小狗阅读会员会员
有解析的医学SCI阅读工具

扫码登录小狗阅读

阅读SCI医学文献

Efficacy, immunogenicity, and safety of an oral influenza vaccine: a placebo-controlled and active-controlled phase 2 human challenge study.

口服流感疫苗的疗效、免疫原性和安全性: 一项安慰剂对照和主动对照 2 期人类挑战研究。

  • 影响因子:6.53
  • DOI:10.1016/S1473-3099(19)30584-5
  • 作者列表:"Liebowitz D","Gottlieb K","Kolhatkar NS","Garg SJ","Asher JM","Nazareno J","Kim K","McIIwain DR","Tucker SN
  • 发表时间:2020-01-21
Abstract

BACKGROUND:Influenza is an important public health problem and existing vaccines are not completely protective. New vaccines that protect by alternative mechanisms are needed to improve efficacy of influenza vaccines. In 2015, we did a phase 1 trial of an oral influenza vaccine, VXA-A1.1. A favourable safety profile and robust immunogenicity results in that trial supported progression of the vaccine to the current phase 2 trial. The aim of this study was to evaluate efficacy of the vaccine in a human influenza challenge model. METHODS:We did a single-site, placebo-controlled and active-controlled, phase 2 study at WCCT Global, Costa Mesa, CA, USA. Eligible individuals had an initial A/California/H1N1 haemagglutination inhibition titre of less than 20 and were aged 18-49 years and in good health. Individuals were randomly assigned (2:2:1) to receive a single immunisation of either 1011 infectious units of VXA-A1.1 (a monovalent tablet vaccine) orally, a full human dose of quadrivalent inactivated influenza vaccine (IIV) via intramuscular injection, or matched placebo. Randomisation was done by computer-generated assignments with block size of five. An unmasked pharmacist provided the appropriate vaccines and placebos to the administrating nurse. Individuals receiving the treatments, investigators, and staff were all masked to group assignments. 90 days after immunisation, individuals without clinically significant symptoms or signs of influenza, an oral temperature of higher than 37·9°C, a positive result for respiratory viral shedding on a Biofire test, and any investigator-assessed contraindications were challenged intranasally with 0·5 mL wild-type A/CA/like(H1N1)pdm09 influenza virus. The primary outcomes were safety, which was assessed in all immunised participants through 365 days, and influenza-positive illness after viral challenge, which was assessed in individuals that received the viral challenge and the required number of assessments post viral challenge. This trial is registered with ClinicalTrials.gov, number NCT02918006. RESULTS:Between Aug 31, 2016, and Jan 23, 2017, 374 individuals were assessed for eligibility, of whom 179 were randomly assigned to receive either VXA-A1.1 (n=71 [one individual did not provide a diary card, thus the solicited events were assessed in 70 individuals]), IIV (n=72), or placebo (n=36). Between Dec 2, 2016, and April 26, 2017, 143 eligible individuals (58 in the VXA-A1.1 group, 54 in the IIV group, and 31 in the placebo group) were challenged with influenza virus. VXA-A1.1 was well tolerated with no serious or medically significant adverse events. The most prevalent solicited adverse events for each of the treatment groups after immunisation were headache in the VXA-A1.1 (in five [7%] of 70 participants) and placebo (in seven [19%] of 36 participants) groups and tenderness at injection site in the IIV group (in 19 [26%] of 72 participants) Influenza-positive illness after challenge was detected in 17 (29%) of 58 individuals in the VXA-A1.1 group, 19 (35%) of 54 in the IIV group, and 15 (48%) of 31 in the placebo group. INTERPRETATION:Orally administered VXA-A1.1 was well tolerated and generated protective immunity against virus shedding, similar to a licensed intramuscular IIV. These results represent a major step forward in developing a safe and effective oral influenza vaccine. FUNDING:Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, and Biomedical Advanced Research and Development Authority.

摘要

背景: 流感是一个重要的公共卫生问题,现有的疫苗并不能完全起到保护作用。需要通过替代机制保护的新疫苗来提高流感疫苗的效力。在 2015,我们做了一个口服流感疫苗的 1 期试验,VXA-A1.1。有利的安全性特征和稳健的免疫原性导致该试验支持疫苗进展到目前的 2 期试验。本研究的目的是评估疫苗在人类流感挑战模型中的功效。 方法: 我们在美国加利福尼亚州科斯塔梅萨的 WCCT Global 进行了一项单中心、安慰剂对照和主动对照的 2 期研究。合格个体初始 A/California/H1N1 血凝抑制滴度小于 20,年龄 18-49 岁,健康状况良好。个体被随机分配 (2:2:1) 接受单次免疫接种,口服 1011 个感染单位的 VXA-A1.1 (单价片剂疫苗),全剂量的人四价灭活流感疫苗 (IIV) 通过肌肉注射,或匹配的安慰剂。通过计算机生成的分配完成随机化,块大小为 5。一名未蒙面的药剂师向管理护士提供了适当的疫苗和安慰剂。接受治疗的个人、调查人员和工作人员都被蒙蔽到分组分配。免疫接种后 90 天,无临床显著流感症状或体征的个体,口腔温度高于 37 · 9 ℃,生物火灾试验呼吸病毒脱落阳性结果, 任何研究者评估的禁忌症用 0 毫升野生型 A/CA/like (H1N1) pdm09 流感病毒鼻内激发。主要结局是安全性,在所有免疫接种参与者中评估了 365 天,以及病毒激发后的流感阳性疾病, 在接受病毒攻击的个体和病毒攻击后所需的评估次数中进行了评估。该试验在 ClinicalTrials.gov 注册,编号 nct02918006。 结果: 在 2016年8月31日至 2017年1月23日期间,对 374 人进行了资格评估,其中 179 人被随机分配接受 VXA-A1.1 (n = 71 [1 人未提供日记卡, 因此,在 70 例个体]) 、 IIV (n = 72) 或安慰剂 (n = 36) 中评估了请求的事件。从 2016年12月2日到 2017年4月26日,143 名合格个体 (VXA-A1.1 组 58 人,IIV 组 54 人,安慰剂组 31 人) 接受了流感病毒攻击。VXA-A1.1 耐受性良好,无严重或医学上显著的不良事件。免疫接种后每个治疗组最常见的请求不良事件是 VXA-A1.1 中的头痛 (70 例参与者中有 5 例 [7%]) 和安慰剂 (36 例参与者中的 7 例 [19%]) 组和 IIV 组注射部位压痛 (19 例 [26%])72 名参与者中) 在 VXA-A1.1 组 58 人中有 17 人 (29%) 检测到挑战后流感阳性疾病,IIV 组 54 人中有 19 人 (35%), 和安慰剂组 31 例中的 15 例 (48%)。 解释: 口服 VXA-A1.1 耐受性良好,可产生抗病毒脱落的保护性免疫,类似于经许可的肌内注射 IIV。这些结果代表着在开发安全有效的口服流感疫苗方面向前迈出了一大步。 经费: 卫生和公众服务部、准备和反应助理秘书办公室和生物医学高级研究和发展局。

关键词:
阅读人数:9人
下载该文献
小狗阅读

帮助医生、学生、科研工作者解决SCI文献找不到、看不懂、阅读效率低的问题。提供领域精准的SCI文献,通过多角度解析提高文献阅读效率,从而使用户获得有价值研究思路。

相关文献
影响因子:5.31
发表时间:2020-01-19
DOI:10.1093/cid/ciaa050
作者列表:["Baum U","Kulathinal S","Auranen K","Nohynek H"]

METHODS:BACKGROUND:From 2015/16 through 2017/18, injectable, trivalent inactivated influenza vaccines (IIV3) and a nasal spray, tetravalent live-attenuated influenza vaccine (LAIV4) were used in parallel in Finland. To understand how well vaccination with each vaccine type protected children against influenza under real-life conditions, vaccine effectiveness in two-year-olds was estimated for all three seasons. METHODS:Each season, a nationwide register-based cohort study was conducted. The study population comprised 60,088 children in 2015/16, 60,860 children in 2016/17 and 60,345 children in 2017/18. Laboratory-confirmed influenza was the study outcome. Seasonal influenza vaccination with either LAIV4 or IIV3 was the time-dependent exposure of interest. Vaccine effectiveness was defined as 1 minus the hazard ratio comparing vaccinated with unvaccinated children. RESULTS:From 2015/16 through 2017/18, the effectiveness of LAIV4 against influenza of any virus type was estimated at 54.2% (95% confidence interval, 32.2%-69.0%), 20.3% (-12.7% to 43.6%) and 30.5% (10.9%-45.9%); the corresponding effectiveness of IIV3 was 77.2% (48.9%-89.8%), 24.5% (-29.8% to 56.1%) and -20.1% (-61.5% to 10.7%). Neither of the influenza vaccines clearly excelled in protecting children. The LAIV4 effectiveness against type B was greater than against type A and greater than the IIV3 effectiveness against type B. CONCLUSIONS:To understand how influenza vaccines could be improved, vaccine effectiveness must be analyzed by vaccine and virus type. Effectiveness estimates expressing also overall protection levels are needed to guide individual and programmatic decision-making processes. Supported by this analysis, the vaccination program in Finland now recommends LAIV4 and injectable, tetravalent inactivated influenza vaccines replacing IIV3.

翻译标题与摘要 下载文献
影响因子:1.36
发表时间:2020-01-20
DOI:10.1111/1348-0421.12775
作者列表:["Ainai A","van Riet E","Ito R","Ikeda K","Senchi K","Suzuki T","Tamura SI","Asanuma H","Odagiri T","Tashiro M","Kurata T","Multihartina P","Setiawaty V","Andriana Pangesti KN","Hasegawa H"]

METHODS::Intranasally administered influenza vaccines could be more effective than injected vaccines, since intranasal vaccination can induce virus-specific IgA antibodies in the upper respiratory tract, which is the initial site of infection. In the current study, immune responses elicited by an intranasal inactivated H5 influenza vaccine were evaluated in healthy H5 influenza virus-naive individuals. Three doses of intranasal inactivated whole-virion H5 influenza vaccine induced strong neutralizing nasal IgA and serum IgG antibodies. In addition, a mucoadhesive excipient, carboxy-vinyl polymer (CVP), had a notable impact on the induction of nasal IgA antibody responses but not serum IgG antibody responses. The nasal hemagglutinin (HA)-specific IgA antibody responses clearly correlated with mucosal neutralizing antibody responses, indicating that measurement of nasal HA-specific IgA titers could be used as a surrogate for the mucosal antibody response. Furthermore, increased numbers of plasma cells and vaccine antigen-specific helper T (Th) cells in the peripheral blood were observed after vaccination, suggesting that peripheral blood biomarkers may also be used to evaluate the intranasal vaccine-induced immune response. However, peripheral blood immune cell responses correlated with neutralizing antibody titers in serum samples but not in nasal wash samples. Thus, analysis of the peripheral blood immune response could be a surrogate for the systemic immune response to intranasal vaccination but not for the mucosal immune response. The current study suggests the clinical potential of intranasal inactivated vaccines against H5 influenza viruses and highlights the need to develop novel means to evaluate intranasal vaccine-induced mucosal immune responses. This article is protected by copyright. All rights reserved.

影响因子:6.53
发表时间:2020-01-21
DOI:10.1016/S1473-3099(19)30584-5
作者列表:["Liebowitz D","Gottlieb K","Kolhatkar NS","Garg SJ","Asher JM","Nazareno J","Kim K","McIIwain DR","Tucker SN"]

METHODS:BACKGROUND:Influenza is an important public health problem and existing vaccines are not completely protective. New vaccines that protect by alternative mechanisms are needed to improve efficacy of influenza vaccines. In 2015, we did a phase 1 trial of an oral influenza vaccine, VXA-A1.1. A favourable safety profile and robust immunogenicity results in that trial supported progression of the vaccine to the current phase 2 trial. The aim of this study was to evaluate efficacy of the vaccine in a human influenza challenge model. METHODS:We did a single-site, placebo-controlled and active-controlled, phase 2 study at WCCT Global, Costa Mesa, CA, USA. Eligible individuals had an initial A/California/H1N1 haemagglutination inhibition titre of less than 20 and were aged 18-49 years and in good health. Individuals were randomly assigned (2:2:1) to receive a single immunisation of either 1011 infectious units of VXA-A1.1 (a monovalent tablet vaccine) orally, a full human dose of quadrivalent inactivated influenza vaccine (IIV) via intramuscular injection, or matched placebo. Randomisation was done by computer-generated assignments with block size of five. An unmasked pharmacist provided the appropriate vaccines and placebos to the administrating nurse. Individuals receiving the treatments, investigators, and staff were all masked to group assignments. 90 days after immunisation, individuals without clinically significant symptoms or signs of influenza, an oral temperature of higher than 37·9°C, a positive result for respiratory viral shedding on a Biofire test, and any investigator-assessed contraindications were challenged intranasally with 0·5 mL wild-type A/CA/like(H1N1)pdm09 influenza virus. The primary outcomes were safety, which was assessed in all immunised participants through 365 days, and influenza-positive illness after viral challenge, which was assessed in individuals that received the viral challenge and the required number of assessments post viral challenge. This trial is registered with ClinicalTrials.gov, number NCT02918006. RESULTS:Between Aug 31, 2016, and Jan 23, 2017, 374 individuals were assessed for eligibility, of whom 179 were randomly assigned to receive either VXA-A1.1 (n=71 [one individual did not provide a diary card, thus the solicited events were assessed in 70 individuals]), IIV (n=72), or placebo (n=36). Between Dec 2, 2016, and April 26, 2017, 143 eligible individuals (58 in the VXA-A1.1 group, 54 in the IIV group, and 31 in the placebo group) were challenged with influenza virus. VXA-A1.1 was well tolerated with no serious or medically significant adverse events. The most prevalent solicited adverse events for each of the treatment groups after immunisation were headache in the VXA-A1.1 (in five [7%] of 70 participants) and placebo (in seven [19%] of 36 participants) groups and tenderness at injection site in the IIV group (in 19 [26%] of 72 participants) Influenza-positive illness after challenge was detected in 17 (29%) of 58 individuals in the VXA-A1.1 group, 19 (35%) of 54 in the IIV group, and 15 (48%) of 31 in the placebo group. INTERPRETATION:Orally administered VXA-A1.1 was well tolerated and generated protective immunity against virus shedding, similar to a licensed intramuscular IIV. These results represent a major step forward in developing a safe and effective oral influenza vaccine. FUNDING:Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, and Biomedical Advanced Research and Development Authority.

关键词: 暂无
翻译标题与摘要 下载文献
方向

复制标题
发送后即可在该邮箱或我的下载查看该文献
发送
该文献默认存储到我的下载

科研福利

报名咨询

建议反馈
问题标题:
联系方式:
电子邮件:
您的需求: