国既往纳入NIP的疫苗均为预防国家法定报告传染病的疫苗（这些疾病相对有系统的监测数据和循证证据），而呼声较高的轮状疫苗、Hib疫苗、水痘疫苗、PCV疫苗、HPV疫苗所预防疾病，均不在国家法定报告传染病目录内。 02/ 资金有限在NIP疫苗经费的分担上，筹资制度弊端明显但又不得已为之——除了中央政府承担39%外，财政状况普遍不良的县级也要承担近20%的比例——房地产行业不景气的环境下县级财政的压力更大，如果仍然按此比例承担，则任重道远。图源于网络此外还要考虑人员成本的费用，国家免疫规划经费中最大的支出并非疫苗而是人事（人事成本54% vs. 疫苗购买21%）。新疫苗的增加，不仅意味着购买疫苗的数量增加，也意味着在规范化和高质量发展的要求下，预防接种工作人员的劳动支出也将进一步增加。随着国家对服务水平、免疫规划信息化、数字化和智能化的要求，对人员场地、信息化设备、智能冷链设备的经费投入也将进一步增加。然而中国对每个孩子的疫苗支出成本和支出预算较低，据估计每名儿童不足100美元（可见总体预算不高、投入魄力可能不足），而美国为2000美元。投入不足，也就意味着疫苗企业缺乏向政府提供更低价格的动力。 03/ 循证证据有限与跨国制药企业在疫苗研发立项前、研究中、上市后即开始和持续开展流行病学、疾病负担等研究和证据积累不同，国内疫苗企业更多基于实用主义的调研——事件触发（如H1N1流行、手足口病流行等）、辖区防病需求（诺如、水痘、手足口病等烦不胜烦的流调）和公众需求潜力，缺乏基础证据积累。图源于网络以全球惟有我国未纳入EPI的Hib疫苗为例，其所预防疾病的疾病负担尤为欠缺且模糊。尽管NIAC在2018年和2019年对Hib疫苗进行了提案，但由于我国抗生素的广泛使用，导致关于Hib感染引起的疾病负担的高质量数据严重缺乏和被低估，相关证据仍在收集——但似乎这又是临床研究的冷门领域。我国关于HPV疫苗的整体证据数量既不多、质量也普遍不高，并且有一种被国外研究带着走的感觉。比如，对于HPV相关癌症负担的研究也高度依赖于国际机构（如ICO）“搜罗”的本土证据而非强有力的本土监测数据，导致我国竟拿不出国产二价是否“够用”的高质量证据。相比国外当前普遍在做HPV疫苗接种率干预、成本效益测算等积累纳入免疫规划证据的研究，中国仍然陷在一般人群HPV感染基因型分布的基础研究里——这并非疾病负担数据（非CIN+）。而在经费不足的情况下，减少疫苗接种剂次是必要途径。尽管WHO已经发布关于单剂接种建议，但我国仅有关于2剂程序效果（2剂在一些地区尚引起疑虑）而无单剂效果的循证证据，仍然让我国难以迈出那一步。总之，HPV疫苗距离纳入我国国家免疫规划虽有希望，但仍需静待下一个5年…… 参考资料： China CDC Wkly. 2024;6(19): 413-417. China CDC Wkly. 2019;1(2):28-30. http://www.nhc.gov.cn/wjw/tia/202201/5fa767ae769d4ba38ac460a581dd8336.shtml 国家免疫规划专家咨询委员会章程[J].中国疫苗和免疫,2018,24(05):608-609. https://www.chinacdc.cn/nip/ywdt2020/202404/t20240401_275306.html https://www.ndcpa.gov.cn/jbkzzx/c100008/common/content/content_1800703309280817152.html Vaccine. 2018 May 17;36(21):3041-3047. Lancet Public Health 2022; 7: e1064–72. 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

2024-06-11

·生物制品圈

同款疫苗，为何有人抗体不达标，几分原因在疫苗？

为什么有的人打完疫苗抗体不达标甚至测不到抗体？疫苗免疫程序是如何确定的？疫苗原因、个体差异通常是我们会考虑的因素，但这些可能还远远不够。一项大流行前发表、引用了582篇参考文献、发表在顶级学术刊物Clinical Microbiology Reviews（IF=36.8）上的鸿篇巨论，系统揭秘了影响疫苗免疫反应的8大类、超过40条影响因素。 8大类具体为：内在个体因素、围产期因素、外在因素、行为因素、营养因素、环境因素、疫苗自身因素、疫苗接种管理因素。 ps:内容经转译、极简压缩后呈现。 01 内在机体因素 01| 年龄是关键新生儿接种疫苗产生的抗体通常较低，且母体抗体也会干扰疫苗反应。此外，细胞介导的免疫反应、对T非依赖性多糖抗原的反应也都比较差。示例： 4-8周龄的婴儿口服脊灰疫苗（OPV）的血清保护率远高于出生7天内——100%vs.30-70%，同样在出生7天内接种第一剂百白破疫苗也比在6个月大时接种时效果更差。此外20项关于麻疹疫苗免疫反应的荟萃分析表明：4月龄 vs. 8月龄婴儿接种1剂麻疹疫苗的血清转换率为50% vs. 85%，前者抗体衰减速度也更快。 HPV疫苗也有类似发现，9-14岁及青春期女孩的抗体水平显著高于18岁以上成年女性，因此可以通过减少接种剂次获得相似免疫效果。老年人的疫苗反应通常更低、抗体下降速度也更快，他们对甲肝、乙肝、PPV23、流感疫苗、破伤风疫苗等的抗体应答较低。 02| 性别也有差别女性在登革热、甲肝、乙肝、Hib、IPV、狂犬病、天花、流感灭活疫苗有更高的抗体反应。但接种甲肝和PPV23疫苗后，抗体的下降速度也更快。此前曾有研究指出，女性在疫苗临床试验中接受了不必要的高剂量，导致与免疫炎症相关的不良事件可能更高。这也是有时候接种门诊会发现，夫妻同一天接种某疫苗后，妻子可能更容易出现免疫应答相关的炎症反应(如发热、疼痛等)。男性接种白喉、MCV-A、PCV7、PPV23和破伤风疫苗有更高的抗体反应。 03| 遗传学及共病因素等即使双胞胎也有差异，体液反应和细胞反应的遗传率存在差别，导致不同疫苗的免疫反应略有差异。血型抗原可以改变对感染的先天免疫反应，因此很可能会影响对疫苗接种的反应。有研究显示，O型血的人口服霍乱亚单位疫苗免疫应答效率可能更低。患有乳糜泻和糖尿病的儿童接种甲肝、乙肝疫苗的免疫应答水平更低，且抗体下降速度更快。糖尿病患儿对PPV23、麻疹、风疹疫苗的免疫反应也更低。接受血液透析的慢性肾功能衰竭成人对白喉、乙肝和破伤风疫苗的抗体反应较低，抗体下降更快，如果同时患有糖尿病时反应更差。儿童对II型脊髓灰质炎病毒的抗体反应较低。慢性肝病成人接种乙肝、甲肝疫苗后的GMTs较低，但有研究显示慢性乙肝人群接种戊肝疫苗的免疫原性与健康人群相似。患有慢性肝病的儿童在乙肝疫苗接种后GMTs也较低，但他们对IPV和白喉疫苗却有更高的抗体应答。 02 围产期因素 01| 出生周龄早产儿对疫苗接种的反应降低，主要是树突状细胞和巨噬细胞对病原体的识别减弱，T细胞活性、B细胞与T细胞的相互作用也较弱。与足月婴儿相比，早产儿接种首剂DTP后的抗体水平显著降低，即使是加强剂次后GMTs也更低。在初次接种白喉、HepB、Hib、PCV7、III型脊灰和百日咳疫苗后，GMTs也显著降低，抗体下降也更快。 02| 出生体重 2月龄、4月龄接种DTaP-Hib-IPV-HepB疫苗（六联疫苗）后一个月，3斤以下的婴儿GMTs低于3-4斤的婴儿。哪怕是在18-24月龄时给予加强针，出生体重低于3斤的婴儿对乙肝疫苗及其他疫苗的血清转化率仍然更低。出生体重较低与接种Hib疫苗的抗体衰减相关，但麻疹疫苗暂未发现这种相关性。 03| 喂养方式与人工喂养的婴儿相比，母乳喂养的婴儿接种白喉、Hib和OPV疫苗后血清IgG水平更高。然而一项荟萃分析发现，母乳喂养可能降低口服轮状疫苗（ORV）抗体应答。ORV接种前后停止母乳喂养一小时，对婴儿RV病毒特异性IgA的血清转换率没有影响。不同族裔的母亲，母乳中的IgA水平也有差异：印度女性的水平高于韩国和越南女性和美国女性。 04| 母传抗体母传抗体通常可抑制婴儿接种疫苗后的抗体反应。IPV或TDP初次免疫后，母体抗体水平提高2倍，婴儿接种后的GMTs值会降低约1/4。荟萃分析显示，母传抗体使麻疹疫苗的血清转换率降低了33.2%。孕产妇年龄是与孕产妇麻疹抗体水平相关的唯一因素。然而，婴儿体内对麻疹病毒的母亲抗体迅速下降，5月龄时只有12%。婴儿的甲肝母传抗体在前6个月很高，12月龄的婴儿快速下降到仅约37%的保护水平，没有母传抗体的婴儿在12-15个月时的GMTs显著高于6月龄内有母传抗体的婴儿。经胎盘转移及经母乳分泌的ORV母体抗体导致婴儿疫苗应答降低，转移给婴儿的母体抗体浓度/数量取决于几个因素：包括母体抗体水平、IgG亚型、胎龄和胎盘特征。妊娠期间接种破伤风、百日咳和流感疫苗可优化母体抗体的转移，因此目前建议孕期接种这些疫苗。不同妊娠阶段进行适当的疫苗接种时间也很重要的，如孕中期接种百白破疫苗导致的新生儿抗体明显高于孕晚期接种。 05| 孕期感染研究表明，母体感染疟疾寄生虫、丝虫病或钩虫可降低婴儿接种Hib疫苗、感染曼氏链球菌可降低婴儿对乙肝疫苗、感染疟疾可降低麻疹疫苗免疫应答率。与此相反，孕期母体感染斯特龙线虫与接种Hib、HepB 和百日咳毒疫苗后较高的抗体反应有关。妊娠期间使用阿苯达唑或吡喹酮进行感染治疗，并不影响婴儿对卡介苗、百白破、HepB、Hib、麻疹的免疫应答。 06| 其他母体因素母体体重指数越高，婴儿对卡介苗接种的细胞因子反应较低，母亲卡介苗疤痕的存在与婴儿接种卡介苗后较低的IL-5、IL-10和 IL-13反应有关。母亲营养不良与婴儿对 OPV 和 ORV 疫苗接种的抗体反应较低有关，但并不影响对肠道外疫苗的反应。孕期接触过HIV但未感染的婴儿，接种破伤风疫苗和卡介苗后，IFN-、IL-5 和 IL-13 反应较低，产前应用类固醇药物会降低婴儿对接种破伤风疫苗产生的抗体反应。 03 外在因素 01| 感染以新生儿常见的感染性腹泻和发热为例，研究虽然未发现对MMR疫苗抗体产生影响，但腹泻可能导致OPV疫苗免疫应答降低，发热可能导致Hib疫苗抗体降低。感染HIV的成年人在接种HepA疫苗血清阳转率较低，感染HIV的孕妇对BCG和破伤风疫苗接种的细胞因子反应较低。感染HIV的婴儿在接种BCG、麻疹和破伤风疫苗后细胞因子反应较低。 02| 抗生素、益生菌/益生元目前缺乏关于抗生素影响疫苗反应的人体试验数据，一些动物试验有显示可能存在影响。有报道称益生菌对白喉、HepA 、Hib、IPV、OCV、ORV、OPV和 TIV疫苗接种有有益作用，但益生菌类型、剂量以及服用的持续时间存在较大差异。 03| 微生物群长双歧杆菌对卡介苗、乙肝、灭活脊灰病毒、口服脊灰病毒和破伤风疫苗接种的抗体或细胞疫苗反应较高有关，而假单胞菌对这些疫苗的反应较低。厚壁菌门细菌与婴儿对ORV的体液反应、成人对伤寒沙门氏菌的细胞反应较高有关。一些微生物群与疫苗反应呈正相关——接种鼻喷流感疫苗者，鼻腔流感病毒IgA水平与螺旋乳杆菌、黑原菌、婴儿链球菌和细孔菌的群落水平呈正相关。 04| 预存抗体破伤风抗体滴度较高的个体在加强免疫后的免疫应答更强，Hib也有类似情况。但预存的白喉抗体反应则不受影响，而对其他分枝杆菌的预存抗体可能抑制卡介苗的免疫反应。流感病毒预存抗体也会增强免疫应答，而如果老年人此前没有预存抗体，接种流感疫苗后可能不会发生血清阳转。此外，对黄热病度的预存抗体可能会使接种登革热疫苗抗体显著增强，但对乙肝病毒的预存抗体，则使接种乙肝疫苗者出现不统一的研究结果。 04 行为因素 01| 吸烟许多研究发现，吸烟可能导致许多疫苗免疫应答降低。吸烟虽然不会导致HPV疫苗的免疫应答水平降低，但可能增加疫苗接种后产生低亲和力抗体的风险。吸烟可导致减毒流感疫苗的血清阳转率增强，但吸烟者接种减毒或灭活流感疫苗后的抗体下降速度也更快。 02| 饮酒酒精不会影响甲肝、乙肝疫苗的免疫应答，但会影响肺炎球菌疫苗的抗体水平——酗酒者接种PPV23肺炎多糖疫苗的血清型3、4、7F、8、19F的血清阳转率更低。 03| 运动参加马拉松长跑者的破伤风疫苗抗体水平更高，铁人三项运动员运动后接种破伤风、白喉、PPV23疫苗的抗体水平与非运动员无差异。接种前45分钟使用过测力计（某健身器材）的女性，接种流感疫苗的H3N2型抗体水平更高。有体力活动习惯的老年群体，接种流感疫苗的抗体水平优于久坐群体。研究表明，细胞因子的增加与臂围的增加相关，女性也会因此产生更多抗体。但是不同的流感灭活疫苗株通过运动增加的抗体反应各不相同，免疫原性较低的毒株通过运动增强的抗体反应更为敏感。 04| 情绪变化或应激接种流感疫苗当天，心情好的老年群体抗体水平可能更高。而女性如果接种流感疫苗前精神压力紧张，H3N2型的GMTs水平更高，男性则是MCV-A疫苗。 05| 慢性心理压力许多研究报告了疫苗免疫反应与慢性心理压力间的负相关关系，例如，因照顾患有痴呆症的伴侣或亲属而承受压力的老人，接种灭活流感疫苗和PPV23的抗体反应较低。感受到压力大、生活事件紧张或孤独的成年人在接种灭活流感疫苗后的抗体反应和细胞反应也较低。拥有较好的社会和家庭支持者，接种流感疫苗和乙肝疫苗的免疫反应较高。有压力生活事件、慢性压力和心理健康水平低的年轻人对HepB和MCV-C疫苗接种有较低的抗体反应。有研究显示，具有内在化情绪症状（抑郁或焦虑症状）的儿童对4价流脑结合疫苗有较高的抗体反应。 06| 睡眠接种疫苗前1周，如果睡眠时间较短（非主观上的睡眠质量），则接种甲肝、乙肝、灭活流感疫苗的免疫反应可能更低。但打鼾、阻塞性睡眠呼吸暂停的睡眠障碍者，未发现接种灭活流感疫苗抗体有差异。本章重点介绍疫苗自身因素（07节，型别、菌株/毒株、佐剂、剂量）和疫苗管理因素（08节，免疫程序、接种部位、接种途径、同时接种、药物作用等）。 05 营养因素 01| 肥胖/营养过剩肥胖个体的特异性CD8+T细胞更少，IFN-γ的产生也更少。对成人接种疫苗的诸多研究发现，BMI指数高的成人接种甲肝、乙肝疫苗免疫应答较弱。但接种灭活流感疫苗则有不同发现，BMI指数高者前期免疫应答较强，超过12个月后下降更快。图源于网络 02| 营养不良多数疫苗的免疫应答不会受到营养不良的影响。然而有报道指出，营养不良的儿童对乙肝、麻疹、OPV、百日咳、破伤风疫苗甚至卡介苗疫苗的抗体反应较低。 03| 微量元素（Vit A/D/E/Zn）维D在先天、体液和细胞免疫反应中起着重要的作用，但它在影响疫苗应答方面的作用尚不清楚。多数研究未发现维D缺乏与灭活流感疫苗免疫反应间的关联，但一些研究显示维D缺乏的儿童对灭活流感疫苗血清阳转率有下降趋势。在成人透析患者中，肠外骨化三醇治疗可导致流感疫苗抗体反应升高。此外，血液透析患者中维D缺乏可能导致乙肝疫苗免疫受挫。接种破伤风疫苗前补充维D可增强免疫应答，婴儿接种卡介苗前补充维D也能增强结核菌素皮肤反应。此外，发展中国家的肠炎可能降低口服类疫苗的免疫反应，如OPV、ORV疫苗。 06 环境因素 01| 城乡环境生活在农村地区的儿童对破伤风疫苗免疫反应相比城市儿童更为强烈，但对灭活流感疫苗、乙肝疫苗的免疫反应要弱于城市地区。 02| 地理位置生活在发展中国家的儿童对Hib、白喉、PCV7和百日咳疫苗接种的抗体反应较高，但对麻疹、OCV（口服霍乱疫苗）、OPV和伤寒沙门氏菌疫苗接种的抗体反应较低，发展中国家的成年人对乙肝疫苗接种的抗体反应较低。图源于网络 03| 季节/时节季节接种月与百日咳、PPV23、狂犬病和伤寒沙门氏菌疫苗接种抗体应答之间存在关联，与白喉、乙肝和破伤风疫苗接种抗体应答之间没有关联。雨季出生的非洲婴儿比在旱季出生的婴儿对卡介苗的应答更强。青少年在夏季接受第1剂、第2剂乙肝疫苗的个体GMTs低于在冬季接受疫苗的人。 04| 家庭规模共同生活的家庭成员人数越多，Hib疫苗的抗体应答似乎越高。 05| 毒素暴露一项研究表明，接种MMR疫苗后，早期砷暴露导致腮腺炎病毒抗体水平下降。也有研究表明，产前和哺乳期暴露于多氯联苯和二恶英会导致婴儿对麻疹和腮腺炎病毒的抗体反应降低。 07 疫苗因素 01| 疫苗类型、产品和菌株不同疫苗类型和产品的免疫反应差异很大。例如，即使是在接种1剂后，活疫苗通常会引起更强的疫苗反应，甚至终身保护。而灭活疫苗、亚单位疫苗或类毒素疫苗通常需要多剂，包括加强剂，以实现与活疫苗相似的保护。图源于网络：mRNA 多糖疫苗仅能诱导一种T细胞介导的独立疫苗反应，它不诱导免疫记忆、免疫反应比较短暂。这种疫苗对2岁以下的儿童没有保护作用，也不能减少鼻咽部的病菌携带。相比之下，多糖-蛋白结合疫苗具有优越的免疫原性，可以保护2岁以下的婴儿，并减少鼻咽部的携带。对针对同一疾病的类似疫苗的反应也可能因特定产品或菌株而异。例如，卡介苗、HepB、TIV、PCV7、狂犬病和麻疹疫苗已经证明了这一点。 02| 疫苗佐剂在疫苗中添加佐剂能够引起更强的免疫反应。根据疫苗中添加佐剂的类型、剂量，疫苗的免疫反应大小和质量也有较大差异。例如，新型佐剂MF59增加了抗体亲和力和对灭活流感疫苗的交叉保护；与使用铝佐剂的乙肝疫苗、HPV疫苗相比，含有新佐剂AS04的疫苗诱导了更高的血清转化率和GMTs。一项研究甚至发现，使用佐剂的三价流感疫苗，可产生针对B/Yamagta系的四价流感疫苗类似的血清保护抗体。 03| 疫苗剂量一项关于IPV疫苗的研究表明，给药剂量和抗体反应之间存在线性关系。此外，也可以通过增加ORV疫苗剂量来克服经胎盘或母乳转移的母体抗体的抑制作用。在接种乙肝疫苗的青少年群体中，以低于常规剂量20ug的一半剂量——10ug就足以诱导足够的血清保护，但GMTs和阳转率较低。在终末期肾病患者中，80ug乙肝疫苗增加了保护性抗体的持久性。然而对于Hib疫苗，即使剂量减少到正常的1/8，也能导致足够维持长期免疫的抗体滴度。研究表明，老年人接种高剂量灭活流感疫苗可产生较高的抗体反应，且相对保护效力也有所提升。在18-49岁的成年群体中，通常标准剂量就可以导致类似的血清转化率和GMTs，特别是在女性群体。 08 疫苗管理因素 01| 免疫程序影响疫苗反应的另一个关键因素是疫苗接种程序或间隔。延长接种间隔，通常会导致更高的免疫反应。例如，2月龄接种首剂、4-6月龄第二剂，DTP疫苗的抗体反应明显高于3-4月龄接种第二剂的免疫反应。同样，3月龄开启首针、5-9月龄续针时，DTP疫苗的抗体反应高于2月龄首针、3-4月龄续针。接种乙肝疫苗，首剂和第二剂或第二剂与第三剂的接种间隔延长，也与更高的GMTs和血清转化率有关。然而也有一些不一致的研究，0-12-24月程序接种乙肝疫苗的GMTs显著低于0-1-6月程序。相比之下，按0-1/12月程序接种甲肝疫苗的GMTs高于0-6/12个月程序或0-1/2个月程序。接种两剂MMRV的婴儿中，当接种间隔由4周延长为12个月时，GMTs对疫苗中的麻疹、风疹、腮腺炎、水痘病毒的免疫反应都更高。但流感疫苗例外——当给＜24月龄的儿童接种流感疫苗时，如果春季作为启动程序接种了第一针，然后在秋季接种第二针，则抗体反应与两针都在秋季接种没有统计学差异。 02| 接种部位成人臀部接种乙肝疫苗比在上臂接种时获得的应答更低（当然成人脱了裤子打疫苗也确实不雅观，毕竟接种门诊不是“成人”门诊）。此外涉及狂犬疫苗更是慎重，WHO立场文件指出，不建议狂犬疫苗使用臀围接种，因为臀围接种的免疫保护可能不太牢靠。但婴儿的情况却并非如此。研究发现，上臂三角肌接种Hib疫苗的儿童，与大腿外侧和臀部接种的GMTs没有统计学差异。（所以儿童能够脱了裤子接种，成人不能？） 03| 接种途径肌肉接种灭活流感疫苗比皮下接种可产生更高的抗体反应，但两种接种途径对白喉、PPV23或破伤风疫苗的抗体反应没有差异。图源于网络：肌内、皮下、皮内注射对于乙肝疫苗、狂犬疫苗来说，低剂量的皮内注射诱导的抗体反应类似于大剂量的肌肉注射。肌肉内疫苗接种依赖于T细胞介导的反应，而皮内疫苗接种激活树突状细胞介导的反应，后者在较低剂量下就可实现。研究发现，对肌内接种乙肝疫苗没有反应者，可能对皮内接种有免疫反应。皮内注射5ug甚至比肌内注射40ug的血清转化率更高。但4ug可能是个cut-off值，同时对半减量（2ug皮内vs. 20ug肌内）接种，皮内免疫反应要低于肌内，但两者的血清转化和抗体达峰时间没有差异。 04| 早/中/晚接种时间目前虽然有发现一天中什么时候接种疫苗可能会影响免疫反应，但相关研究结果却存在矛盾点。有研究表明，早上接种流感疫苗者的H1N1型抗体应答明显较高，对乙流也有较高的应答趋势，但对H3N2型无影响。另一项研究虽然也有类似发现，但仅局限在男性群体，包括甲肝疫苗。 05| 同时接种大量研究调查了同时接种活疫苗对疫苗反应的影响。两项荟萃分析总结了随机对照试验，比较了接受一剂MMRV或MMR和V作为单独疫苗的婴儿的疫苗反应。第一项荟萃分析纳入10项随机对照试验，但没有发现GMTs与其中任何疫苗成分有统计学差异。但在第二项纳入24项随机对照试验的荟萃分析显示，在9至24月龄的儿童中单独接种疫苗后，接种MMRV和同时接种MMR和V（MMR+V）或MMR的婴儿之间抗腮腺炎和水痘病毒的GMTs具有可比性。图源于网络相比之下，接受MMRV联苗的个体对麻疹病毒的GMTs明显高于接受同时接种两款疫苗或单独接种MMR的个体。但前者对风疹病毒的GMTs减少。MMRV的血清转化率也低于两款疫苗同时接种或单独接种MMR，这可能与早期疫苗中较低的病毒抗原剂量相混淆。黄热病疫苗与MMR疫苗同时接种可能导致血清转化率比间隔1个月分别接种更低（61% vs.71%的腮腺炎，90% vs. 97%水痘，70% vs. 87%YF），麻疹血清转化率不受同时接种的影响。研究显示，MMR或V疫苗与其他非活疫苗（含灭活、重组、亚单位等工艺的疫苗，如甲肝、PCV、Hib、MCV、DTaP-HBV-IPV-Hib）同时接种，并不影响任何疫苗的免疫反应。研究显示，新生儿同时口服OPV和ORV疫苗会干扰免疫应答。但当婴儿达到3月龄以后，同时服用OPV和ORV将不再影响疫苗应答。 06| 药物相互作用一项综述总结了13项随机对照试验，调查了预防性退热治疗的影响，发现扑热息痛会降低婴儿对所有的肺炎球菌血清型、Hib、白喉、破伤风和百日咳素的免疫应答，即使是使用了加强剂量也存在该现象，但对HepB或IPV没有影响。一项研究调查了疫苗接种前后使用布洛芬的效果，研究表明，接种前后使用布洛芬对初次接种破伤风疫苗时免疫应答降低，但在加强剂量后该现象消失，接种PCV疫苗的免疫反应不受影响。此外，最近一项针对老年人的大型研究表明，使用他汀类药物的可使灭活流感疫苗的GMTs降低。同样，接受地塞米松治疗慢性肺部疾病的早产儿在基础免疫后对Hib疫苗的免疫反应也显著降低。 07| 异源序贯该部分原文献未综述，笔者仅作简单示列（精力有限…）。目前关于异源序贯的研究较多的为新冠疫苗，多项临床研究均发现异源/不同工艺的新冠疫苗进行序贯接种，可诱导更广泛的体液免疫反应，进而可诱导更广泛、更高水平的中和抗体。图源于网络：新冠疫苗混合免疫不同价次的HPV疫苗也可以视为异源混合免疫，但相关研究较少。在一个两剂程序、混合使用二价和九价HPV疫苗进行免疫的临床研究显示，全程接种两剂九价、首剂九价&二剂二价或首剂二价&二剂九价的血清转化率均达100%。但HPV16/18在两个异源程序中的GMTs均优于两剂九价程序，但异源程序中的其他7种型别GMTs均劣于两剂九价程序，但不清楚是否具有长期意义。图源于文献4 在同时流行的疫苗可预防疾病中，也可视为另外一种形式的异源接种，如寨卡病毒灭活疫苗、日本乙脑疫苗和黄热病疫苗均在非洲同期流行，结果显示寨卡灭活疫苗在未暴露黄热病毒的成人和接种过日本脑炎或黄热病疫苗的成人中耐受性良好，但根据既往黄病毒疫苗接种状态，免疫原性有显著差异。资料来源： Clin Microbiol Rev. 2019 Mar 13;32(2):e00084-18. Vaccine. 2023 Oct 26;41(45):6645-6653. J Infect. 2023 Sep;87(3):242-254. Vaccine. 2018 November 12; 36(46): 7017–7024 Lancet Infect Dis. 2023 Oct;23(10):1175-1185. 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。

疫苗临床研究信使RNA

2024-05-08

·GlobeNewswire-Health Care

Vaxcyte Reports First Quarter 2024 Financial Results and Provides Business Update

-- VAX-31 Adult Phase 1/2 Study Enrollment Completed; Topline Safety, Tolerability and Immunogenicity Data Expected in Third Quarter of 2024 -- -- Following VAX-31 Adult Phase 1/2 Study Readout, Vaxcyte to Advance VAX-24 or VAX-31 to Adult Phase 3 Program -- -- VAX-24 Infant Phase 2 Study Enrollment Completed; Topline Data from Primary Immunization Series Expected by End of First Quarter of 2025, Followed by Topline Data from Booster Dose by End of 2025 -- -- $1.9 Billion in Cash, Cash Equivalents and Investments as of March 31, 2024, Including Net Proceeds of $816.5 Million from February Public Offering -- SAN CARLOS, Calif., May 08, 2024 (GLOBE NEWSWIRE) -- Vaxcyte, Inc. (Nasdaq: PCVX), a clinical-stage vaccine innovation company engineering high-fidelity vaccines to protect humankind from the consequences of bacterial diseases, today announced financial results for the first quarter ended March 31, 2024, and provided a business update. “We continue to make meaningful progress across our business, including for our pneumococcal conjugate vaccine (PCV) candidates, VAX-24 and VAX-31, which are intended to deliver the broadest spectrum of coverage against invasive pneumococcal disease (IPD),” said Grant Pickering, Chief Executive Officer and Co-founder of Vaxcyte. “We remain on track to announce the VAX-31 adult Phase 1/2 study topline safety, tolerability and immunogenicity data in the third quarter of this year, following which we plan to advance either VAX-24 or VAX-31 into Phase 3 clinical development in adults. Additionally, with enrollment completed in the VAX-24 infant Phase 2 study, we expect to deliver topline data from the primary immunization series by the end of the first quarter of 2025. Together, these two milestones will provide significant insight into our PCV franchise’s ability to achieve its full potential across the adult and pediatric populations.” “We closed the first quarter with a strong balance sheet bolstered by $816.5 million in net proceeds from the follow-on equity offering in February, propelling advancement of our PCV franchise and the scale-up of our manufacturing infrastructure,” said Andrew Guggenhime, President and Chief Financial Officer of Vaxcyte. “We also continue to progress our early-stage pipeline led by VAX-A1, a vaccine candidate designed to prevent Group A Strep infections. We believe our cell-free platform has the potential to enable the development of first-in-class vaccines to prevent or treat bacterial infections, which have serious and costly health consequences when left unchecked.” Key First Quarter Highlights PCV Franchise Adult Indication: Completed Enrollment of Phase 1/2 Study Evaluating VAX-31 for the Prevention of IPD in Adults Aged 50 and Older: In January 2024, Vaxcyte announced the completion of enrollment in its Phase 1/2 clinical study evaluating VAX-31, a 31-valent PCV candidate designed to prevent IPD, in healthy adults. This is a randomized, observer-blind, active-controlled, dose-finding study designed to evaluate the safety, tolerability and immunogenicity of VAX-31 at three dose levels (low, middle and high) compared to Prevnar 20® (PCV20) in 1,015 healthy adults aged 50 and older. VAX-31, the broadest-spectrum PCV in the clinic, has the potential to address a significant public health need by covering approximately 95% of IPD circulating in the U.S. adult population while maintaining coverage of previously circulating strains that are currently contained via ongoing vaccination. Additional information about the study can be found at www.clinicaltrials.gov under the identifier NCT06151288. PCV Franchise Infant Indication: Completed Enrollment of Phase 2 Study Evaluating VAX-24 for the Prevention of IPD in Infants: In March 2024, Vaxcyte announced the completion of enrollment in its Phase 2 clinical study evaluating VAX-24, a broad-spectrum, carrier-sparing 24-valent PCV candidate designed to prevent IPD, in healthy infants. The Phase 2 clinical study, which enrolled 802 healthy infants, is a randomized, observer-blind, dose-finding two-stage clinical study evaluating the safety, tolerability and immunogenicity of VAX-24 in infants. The Stage 1 portion of the study evaluated the safety and tolerability of a single injection of VAX-24 at three dose levels (low dose/1.1mcg, middle dose/2.2mcg, mixed dose/2.2mcg or 4.4mcg) and compared to VAXNEUVANCE™ (PCV15), which was the broadest-spectrum PCV at the time of study initiation, in 48 infants. The Stage 2 portion, which commenced in July 2023, is evaluating the safety, tolerability and immunogenicity of VAX-24 for the prevention of IPD at the same three dose levels and compared to PCV20, currently the broadest-spectrum PCV recommended by the Advisory Committee on Immunization Practices (ACIP). Participants who received VAX-24 in Stage 1 will continue the standard dosing regimen as part of Stage 2 and will be included in the safety, tolerability and immunogenicity analysis of the study. Additional information about the study can be found at www.clinicaltrials.gov under the identifier NCT05844423. Equity Financing: Completed Successful $862.5 Million Follow-On Financing, Further Strengthening Vaxcyte’s Balance Sheet: In February 2024, Vaxcyte completed an underwritten public offering of 12,695,312 shares of its common stock, which included the full exercise of the underwriters’ option to purchase additional shares, at a public offering price of $64.00 per share and pre-funded warrants to purchase 781,250 shares of common stock at a public offering price of $63.999 per underlying share. The aggregate gross proceeds to Vaxcyte from this offering were $862.5 million, before deducting underwriting discounts and commissions and other offering expenses payable by Vaxcyte. Anticipated Key MilestonesVaxcyte is advancing the clinical development of its PCV programs with several anticipated key upcoming milestones: PCV Franchise Adult Indication: Announce topline safety, tolerability and immunogenicity data from VAX-31 adult Phase 1/2 study in the third quarter of 2024.Following VAX-31 data, advance either VAX-24 or VAX-31 to an adult Phase 3 program. If VAX-24: Initiate Phase 3 pivotal, non-inferiority study in adults aged 50 and older in the second half of 2024 and announce topline safety, tolerability and immunogenicity data in the second half of 2025.Initiate balance of expected Phase 3 studies in 2025 and 2026. If VAX-31: Initiate full complement of expected Phase 3 studies in 2025 and 2026. PCV Franchise Infant Indication: Announce topline safety, tolerability and immunogenicity data from VAX-24 infant Phase 2 study primary three-dose immunization series by the end of the first quarter of 2025, followed by topline data from the booster dose by the end of 2025. Upcoming May and June Investor Conferences Company management will participate in fireside chats and host one-on-one meetings at the following investor conferences, and a live webcast of the fireside chats will be accessible through the Investors & Media section of the Company’s website at http://investors.vaxcyte.com for approximately 30 days following each conference: Bank of America Securities Health Care Conference, May 14-16, 2024: Fireside chat will take place live on Tuesday, May 14 at 9:20 a.m. PT / 12:20 p.m. ET.Jefferies Global Healthcare Conference, June 5-6, 2024: Fireside chat will take place live on Wednesday, June 5 at 8:30 a.m. PT / 11:30 a.m. ET. First Quarter 2024 Financial Results Cash Position: Cash, cash equivalents and investments were $1,899.8 million as of March 31, 2024, compared to $1,242.9 million as of December 31, 2023. The March 31, 2024 amount includes the $816.5 million in net proceeds from the follow-on offering completed in February 2024.Research & Development (R&D) Expenses: R&D expenses were $94.6 million for the three months ended March 31, 2024 as compared to $58.1 million for the same period in 2023. The increase was due primarily to higher expenses related to the ongoing VAX-31 adult and VAX-24 infant clinical studies, higher manufacturing expenses related to the planned VAX-24 or VAX-31 adult Phase 3 clinical trials and the potential commercial launches of the Company’s PCV programs, initially in the adult population, as well as an increase in personnel expenses related to the growth in the number of R&D employees.General & Administrative (G&A) Expenses: G&A expenses were $19.9 million for the three months ended March 31, 2024 as compared to $13.1 million for the same period in 2023. The increase was due primarily to higher personnel expenses related to the growth in the number of G&A employees.Net Loss: For the three months ended March 31, 2024, net loss was $95.0 million, compared to $60.5 million for the same period in 2023. Commercial Manufacturing Suite: In the first quarter of 2024, Vaxcyte incurred an additional $15.3 million in capital and facility buildout expenditures related to the ongoing construction of the dedicated manufacturing suite at Lonza intended to support the potential global commercialization of the Company’s PCV programs. As of March 31, 2024, Vaxcyte had incurred $101.8 million in total capital and facility buildout expenditures that were reflected on the Company’s balance sheet as of that date. About Vaxcyte Vaxcyte is a vaccine innovation company engineering high-fidelity vaccines to protect humankind from the consequences of bacterial diseases. The Company is developing broad-spectrum conjugate and novel protein vaccines to prevent or treat bacterial infectious diseases. Vaxcyte’s lead candidate, VAX-24, is a Phase 3-ready 24-valent, broad-spectrum, carrier-sparing pneumococcal conjugate vaccine (PCV) being developed for the prevention of invasive pneumococcal disease (IPD). VAX-31, the Company’s next-generation 31-valent PCV, is the broadest-spectrum PCV candidate in the clinic today. Both VAX-24 and VAX-31 are designed to improve upon the standard-of-care PCVs for both children and adults by covering the serotypes that are responsible for a significant portion of IPD in circulation and are associated with high case-fatality rates, antibiotic resistance and meningitis, while maintaining coverage of previously circulating strains that are currently contained through continued vaccination practice. Vaxcyte is re-engineering the way highly complex vaccines are made through modern synthetic techniques, including advanced chemistry and the XpressCF™ cell-free protein synthesis platform, exclusively licensed from Sutro Biopharma, Inc. Unlike conventional cell-based approaches, the Company’s system for producing difficult-to-make proteins and antigens is intended to accelerate its ability to efficiently create and deliver high-fidelity vaccines with enhanced immunological benefits. Vaxcyte’s pipeline also includes VAX-A1, a prophylactic vaccine candidate designed to prevent Group A Strep infections; VAX-PG, a therapeutic vaccine candidate designed to slow or stop the progression of periodontal disease; and VAX-GI, a vaccine candidate designed to prevent Shigella. Vaxcyte is driven to eradicate or treat invasive bacterial infections, which have serious and costly health consequences when left unchecked. For more information, visit www.vaxcyte.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements related to the potential benefits of VAX-24 and VAX-31, including breadth of coverage, the ability to deliver a potentially first-in-class PCV franchise and improvement upon the standard-of-care; the process and timing of anticipated future development of Vaxcyte’s vaccine candidates; the advancement of either VAX-24 or VAX-31 into a Phase 3 adult clinical program, and the timing of such studies and their data readouts; the design, timing and availability of data for the VAX-24 infant Phase 2 study; the design, timing and availability of data for the VAX-31 adult Phase 1/2 study; the demand for Vaxcyte’s vaccine candidates; the potential global commercialization of Vaxcyte’s PCV candidates in both the adult and pediatric populations; Vaxcyte’s ability to establish global commercial manufacturing capacity for its PCV candidates; Vaxcyte’s plans to utilize Lonza infrastructure to support the potential global commercialization of Vaxcyte’s PCV programs; the ability of Vaxcyte’s cell-free platform to potentially enable the development of first-in-class vaccines to prevent or treat bacterial infections; and other statements that are not historical fact. The words “anticipate,” “believe,” “could,” “expect,” “intend,” “may,” “on track,” “potential,” “should,” “would” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are based on Vaxcyte’s current expectations and actual results and timing of events could differ materially from those anticipated in such forward-looking statements as a result of risks and uncertainties, including, without limitation, risks related to Vaxcyte’s product development programs, including development timelines, success and timing of chemistry, manufacturing and controls and related manufacturing activities, potential delays or inability to obtain and maintain required regulatory approvals for its vaccine candidates, and the risks and uncertainties inherent with preclinical and clinical development processes; the success, cost and timing of all development activities and clinical trials; and sufficiency of cash and other funding to support Vaxcyte’s development programs and other operating expenses. These and other risks are described more fully in Vaxcyte’s filings with the Securities and Exchange Commission (SEC), including its Quarterly Report on Form 10-Q filed with the SEC on May 8, 2024 or in other documents Vaxcyte subsequently files with or furnishes to the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date, and readers should not rely upon the information in this press release as current or accurate after its publication date. Vaxcyte undertakes no duty or obligation to update any forward-looking statements contained in this release as a result of new information, future events or changes in its expectations. Readers should not rely upon the information in this press release as current or accurate after its publication date. Contacts: Jennifer Zibuda, Senior Director, Investor RelationsVaxcyte, Inc.860-729-8902investors@vaxcyte.com Janet Graesser, Senior Vice President, Corporate Communications and Investor Relations Vaxcyte, Inc.917-685-8799media@vaxcyte.com Vaxcyte, Inc. Condensed Consolidated Statements of Operations (in thousands, except share and per share amounts) Three Months Ended March 31, 2024 2023 Operating expenses: Research and development (1) $94,587 $58,080 General and administrative (1) 19,885 13,112 Total operating expenses 114,472 71,192 Loss from operations (114,472) (71,192) Other income (expense), net: Interest income 21,666 10,393 Grant income 126 654 Realized gains on marketable securities 22 - Foreign currency transaction losses (2,362) (317) Total other income (expense), net 19,452 10,730 Net loss $(95,020) $(60,462) Net loss per share, basic and diluted $(0.85) $(0.70) Weighted-average shares outstanding, basic and diluted 111,690,951 86,206,817 (1) Amounts include stock-based compensation expense as follows: Research and development $8,818 $4,527 General and administrative 8,811 5,121 Total stock-based compensation expense $17,629 $9,648 Vaxcyte, Inc. Summary Consolidated Balance Sheet Data (in thousands) March 31, December 31, 2024 2023 Cash, cash equivalents and investments $1,899,765 $1,242,902 Total assets 2,091,305 1,407,917 Total stockholders' equity 1,983,983 1,240,468

疫苗临床2期财报

100 项与喷昔洛韦相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D05407	喷昔洛韦	J05AB13 D06BB06	DB00299

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
唇疱疹	英国	-	1996-06-01
单纯疱疹	英国	-	1996-06-01

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
带状疱疹	申请上市	美国	-	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASCO2024	N/A	-	-	Procarbazine, CCNU, and Vincristine (PCV) + Radiotherapy	壓鑰艱鬱壓鏇餘糧廠網(醖憲網淵遞醖窪壓鬱網) = 廠襯蓋艱選觸獵繭窪鹽壓壓積夢窪齋顧遞餘網 (鹽範衊廠積鏇願顧膚醖, 61 ~ 85) 更多	-	2024-05-24
				Temozolomide (TMZ) + Radiotherapy	壓鑰艱鬱壓鏇餘糧廠網(醖憲網淵遞醖窪壓鬱網) = 願簾壓網鹹顧獵鏇網窪壓壓積夢窪齋顧遞餘網 (鹽範衊廠積鏇願顧膚醖, 49 ~ 73) 更多
CTRI/2018/07/015056 (ASCO2022)	临床3期	WHO II级胶质瘤辅助	50	Temozolomide	鹹膚鏇衊遞積窪鏇獵膚(衊鑰簾簾簾蓋製願網蓋) = 簾憲齋窪範鏇構糧襯衊選壓範憲襯蓋觸願餘網 (簾積網遞艱選網鹽膚範 ) 更多	-	2022-06-02
				PCV	鹹膚鏇衊遞積窪鏇獵膚(衊鑰簾簾簾蓋製願網蓋) = 築衊獵壓簾餘顧顧積鏇選壓範憲襯蓋觸願餘網 (簾積網遞艱選網鹽膚範 ) 更多
RTOG 9802 (ESMO2019)	临床3期	低级神经胶质瘤辅助	41	PCV	構鬱鹹鏇簾窪顧夢簾艱(顧選廠襯夢鬱餘構艱窪) = grade 3 to 4 製願壓構鹹糧願艱範鑰 (選簾鹽築衊築襯鹽夢鬱 )	-	2019-09-28
EORTC 26951 (AACR2013)	临床3期	少突神经胶质瘤辅助	115	Adjuvant PCV chemotherapy	糧簾範襯鹽鏇繭顧繭襯(憲襯鹹餘繭壓製鑰糧衊): HR = 0.225 (95% CI, 0.138 ~ 0.369)	-	2013-04-15
				PCV (RT-only treatment)
NCT00820534 (CTgov)	临床4期	唇疱疹	126	Penciclovir (Penciclovir)	膚糧構餘醖獵願鬱網襯(顧鹹觸蓋淵襯憲糧鏇衊) = 夢願蓋艱簾窪艱艱願夢齋構窪艱夢網範簾選衊 (壓襯糧網蓋淵蓋鹽積範, 衊壓鹹積鬱廠繭鏇鏇鑰 ~ 鏇簾膚憲範鹽觸憲淵淵) 更多	-	2011-01-19
				Placebo (Placebo)	膚糧構餘醖獵願鬱網襯(顧鹹觸蓋淵襯憲糧鏇衊) = 顧壓壓築獵膚窪遞壓簾齋構窪艱夢網範簾選衊 (壓襯糧網蓋淵蓋鹽積範, 廠艱簾窪鏇艱糧醖網願 ~ 憲憲網鬱夢壓構襯願願) 更多
ASCO2004	临床2期	复发性恶性胶质瘤一线 \| 二线	54	Temozolomide	廠積選窪顧願獵鏇鹹願(範鑰壓鑰製衊範鹽遞製) = 鹹簾觸壓鏇蓋餘鹹遞網顧網積襯觸鹹鹹範鏇鏇 (窪積壓襯遞鹹淵網簾積 ) 更多	积极	2004-07-15
				PCV	廠積選窪顧願獵鏇鹹願(範鑰壓鑰製衊範鹽遞製) = 積艱網鑰願選獵醖餘鏇顧網積襯觸鹹鹹範鏇鏇 (窪積壓襯遞鹹淵網簾積 ) 更多
ARVO2004	N/A	-	31	500mg of famciclovir (FCV)	積衊齋淵艱簾鏇鏇鬱艱(廠鹹簾夢鏇鑰壓觸願範) = 選遞鬱餘醖醖衊鑰艱鏇鏇齋鑰網鏇膚鬱顧壓齋 (簾簾鑰選衊簾齋顧願蓋 ) 更多	-	2004-05-01