MMR vaccine may prevent septic inflammation associated with COVID-19 infection

There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing "trained" nonspecific innate immune cells for improved host responses against subsequent infections.

Researchers have found in a new study that administering the MMR (measles, mumps, rubella) vaccine could serve as a preventive measure to dampen septic inflammation associated with COVID-19 infection. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19, say the researchers.

The study has been published in the journal mBio, a journal of the American Society for Microbiology.

"Live attenuated vaccines seemingly have some nonspecific benefits as well as immunity to the target pathogen. A clinical trial with MMR in high-risk populations may provide a low-risk-high-reward preventive measure in saving lives during the COVID-19 pandemic," said Dr. Fidel. "While we are conducting the clinical trials, I don't think it's going to hurt anybody to have an MMR vaccine that would protect against the measles, mumps, and rubella with this potential added benefit of helping against COVID-19."

Mounting evidence demonstrates that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing trained nonspecific innate immune cells for improved host responses against subsequent infections. Live attenuated vaccines induce nonspecific effects representing "trained innate immunity" by training leukocyte (immune system cells) precursors in the bone marrow to function more effectively against broader infectious insults.

In Dr. Noverr's laboratory, in collaboration with Dr. Fidel, vaccination with a live attenuated fungal strain-induced trained innate protection against lethal polymicrobial sepsis. The protection was mediated by long-lived myeloid-derived suppressor cells (MDSCs) previously reported inhibiting septic inflammation and mortality in several experimental models. The researchers say that an MMR vaccine should be able to induce MDSCs that can inhibit or reduce the severe lung inflammation/sepsis associated with COVID-19. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis.

Recent events provide support for the researchers' hypothesis. The milder symptoms seen in the 955 sailors on the U.S.S Roosevelt who tested positive for COVID-19 (only one hospitalization) may have been a consequence of the fact that the MMR vaccinations are given to all U.S. Navy recruits. In addition, epidemiological data suggest a correlation between people in geographical locations who routinely receive the MMR vaccine and reduced COVID-19 death rates. COVID-19 has not had a big impact on children, and the researchers hypothesize that one reason children are protected against viral infections that induce sepsis is their more recent and more frequent exposures to live attenuated vaccines that can also induce the trained suppressive MDSCs that limit inflammation and sepsis.

The researchers propose a clinical trial to test whether the MMR vaccine can protect against COVID-19, but in the meantime, they suggest that all adults, especially health care workers and individuals in nursing homes get the MMR vaccine. "If adults got the MMR as a child they likely still have some level of antibodies against measles, mumps, and rubella, but probably not the myeloid-derived suppressor cells," said Dr. Fidel. "While the MDSCs are long-lived, they are not life-long cells. So, a booster MMR would enhance the antibodies to measles, mumps, and rubella and reinitiate the MDSCs. We would hope that the MDSCs induced by the MMR would have a fairly good life-span to get through the critical time of the pandemic."

Dr. Noverr was recently awarded a "Fast Grant" (part of Emergent Ventures at the Mercatus Center, George Mason University) to test the efficacy of MMR directly in a nonhuman primate model of COVID-19 infection.

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DOI: 10.1128/mBio.00907-20