key: cord-308848-chvvtr0d
authors: Fidel, Paul L.; Noverr, Mairi C.
title: Reply to Özdemir, “Measles-Mumps-Rubella Vaccine and COVID-19 Relationship”
date: 2020-09-22
journal: mBio
DOI: 10.1128/mbio.02465-20
sha: 
doc_id: 308848
cord_uid: chvvtr0d

nan

The question as to whether there may be a cumulative effect of live attenuated vaccines for the nonspecific beneficial immune effects is interesting. While the current clinical trials are not investigating this issue directly, we have focused on the MMR vaccine as it is widely available and has the potential for any or all of the three components to induce the MDSCs. However, based on our data in the animal model of fungal/bacterial sepsis, very strong long-lasting protection is afforded from one administration of the attenuated fungal isolate (7) . Hence, cumulative effects may not be important with the exception of extending the time for optimal protection with timely boosters.

Finally, while it is true that we do not know how long the trained innate immunity persists, the randomized clinical trial of MMR versus placebo in health care workers and the nonhuman primate study that will test MMR or BCG in a model of COVID-19 infection will go far to answer these questions. To date, the trained innate response with BCG suggests the immunity is functional for approximately 1 year based on infant vaccinations (8) . The studies in the animal model of fungal/bacterial sepsis show that the MDSCs are induced quickly (within 7 days of vaccination) and are relatively longlived (up to 120 days) (7, 9) . Data also show that the protection afforded by the trained innate response can be achieved with multiple lethal challenges over time (9) . Since these are mouse studies with relatively short lifespans, we can predict a fairly long half-life for the immune-tolerant trained response in humans. Indeed, the sequelae and hospitalization associated with COVID-19 infection are much reduced in children, teenagers, and even young adults in their early 20s (10, 11) . Children often get the MMR vaccine up to three times by age 11. Thus, it is possible that the nonspecific protective effects provided by the live attenuated vaccines are quite long-lived. Until more is known, however, we are suggesting that the MMR vaccination be given to eligible adults who have not had the vaccination within a year, as an immune preventive against the worst sequelae of any subsequent COVID-19 infection.

Could an unrelated live attenuated vaccine serve as a preventive measure to dampen septic inflammation associated with COVID-19 infection?

Significantly improved COVID-19 outcomes in countries with higher BCG vaccination coverage: a multivariable analysis

Exploratory analysis of immunization records highlights decreased SARS-CoV-2 rates in individuals with recent non-COVID-19 vaccinations

Candida/Staphylococcal polymicrobial intra-abdominal infection: pathogenesis and perspectives for a novel form of trained innate immunity

Homologous protein domains in SARS-CoV-2 and measles, mumps and rubella viruses: preliminary evidence that MMR vaccine might provide protection against COVID-19

MMR vaccine appears to confer strong protection from COVID-19: few deaths from SARS-CoV-2 in highly vaccinated populations

Immune protection against lethal fungal-bacterial intra-abdominal infections

Can a century-old TB vaccine steel the immune system against the new coronavirus

Spectrum of trained innate immunity induced by low-virulence Candida species against lethal polymicrobial intra-abdominal infection

Epidemiology of COVID-19 among children in China

Detection of Covid-19 in children in early