Study of the Non-specific Effects of Influenza and MMR Vaccine on Infectious Diseases in Goiânia, Goiás, Brazil
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 638
- 试验地点
- 1
- 主要终点
- Cumulative incidence of SARS-CoV-2 infection
研究概览
简要总结
Various observational studies have reported an association between influenza vaccination and lower rates of infection with SARS-Cov-2 and less COVID-19 disease severity have been reported in large epidemiological studies in US, Brazil and Italy. Observational studies from the Netherlands showed also strongly reduced COVID-19 infection rates among influenza-vaccinated healthcare workers, with ORs of 0.61 and 0.49 for the first and second wave of COVID-19, respectively. In addition, in-vitro immunological analyses showed that the quadrivalent inactivated influenza vaccine can induce a trained immunity program against SARS-CoV-2 (2). In-vivo vaccination against influenza was also shown to induce improved interferon responses against SARS-CoV-2, with modulation of hyperinflammatory responses. Trained immunity could be the underlying mechanism for the potential protective effect of influenza vaccine, a mechanism that has also been proven for BCG vaccination, and epidemiological evidence suggests similar non-specific effects of MMR and OPV vaccination. Currently, various clinical trials are being conducted to study the impact of BCG, MMR and OPV vaccination on COVID-19, but prospective clinical data on influenza vaccination are lacking. Although specific COVID-19 vaccines have been developed and are proven effective, there are important reasons for assessing in a controlled randomized trial the effect of influenza and MMR vaccine on COVID19:
- Specific COVID-19 vaccines are still not yet available for all segments of the population, and especially not for the majority of the population in developing countries.
- The emergence of new SARS-CoV-2 variants, especially the P1 variant from Brazil, may very well be associated with reduced response to vaccines. An immunomodulatory protective vaccine that protects in an antigen-independent manner would be of great importance.
- It would also be conceptually important to know whether influenza and the MMR vaccine can induce heterologous protection against another viral infection, in the context of future pandemics.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •To be eligible to participate in this study, the participant must meet the following criteria:
- •Be older than 18 years old. Observation: the elderly is at risk for severe forms of COVID-19, therefore, the evidence in this age group is very relevant. However, they can also be a first priority population to receive a specific vaccine, limiting the time to follow-up on the study. In addition, influenza and MMR vaccines can lead to a lower immune system in the elderly than in young people. Therefore, it is likely that a more rational choice will be to carry out the study in a young population.
排除标准
- •Participants will not be included in the study if they present (reported by the research participants):
- •Known allergy to components of influenza and MMR vaccines or serious adverse events to previous administration.
- •Fever (> 38 degrees Celsius) in the last 24 hours.
- •Pregnancy. Note: pregnancy should be avoided for one month after vaccination.
- •Symptoms of active viral or bacterial infection.
- •Documented diagnosis of COVID-
- •Vaccination in the last 4 weeks against SARS-CoV-
- •Immunocompromised participants. This exclusion category includes: a) infection with the human immunodeficiency virus (HIV-1); b) neutropenic participant with less than 500 neutrophils/mm3; c) participant with organ transplantation; d) participants with bone marrow transplantation; e) participants in chemotherapy treatment; f) participants with primary immunodeficiency; g) participants with severe lymphopenia with less than 400 lymphocytes/mm3; h) treatment with any anti-cytokine medication; i) treatment with oral or intravenous steroids, for example, daily doses of prednisone or equivalent for more than 3 months, or probable use of oral or intravenous steroids within next four weeks.
- •Some type of lymphoma or malignancy in the previous two years.
- •Direct involvement in the design or execution of the study.
- •Absence from work for more than 4 weeks within the next 12 weeks after study admission (vacation, maternity leave, retirement, planned surgery, etc.)
研究组 & 干预措施
Placebo
sterile 0.9% NaCl
干预措施: Placebo (Other)
Influenza
Influenza (tetravalent vaccine)
干预措施: Influenza (Biological)
MMR
measles, mumps, and rubella vaccine
干预措施: MMR vaccines (Biological)
结局指标
主要结局
Cumulative incidence of SARS-CoV-2 infection
时间窗: 12 months after inclusion
COVID-19 will be defined as meeting the following two criteria: 1. signs and symptoms compatible with the disease as judged by the adjudication committee based on the most recent knowledge of COVID-19 2. microbiological or radiological confirmation: meeting any of the following: a. presence of SARS-CoV-2 virus by PCR
Cumulative incidence of SARS-CoV-2 infection during 1 year follow up
时间窗: 3 months after inclusion
COVID-19 will be defined as meeting the following two criteria: 1. signs and symptoms compatible with the disease as judged by the adjudication committee based on the most recent knowledge of COVID-19 2. microbiological or radiological confirmation: meeting any of the following: a. presence of SARS-CoV-2 virus by PCR
次要结局
- Severity of SARS-CoV-2 and the incidence of clinically relevant RTI(3, 6 and 12 months after inclusion)
- Severity of other respiratory tract infections (RTIs)(3, 6 and 12 months after inclusion)
- Incidence and magnitude of plasma/serum antibodies (IgA, M, G) and SARS-Cov-2-specific antibodies at the end of study(3, 6 and 12 months after inclusion)