Could an Unrelated Live Attenuated Vaccine Serve as a Preventive Measure To Dampen Septic Inflammation Associated with COVID-19 Infection?

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Salient features:

This article focuses on:

  • Rationale
  • Mechanism of action
  • Different clinical trials performed

Detailed summary:

Rationale:

  • To support the use of live attenuated vaccines, such as MMR (measles, mumps, rubella), as a preventive measure against the pathological inflammation and sepsis associated with coronavirus disease 2019 (COVID-19) infection.

Mechanism of action:

  • Live attenuated vaccines induce nonspecific effects representing “trained innate immunity” by “training” leukocyte precursors in the bone marrow to function more effectively against broader infectious insults.
  • Vaccination with a live attenuated fungal strain induces trained innate protection against lethal polymicrobial sepsis.
  • The protection is mediated by long-lived myeloid-derived suppressor cells (MDSCs) previously reported to inhibit septic inflammation and mortality in several experimental models.
  • Induction of the MDSCs can inhibit or reduce the severe lung inflammation/sepsis associated with COVID-19.

Different clinical trials performed:

  • On the basis of data from prior BCG trials in infants, the vaccine-induced trained innate cells remain in the circulation for roughly 1 year.
  • One caveat concerning BCG vaccination is seroconversion, which is the basis for the TB diagnostic test currently used in the United States.
  • Therefore it is proposed that the use of the live attenuated MMR vaccine, which has also been found to be associated with beneficial NSE in human populations.
  • According to the Centers for Disease Control (CDC), there are few contraindications against administration to adults of a live attenuated vaccine such as MMR if the recipient is immunocompetent and not pregnant and has not shown previous allergic responses to vaccination.
  • MMR vaccination is recommended in high-risk adults and people born before 1957 who did not receive the vaccine as a child.
  • Adults who had received the MMR vaccine in childhood likely still possess antibody titers against the targeted viruses but not the shorter-lived trained innate leukocytes.
  • MMR vaccine would provide added protection against measles, mumps, and rubella for older adults.
  • But with the added induction of the trained innate cells, the MMR vaccination could provide protection against the worst sequelae of COVID-19.
  • Epidemiological data suggest a correlation between subjects in geographical locations who routinely receive live attenuated measles-rubella vaccines such as the commonly available MMR vaccine, and reduced COVID-19 death rates.
  • With SARS and MERS, mortality is the result of severe pulmonary inflammation and sepsis induced by the virus resulting in eventual organ failure.
  • So it is hypothesized that one reason that children are protected against viral infections that induce sepsis is their more recent and more frequent exposures to live attenuated vaccines (MMR, rotovirus, smallpox, chickenpox, BCG) that can also induce the trained suppressive MDSCs that limit inflammation and sepsis.
  • As a response to this hypothesis along with the supportive rationale and considerable observational data supporting the hypothesis, a randomized clinical trial to be performed with MMR in New Orleans for high-risk health care workers and first responders has been proposed.

Reference Link: https://mbio.asm.org/content/11/3/e00907-20

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