SARS-CoV-II: A New Hope

Author's preface: Full disclosure. The lead author of the vaccine efficacy paper described below is my current wife and she is a co-author on the manufacturing paper. I did not contribute in any way to either work except perhaps for occasionally acting as a sounding board for my wife's many brilliant ideas. I have said this before and I will say it again here. Not many people get a chance to even meet their heroes. I am so very lucky to have been able to marry mine. Way to go baby. Finally, I am quite proud of the Star Wars reference I managed to work into the title of this article. Very clever. lol!

Two landmark papers by researchers from the University of Louisville's Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, and Kentucky Bioprocessing an Owensboro, KY biotech company almost nobody has ever heard of, were published very recently in a special issue of the Journal Vaccines. Link to journal homepage here. Link to special issue with the two papers is here. (Vaccines is an open access journal and the full text of the two articles can be found here and here) Researcher Mrs. Jennifer DeMarco is lead author on the second paper which demonstrates conclusively the efficacy of a new vaccine (not mRNA based) in mouse models. This vaccine is based on a relatively new technology and possible new vaccine platform. This new platform uses tobacco mosaic virus as the vehicle for antigen delivery, and the tobacco plant itself as a natural manufacturing system to provide a means for producing a stable, effective, vaccine against SARS-CoV-2, and likely its many variants as well.

The researchers involved in these two studies had already previously reported the development of a tobacco mosaic virus virion nanoparticle conjugated to a recombinant SARS-CoV2 antigen containing the receptor-binding domain of the spike glycoprotein fused to a human IgG1 Fc domain that had shown promise in generating immune response in mouse models. However, this work advances that much further and shows the ability of the vaccine to induce a strong neutralizing antibody response in the mouse model and furthermore demonstrates that "immunization protects mice from virus-associated mortality and symptomatic disease." This is really the key finding in my mind and the one that will get all press and attention (and rightly so) but for persons more in tune to what is happening in the field there is a lot more interesting stuff here buried beneath the lede. For instance, the researchers also present (not at all surprising) evidence that "a sufficient pre-existing pool of neutralizing antibodies is required to restrict SARS-CoV-2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease." However, the interesting thing here is that they may have also identified a key protective cytokine in SARS-CoV-2 infection, CXCL-5, suggesting that "disruption of the CXCL-5 and CXCL-1/2 axis may be an important early component of the inflammatory dysregulation that is characteristic of severe cases of COVID-19." This finding, assuming it holds up, could lead to a range of therapeutic options that had not been considered previously.

I am not as familiar with the manufacturing paper but it is just as critical because it shows how the major hurdles associated with the current mRNA vaccines have been sidestepped or completely overcome. This vaccine is stable at room temperature (and higher) for extended periods of time, eliminating the requirement for cold chain handling of vaccine that has so hampered the distribution of the mRNA vaccines, and also probably impacted their efficacy in some persons who were unlucky enough to receive vaccine that had been temperature abused. It can also be quickly modified and new lots produced very quickly to adapt to new variants as they emerge in almost real time.

This really is a feel good story, and win win for all involved, including the state of Kentucky, and its much maligned tobacco industry which still makes up a small chunk of the states current agricultural base, and a large chunk of its proud history. Perhaps tobacco, the main component of cigarettes' and source of the highly addictive nicotine, will finally redeem itself, and shed its reputation as the 'evil' plant responsible for so much sickness and death. Over time it could instead become more known as the platform for a new vaccine technology that has the potential to save many more lives than it ever took. Definitely, executives at the British American Tobacco group (the parent company of Kentucky Bioprocessing) hope that is the case. I give them a ton of credit for their continued support of this work. Vaccine research is a long time horizon, typically low payoff effort that few companies have the stomach to pursue. Maybe they view it as penance for all the damage tobacco has wrought up until now. No matter their motivations, without the backing of a company with very deep pockets like BAT, this vaccine would likely never have seen the light of day.

My sincerest thanks and congratulations to all involved in this important work. While it may not yet be time to pop the champagne corks and celebrate our final victory against SARS-CoV-2 it may be time to begin the procedure of bringing the members of the Nobel prize committee out of their long cryogenic slumber. This work, and the persons involved deserve at least some consideration, particularly if this platform delivers on its potential and becomes the core technology at the heart of many different, new vaccines.

Author's postscript: I have one final special message for Dr. (redacted), my wife's former graduate advisor, who stole her work, patented it, and in the process robbed her of her Ph.D. (I would love to have called you out by name here but fortunately for you Jen forbid it. You know who you are). You will never be half the researcher Jen is and you will never publish anything half as important as this work. How you like them apples...dick.