Non-specific Effects of FLU-MMR Vaccines in Adults

Plain-language 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.

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