Vaxart Inc, South San Francisco, CA, USA.
Vaxart Inc, South San Francisco, CA, USA.
Lancet Infect Dis. 2015 Sep;15(9):1041-1048. doi: 10.1016/S1473-3099(15)00266-2.
Most influenza vaccines are manufactured in eggs, and the inactivated virus is purified for injection. For a seasonal influenza product, manufacturing, distribution, and perhaps even vaccine coverage, would be greatly improved with an oral tablet alternative made in cell culture. We aimed to assess the safety and immunogenicity of an oral tablet vaccine against influenza A H1N1 in healthy adults.
At a single site, we did a randomised, double-blind, placebo-controlled trial of a monovalent influenza A H1N1 vaccine to establish the safety and immunogenicity of a recombinant, non-replicating, adenovirus vector expressing haemagglutinin and double-stranded RNA adjuvant delivered orally by tablets. Participants had to have an initial haemagglutination inhibition titre of at most 1/20, be aged between 18 and 49 years, and be in good health. We randomly assigned (1:1) participants to receive either a single oral dose of vaccine or placebo. Randomisation was done by computer-generated assignment, and study drug was distributed with concealed identity to the masked staff by an unmasked pharmacist. Investigative site staff, people directly involved with immunological assays or the assessment of clinical safety, and participants were masked to treatment assignments. Solicited symptoms of reactogenicity were assessed, and all safety assessments were reported through the active phase of the study (day 28). Immunogenicity was assessed by haemagglutination inhibition titres, the percentage of participants that seroconverted, microneutralisation titres, and the number of antibody secreting cells. Descriptive statistics were used for continuous variables and t-tests or Fisher's exact tests were used to compare treatment groups. The study is registered at ClinicalTrials.gov, number NCT01688297.
24 participants were enrolled in the study at WCCT Global between Dec 2, 2013, and April 15, 2014. Adverse events were mild in nature, and occurred with similar frequency in vaccine (four events) and placebo recipients (four events). After immunisation, 11 (92%) of 12 vaccine-treated participants had a four-fold increase in haemagglutination inhibition titres (group geometric mean fold rise of 7·7) and microneutralisation titres (group geometric mean fold rise of 29). No participants in the placebo group had a four-fold increase in haemagglutination inhibition titres (group geometric mean fold rise of 1·1) or microneutralisation titres (group geometric mean fold rise of 1·0). Neutralising antibody responses to influenza were not hindered by pre-existing immunity to the vector.
An oral recombinant adenovirus vaccine to influenza was well tolerated and can elicit neutralising antibody responses to influenza virus in human beings. These data are a step forward in making oral influenza vaccination possible.
Vaxart Inc.
大多数流感疫苗都是在鸡蛋中制造的，灭活病毒被纯化用于注射。对于季节性流感产品，如果使用细胞培养制成口服片剂替代产品，那么其制造、分发，甚至疫苗接种覆盖率都将得到极大改善。我们旨在评估健康成年人中使用甲型 H1N1 流感口服片剂疫苗的安全性和免疫原性。
在一个单一地点，我们进行了一项随机、双盲、安慰剂对照试验，评估了一种单价甲型 H1N1 流感疫苗，以确定表达血凝素和双链 RNA 佐剂的重组、非复制型腺病毒载体的口服片剂疫苗的安全性和免疫原性。参与者的初始血凝抑制滴度必须最高为 1/20，年龄在 18 至 49 岁之间，且健康状况良好。我们将参与者随机分配（1:1）接受单次口服疫苗或安慰剂。随机化通过计算机生成的分配进行，研究药物由未戴口罩的药剂师以隐藏身份分发给戴口罩的工作人员。研究现场工作人员、直接参与免疫测定或临床安全性评估的人员以及参与者均对治疗分配进行了掩蔽。评估了有症状的反应物，并通过研究的主动阶段（第 28 天）报告了所有安全性评估。通过血凝抑制滴度、血清转化率百分比、微量中和滴度和抗体分泌细胞数量评估免疫原性。连续变量采用描述性统计，治疗组间比较采用 t 检验或 Fisher 精确检验。该研究在 ClinicalTrials.gov 注册，编号为 NCT01688297。
2013 年 12 月 2 日至 2014 年 4 月 15 日，WCCT Global 在全球共招募了 24 名参与者。不良事件性质轻微，疫苗组（4 例事件）和安慰剂组（4 例事件）的不良事件发生频率相似。免疫接种后，12 名疫苗治疗者中有 11 名（92%）的血凝抑制滴度增加了四倍（组几何平均倍数增加 7.7），微量中和滴度增加了四倍（组几何平均倍数增加 29）。安慰剂组无参与者的血凝抑制滴度增加四倍（组几何平均倍数增加 1.1）或微量中和滴度增加四倍（组几何平均倍数增加 1.0）。针对流感的中和抗体反应不受对载体预先存在的免疫的阻碍。
一种口服重组腺病毒流感疫苗具有良好的耐受性，可在人体中引发针对流感病毒的中和抗体反应。这些数据是实现口服流感疫苗接种的重要一步。
Vaxart Inc.
