FLUMMR-BRA: Non-specific Effects of FLU-MMR Vaccines in Adults
Study Details
Study Description
Brief Summary
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:
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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.
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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.
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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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo sterile 0.9% NaCl |
Other: Placebo
Placebo: 0.5 ml of 0.9% NaCl will be administered intradermally in the left upper arm.
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| Experimental: Influenza Influenza (tetravalent vaccine) |
Biological: Influenza
Influenza: 0.5 ml of reconstituted Influenza vaccine will be administered intramuscularly in the left upper arm as recommended by the manufacturer.
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| Experimental: MMR measles, mumps, and rubella vaccine |
Biological: MMR vaccines
MMR: 0.5 ml of reconstituted MMR vaccine will be administered intramuscularly in the left upper arm as recommended by the manufacturer.
|
Outcome Measures
Primary Outcome Measures
- Cumulative incidence of SARS-CoV-2 infection during 1 year follow up [3 months after inclusion]
COVID-19 will be defined as meeting the following two criteria: signs and symptoms compatible with the disease as judged by the adjudication committee based on the most recent knowledge of COVID-19 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 [6 months after inclusion]
COVID-19 will be defined as meeting the following two criteria: signs and symptoms compatible with the disease as judged by the adjudication committee based on the most recent knowledge of COVID-19 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 [12 months after inclusion]
COVID-19 will be defined as meeting the following two criteria: signs and symptoms compatible with the disease as judged by the adjudication committee based on the most recent knowledge of COVID-19 microbiological or radiological confirmation: meeting any of the following: a. presence of SARS-CoV-2 virus by PCR
Secondary Outcome Measures
- Severity of SARS-CoV-2 and the incidence of clinically relevant RTI [3, 6 and 12 months after inclusion]
Cumulative incidence of hospitalization for COVID-19; Cumulative incidence of ICU admission for COVID-19; Cumulative incidence of death due to COVID-19; All parameters combined, measured as number of days or number of deaths will be used to report COVID19 severity.
- Severity of other respiratory tract infections (RTIs) [3, 6 and 12 months after inclusion]
Cumulative incidence of hospitalization for other RTIs; Cumulative incidence of hospitalization for all infections; Cumulative incidence of death due to other infections; All parameters combined, measured as number of days or number of deaths will be used to report the severity of the infection. Cumulative incidence of hospitalization for all infections
- 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]
The measurement of the antibodies titers will be used together with the self informed questionnaires in order to confirm the incidence of COVID19 and/or other RTIs.
Eligibility Criteria
Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
Participants will not be included in the study if they present (reported by the research participants):
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Known allergy to components of influenza and MMR vaccines or serious adverse events to previous administration.
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Fever (> 38 degrees Celsius) in the last 24 hours.
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Pregnancy. Note: pregnancy should be avoided for one month after vaccination.
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Symptoms of active viral or bacterial infection.
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Documented diagnosis of COVID-19.
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Vaccination in the last 4 weeks against SARS-CoV-2.
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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.
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Some type of lymphoma or malignancy in the previous two years.
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Direct involvement in the design or execution of the study.
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Absence from work for more than 4 weeks within the next 12 weeks after study admission (vacation, maternity leave, retirement, planned surgery, etc.)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Faculdade da Polícia Militar | Goiânia | Goiás | Brazil |
Sponsors and Collaborators
- Radboud University Medical Center
- Faculdade da Polícia Militar, Goiânia, GO - Brazil
Investigators
- Principal Investigator: Mihai Netea, PhD, Radboud University Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- FLUMMR-BRA