The Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE III) Study - a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 600
- 试验地点
- 2
- 主要终点
- Target rise in HAI titer
研究概览
简要总结
This study will provide novel insight into the effects of repeat influenza vaccination with Flublok and FluMist on the strength and breadth of immune responses to influenza, the mechanisms underlying heterogeneity in vaccine response and vaccine failure, and biological factors that could explain variation in influenza vaccine effectiveness.
详细描述
Annual vaccination remains a key public health approach to reducing the impact of influenza virus infections. However, numerous trials and observational studies, including our own, have demonstrated that repeated an-nual influenza vaccination can result in attenuated vaccine effectiveness in some years in a phenomenon called "repeat vaccination effects". Gaining insight into the varying efficacy of influenza vaccines across different individuals and populations is crucial for optimizing the use of current vaccines and designing universal ones. However, understanding the changes in vaccine effectiveness and immunogenicity among those receiving repeated vaccinations is challenging, especially in populations where universal vaccination is recommended. Repeated vaccinees differ significantly from both new vaccinees and non-vaccinees, potentially leading to residual con-founding in infection and vaccination histories, making it hard to isolate the effects of the vaccine itself.
The investigators will conduct a randomized trial to explore the effects of repeated vaccination and their immunological foundations in a population with low vaccine coverage and no influenza vaccination recommendation. The study will involve live attenuated influenza vaccines (FluMist, nasal spray) in addition to parenteral influenza vaccines (Flublok, injected) to stimulate different components of the immune system. The trial will involve 600 adults in Hong Kong, divided into four groups. The four groups will receive annual vaccination with Flublok, FluMist, alternating between these two vaccines, or alternating between Flublok and placebo. This structure enables comparisons of humoral, mucosal and cellular vaccine responses after different combinations of vaccines.
The resulting longitudinal data on immune status and influenza-specific responses will allow the investigators to develop predictive models for vaccine and infection responses, including those involving repeat vaccinations. The planned immunological profiling, alongside advanced statistical analysis, will enhance understanding of repeated vaccination's effects on seasonal influenza and inform strategies to anticipate vaccine non-responsiveness and improve vaccination approaches. Stored specimens will also allow future testing of new hypotheses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 22 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 22-50 years at enrolment.
- •A. Participated in the DRIVE I or DRIVE II studies (for DRIVE IIIa). OR B. Did not participate in the DRIVE I or DRIVE II study (for DRIVE IIIb) and has not received influenza vaccination in the prior two years.
- •Capable of providing informed consent.
- •Resident in Hong Kong in the coming 2 years.
排除标准
- •Included in one of the priority groups to receive influenza vaccination in Hong Kong (priority groups include pregnant women, long-stay residents of institutions for persons with disability, persons with chronic medical problems (chronic cardiovascular, lung, metabolic or kidney diseases, obesity (body mass index 30 or above) and chronic neurological condition ), healthcare workers or persons working in poultry, pig farming or pig slaughtering industry).
- •With diagnosed medical conditions related to their immune system.
- •Currently taking medication for any condition that impairs immune system.
- •Individuals who report medical conditions not suitable to receive inactivated influenza vaccines, such as:
- •Severe allergic reaction (e.g., anaphylaxis) after previous dose of any influenza vaccine; or to a vaccine component;
- •Moderate or severe acute illness with or without fever after any previous influenza vaccination; or
- •A history of Guillain-Barré syndrome (GBS) within 6 weeks of previous influenza vaccination.
- •Individuals who report medical conditions not suitable to receive live attenuated vaccines, such as:
- •having asthma;
- •having close contact with severely immunosuppressed persons who require a protected environment; or
- •having immunosuppressive treatment (e.g. high-dose steroid, anti-cancer drugs and radiotherapy).
- •Individuals who report medical conditions not suitable to receive intramuscular injection, such as
- •Bleeding disorders
- •Habitually taking anticoagulants (with the exception of antiplatelets such as aspirin).
- •Individuals who have any medical conditions not suitable to receive inactivated or live attenuated influenza vaccines as determined by a clinician.
研究组 & 干预措施
Arm 2: alternate FluMist and Flublok
Alternating FluMist and Flublok annually
干预措施: Placebo injection (Biological)
Arm 3: alternating Placebo and Flublok
Alternating Placebo and Flublok annually
干预措施: Placebo nasal spray (Biological)
Arm 3: alternating Placebo and Flublok
Alternating Placebo and Flublok annually
干预措施: recombinant hemagglutinin influenza vaccine (Biological)
Arm 2: alternate FluMist and Flublok
Alternating FluMist and Flublok annually
干预措施: Placebo nasal spray (Biological)
Arm 2: alternate FluMist and Flublok
Alternating FluMist and Flublok annually
干预措施: recombinant hemagglutinin influenza vaccine (Biological)
Arm 2: alternate FluMist and Flublok
Alternating FluMist and Flublok annually
干预措施: Live attenuated influenza vaccine (Biological)
Arm 3: alternating Placebo and Flublok
Alternating Placebo and Flublok annually
干预措施: Placebo injection (Biological)
Arm 4: 4 x Flublok
Flublok four times annually
干预措施: Placebo nasal spray (Biological)
Arm 4: 4 x Flublok
Flublok four times annually
干预措施: recombinant hemagglutinin influenza vaccine (Biological)
Arm 1: 4 x FluMist
FluMist four times annually
干预措施: Placebo injection (Biological)
Arm 1: 4 x FluMist
FluMist four times annually
干预措施: Live attenuated influenza vaccine (Biological)
结局指标
主要结局
Target rise in HAI titer
时间窗: 30 days
The difference in humoral antibody titers measured by hemagglutination-inhibition (HAI) assay, evaluated by the proportion of participants who achieve a target rise in antibody titre against each of the vaccine strains at 30 days (the targeted rise in antibody titre is defined as the proportion of participants with a four-fold or greater rise in titer, i.e. either a pre-vaccination HAI titer \<10 and a post-vaccination HAI titre ≥20, or a pre-vaccination HAI titer ≥10 and at least a four-fold rise in post-vaccination HAI antibody titer)
GMT ratio
时间窗: 30 days and 182 days
The difference in humoral antibody titers measured by hemagglutination-inhibition (HAI) assay, evaluated by the geometric mean titer (GMT) ratios between the different groups against each of the vaccine strains at 30 days and 182 days.
Detectable mucosal IgG and IgA
时间窗: 30 days and 182 days
The difference in mucosal antibody titers to the vaccine strains in terms of secretory IgA and IgG measured by ELISA, evaluated by the proportion of participants who show titers above detection threshold.
Fold rise in mucosal IgA and IgG
时间窗: 30 days
The difference in mucosal antibody titers to the vaccine strains in terms of secretory IgA and IgG measured by ELISA, evaluated by the proportion of participants who obtain a ≥4-fold rise in IgA and IgG titers
GMT ratios of mucosal IgG and IgA
时间窗: 30 days and 182 days
The difference in mucosal antibody titers to the vaccine strains in terms of secretory IgA and IgG measured by ELISA, evaluated by the geometric mean titer (GMT) ratios between the different groups against each of the vaccine strains at 30 days and 182 days
次要结局
- Proportion above 40(30 days)
- T cell immunity(7 days and 30 days)
- Adverse events(30 days)
- Infection rate(1 year)