Immunogenicity of Alternative Annual Influenza Vaccination Strategies in Older Adults in Hong Kong - a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 1,861
- 试验地点
- 1
- 主要终点
- Difference in antibody titres
研究概览
简要总结
This study allows to evaluate the strength and duration of immune responses between annual receipt of standard inactivated vaccine and alternative potent vaccines, including annual receipt of adjuvanted inactivated vaccine, annual receipt of high-dose inactivated vaccine, annual receipt of recombinant HA vaccine, and the alternate combinations of the former three vaccines over four years, for identifying improved vaccination strategies for influenza vaccination in older adults in a location experiencing a subtropical pattern in influenza activity.
详细描述
Background: The typical vaccination strategy of annual administration with inactivated trivalent influenza vaccine (TIV) or quadrivalent influenza vaccine (QIV) may provide suboptimal protection to older adults in a location with prolonged periods of influenza activity because of the weaker immune response of older adults to vaccination and because of post-vaccination waning in protection over the course of a year. We hypothesize that in a subtropical or tropical location with prolonged circulation of influenza viruses, the higher antibody titers over years achieved after receipt of annual high-dose vaccine, MF59-adjuvanted vaccine or recombinant haemagglutinin (HA) vaccine, or different vaccination strategies of their combinations with or without the standard vaccine, might lead to greater protection than annual receipt of standard vaccines.
Aim: To test the immune profiles over time of older adults following different influenza vaccination strategies.
Design and subjects: Initially a 4-year immunogenicity study with a randomized controlled design among 2200 older adults aged 65-82 years. We will enroll participants who are willing to receive annual influenza vaccination from the general community including community centres and day-care centres. Eligible individuals will be randomly allocated to ten intervention groups (i.e. annual standard QIV, annual MF59-adjuvanted TIV, annual high-dose TIV, annual recombinant-HA QIV, and six combinations of their alternate annual use) consisting of four rounds of vaccination before each winter influenza season and followed up for 4 years. For each round of vaccination, blood samples for immunological tests will be collected before vaccination and 30 and 182 days after vaccination in all participants, and also at 7, 91 and 273 days after vaccination in a subset of 10% of the participants. Acute illnesses among participants will be monitored by active surveillance efforts during influenza seasons. The vaccine formulation in each round of vaccination will be updated for each season according to WHO recommendations.
Study extension: In years 5-8, all participants will receive the recombinant-HA QIV once per year before each winter influenza season, and their receipt of COVID-19 vaccines will also be recorded. Samples will be collected at the same timepoints to monitor immune responses to influenza vaccination and how responses are affected by prior vaccination history.
Main outcome measures: Antibody titers measured by haemagglutination-inhibition assays, which is an established correlate of protection, in addition to other measurements on humoral and cell-mediated immune responses in the ten intervention groups each year.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 82 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult aged 65-82 years attending ECC and EDC who has not received 2017/18 seasonal influenza vaccine and is willing to receive annual influenza vaccination
排除标准
- •Individuals who show signs of dementia (do not pass the Mini-cog test under Appendix 1a: Recruitment Screening Log) or significant cognitive impairment and are not competent to give their consent.
- •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, including egg protein;
- •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 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 influenza vaccines as determined by a clinician.
研究组 & 干预措施
Alternating standard vaccine & adjuvanted vaccine
Alternating once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: MF 59 adjuvanted inactivated influenza vaccine (NH formulation) (Biological)
Standard vaccine
Once-annual administration of standard vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: Standard inactivated influenza vaccine (NH formulation) (Biological)
Alternating standard vaccine & adjuvanted vaccine
Alternating once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: Standard inactivated influenza vaccine (NH formulation) (Biological)
Alternating adjuvanted vaccine & standard vaccine
Alternating once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: Standard inactivated influenza vaccine (NH formulation) (Biological)
Alternating adjuvanted vaccine & standard vaccine
Alternating once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: MF 59 adjuvanted inactivated influenza vaccine (NH formulation) (Biological)
Alternating standard vaccine and high-dose vaccine
Alternating once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: Standard inactivated influenza vaccine (NH formulation) (Biological)
Alternating standard vaccine and high-dose vaccine
Alternating once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: High-dose inactivated influenza vaccine (NH formulation) (Biological)
Alternating high-dose vaccine and standard vaccine
Alternating once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: Standard inactivated influenza vaccine (NH formulation) (Biological)
Alternating high-dose vaccine and standard vaccine
Alternating once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of standard inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: High-dose inactivated influenza vaccine (NH formulation) (Biological)
Alternating adjuvanted vaccine and high-dose vaccine
Alternating once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: MF 59 adjuvanted inactivated influenza vaccine (NH formulation) (Biological)
Alternating adjuvanted vaccine and high-dose vaccine
Alternating once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: High-dose inactivated influenza vaccine (NH formulation) (Biological)
Alternating high-dose vaccine and adjuvanted vaccine
Alternating once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: MF 59 adjuvanted inactivated influenza vaccine (NH formulation) (Biological)
Alternating high-dose vaccine and adjuvanted vaccine
Alternating once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: High-dose inactivated influenza vaccine (NH formulation) (Biological)
High-dose vaccine
Once-annual administration of high-dose inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: High-dose inactivated influenza vaccine (NH formulation) (Biological)
Adjuvanted vaccine
Once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: MF 59 adjuvanted inactivated influenza vaccine (NH formulation) (Biological)
Recombinant vaccine
Once-annual administration of recombinant hemagglutinin inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: Recombinant hemagglutinin inactivated influenza vaccine (NH formulation) (Biological)
Alternating recombinant vaccine and adjuvanted vaccine
Alternating once-annual administration of recombinant hemagglutinin inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: MF 59 adjuvanted inactivated influenza vaccine (NH formulation) (Biological)
Alternating recombinant vaccine and adjuvanted vaccine
Alternating once-annual administration of recombinant hemagglutinin inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter, and once-annual administration of MF59 adjuvanted inactivated influenza vaccine (northern hemisphere formulation) prior to the northern hemisphere winter throughout 4 years study period.
干预措施: Recombinant hemagglutinin inactivated influenza vaccine (NH formulation) (Biological)
结局指标
主要结局
Difference in antibody titres
时间窗: 30 and 182 days after each vaccination
The difference in antibody titres of participants measured by haemagglutination-inhibition (HAI) assay, evaluated by (1) the proportion of participants who achieve a target rise in antibody titre against each of the vaccine strains at 30 days, and (2) the geometric mean titre (GMT) ratios between the two groups against each of the vaccine strains at 30 days and 182 days. (The targeted rise in antibody titre is defined as the percentage of subjects with either a pre-vaccination HAI titre \<10 and a post-vaccination HAI titre ≥40, or a pre-vaccination HAI titre ≥10 and a minimum four-fold rise in post-vaccination HAI antibody titre.)
次要结局
- Seroprotection(30 days after each vaccination)
- PCR confirmed infection(182 days after each vaccination)
- CMI responses(. 7 days after each vaccination)
- Adverse events(30 days after each vaccination)