Non-specific Effects of FLU-MMR Vaccines in Adults

NCT05401448 | Completed Early Phase 1

• 1 other identifier: FLUMMR-BRA
• Study Type: interventional
• Target: 638
• Locations: 1 country
• Sites: 1

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:

• 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.

Conditions

COVID-19

Keywords

SARS-CoV-2; Heterologous effects of vaccines; Other viral infections

Outcome Measures

Primary Outcomes (3)

• Cumulative incidence of SARS-CoV-2 infection during 1 year follow up

  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

  3 months after inclusion

• Cumulative incidence of SARS-CoV-2 infection

  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

  6 months after inclusion

• Cumulative incidence of SARS-CoV-2 infection

  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

  12 months after inclusion

Secondary Outcomes (3)

• 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

Study Arms (3)

Placebo

PLACEBO COMPARATOR

sterile 0.9% NaCl

Other: Placebo

Influenza

EXPERIMENTAL

Influenza (tetravalent vaccine)

Biological: Influenza

MMR

EXPERIMENTAL

measles, mumps, and rubella vaccine

Biological: MMR vaccines

Interventions

Influenza BIOLOGICAL

Influenza: 0.5 ml of reconstituted Influenza vaccine will be administered intramuscularly in the left upper arm as recommended by the manufacturer.

Influenza

MMR vaccines BIOLOGICAL

MMR: 0.5 ml of reconstituted MMR vaccine will be administered intramuscularly in the left upper arm as recommended by the manufacturer.

MMR

Placebo OTHER

Placebo: 0.5 ml of 0.9% NaCl will be administered intradermally in the left upper arm.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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-19.
• Vaccination in the last 4 weeks against SARS-CoV-2.
• 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.)

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Faculdade da Polícia Militar, Goiânia, GO - Brazil: collaborator

Study Sites (1)

Faculdade da Polícia Militar

Goiânia, Goiás, Brazil

Location

MeSH Terms

Conditions

COVID-19

Interventions

Influenza Vaccines; Measles-Mumps-Rubella Vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Vaccines, Combined; Measles Vaccine; Mumps Vaccine; Rubella Vaccine

Study Officials

• Mihai Netea, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2022
• First Posted: June 2, 2022
• Study Start: June 1, 2021
• Primary Completion: December 31, 2021
• Study Completion: August 31, 2022
• Last Updated: October 2, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)