Dean's Seminar Series
On October 14, 2020, Dr. Paul Fidel presented for the School of Medicine Dean's seminar. The title of the presentation was “Live attenuated MMR vaccine as a ‘low risk-high reward' immune preventive against COVID-19-associated sepsis.” The presentation started off with evidence for the dichotomous pathogenesis between SARS-CoV-2 infection (COVID-19) and influenza infections, namely the presence of sepsis uniquely associated with COVID-19. This led to discussion of children being largely unaffected by COVID-19 together with mounting evidence that the use of live attenuated vaccines commonly administered during childhood also provide beneficial non-specific immune effects, including reduced mortality to unrelated infections. He then presented data on how live attenuated vaccine non-specific effects are a result of "trained innate immunity," which occurs when the live vaccine “trains” leukocyte precursors in the bone marrow to function more effectively against broader infectious insults. In support of this, work from his laboratory and that of Dr. Mairi Noverr at Tulane School of Medicine, demonstrated that vaccination with live attenuated fungal strains induce "trained innate" Gr-1+ myeloid-derived suppressor cells (MDSC) that protect against lethal polymicrobial sepsis as a novel form of trained innate immunity termed "trained tolerogenic immunity.”
Recognizing that mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis, they put all the pieces of this puzzle together and hypothesized that vaccination with the live attenuated MMR (measles, mumps, and rubella) vaccine may induce the MDSCs that can reduce/eliminate the severe sepsis in those who acquire COVID-19. Accordingly, they have been awarded funding (Parsemus Foundation and Fast Grants COVID-19 Program) to conduct a formal randomized control clinical trial in healthcare workers and first responders who are at high risk for COVID-19 (ClinicalTrials.gov Identifier: NCT04475081). The clinical trial evaluates MMR vaccine vs placebo for the induction of the trained MSDCs at 14, 30, and 60 days post-vaccination, and monitoring of health outcomes of any enrolled subjects who acquire COVID-19 over the 12-month observation period. They suggest that the MMR vaccine has potential to provide a "low risk - high reward" clinical management of COVID-19 cases while a formal COVID-19 vaccine is developed.
The trial is being conducted in partnership with the NIH-sponsored Louisiana Clinical and Translational Science (LA CaTS) award and the LSUHSC Clinical and Translational Research Center (CTRC). Early results from the trial are encouraging with those vaccinated with MMR showing increases in the monocytic MDSC (M-MDSC) subset (See Table).
Preliminary results from MMR vs placebo clinical trial in HCW
|
Group |
M-MDSCa - baseline (% whole blood) |
M-MDSC post-vaccine - fold increase |
G-MDSCb- baseline (% whole blood) |
G-MDSC post-vaccine - fold increase |
|
MMR (n=3) |
0.12% |
Day 14 - 10.2x Day 30 - 32.4x
|
0.30% |
Day 14 - 0.76x Day 30 - 0.59x |
|
Placebo (n=5) |
0.15% |
Day 30 - 3.97x |
0.38% |
Day 30 - 0.90x |
aM-MDSC - monocytic myeloid-derived suppressor cells
bG-MDSC - granulocytic myeloid-derived suppressor cells
Dr. Fidel further noted that any health care workers at high risk for COVID-19 interested in enrolling in the clinical trial should contact Mary at the CTRC at 504-568-2266 or 504-568-2284.
A recording of the seminar can be found at
https://lsuhsc.zoom.us/rec/share/BqyZhxUAYdwhAWtHcFWpvXWQqChse_aEg_MWZqhEstg4iZb1B4VdPHgkxP-HlUWC.vf3meDw4mqtJiZsl
Note that a passcode is required. The passcode is: 2y&2^NfZ
For information related to upcoming seminars, please visit
https://www.medschool.lsuhsc.edu/deanseminar/