No Body, Anti-Body But You

Until this go-round, the vaccine process was all about growing an inert version of the virus you are trying to prevent, usually in some form of an egg mixture (which takes a lot of time, with repetitious hits and misses), and injecting that into a human body that will develop an immune response that would also work against the live virus if the person is exposed. A long process. Was there a faster possibility? We’ve had some pretty interesting theories based on our recently developed ability to identify signature genetic characteristics of a toxic virus, through a combination of super-microscopic analysis, and then using a computer to build a mirror of the underlying structure.

Based on this information, what genetic virologists have then been able to do is to rewrite the genetic code (e.g., using CRISPR gene editing technology) for the toxic virus, effectively keeping markers that the human immune system can identify, while eliminating the toxic variables… to create a genetically engineered virus surrogate without the ability to harm. We knew that our ability to rewrite genetic codes would change our ability to create vaccines sooner or later, and we were on the verge of being able to roll out a viable and scalable process, when COVID-19 (formally: SARS-CoV-2) hit. As hundreds of thousands, then millions of people were infected, it was clear that if we did not find a cure or a preventative measure relatively quickly, tens of millions of people, maybe even more, would die. A much great number would catch the infection, and many of those would have long-term effects.

With little to lose, and lots of serious work already years in the making, it was time to roll out this new approach to immunization to see if indeed the theories could be put into immediate practice. The US government seeded some of the efforts to develop a viable anti-COVID vaccine (e.g., Moderna), while others (e.g., BionTech-Pfizer) were completely privately funded. Indeed, the first FDA-approved vaccine out of the box, was that totally privately funded vaccine from a joint venture between a German company, where the vaccine was designed by a husband-wife medical research team (BionTech) who had immigrated to Germany from Turkey, but who needed a big pharma to scale the production to levels that they could not achieve. I wonder if the irony that a pair of Muslim immigrants (that married couple) who created that vaccine was lost on anti-Muslim, anti-immigrant Donald Trump? 

BionTech-Pfizer did get a big order from the US government, but even after all the preliminary tests of that vaccine were increasingly positive, and with the clear knowledge that the US government would not have to pay unless the vaccine truly were effective, when given the opportunity to increase the vaccine order size this past summer, the Trump administration, still laboring under the misguided belief that the pandemic was ending on its own, rejected the offer. That excess was quickly snapped up by other countries. Right now, we are getting that vaccine, but not as much as we need. Hopefully, some of the other vaccines in development will come online soon as well.

Both Moderna and the BionTech Pfizer joint venture employ the new technique described above. Let’s define some of the basic terms: “ribonucleic acid [RNA, is] a nucleic acid present in all living cells. Its principal role is to act as a messenger carrying instructions from DNA for controlling the synthesis of proteins, although in some viruses RNA rather than DNA carries the genetic information.” Wikipedia. “Ribosomal RNA (rRNA), molecule in cells that forms part of the protein-synthesizing organelle known as a ribosome and that is exported to the cytoplasm to help translate the information in messenger RNA (mRNA) into protein. The three major types of RNA that occur in cells are rRNA, mRNA, and transfer RNA (tRNA).” Encyclopedia Britannica.  But it is the messenger capacity – mRNA – that attracted the attention of virologists seeking to carry a new code to the human immune cells charged with attacking invading viruses and bacteria. 

So, what are the human immune cells that this reengineered mRNA is trying to reach? “This first [immune] response is called innate immunity. If you think of it like an army, it is your first line of defense. If the virus passes that, that first line has previously coordinated with the second line of defense—the adaptive immunity… The adaptive immunity is a more specific response to this particular invader to try to clear it. B cells generate antibodies, and T cells help B cells make antibodies and can kill viruses themselves. If everything goes well, you will kill the virus and you will develop some immunity to it.” TuftsNow, December 22nd. Essentially, in these two new vaccines, the mRNA is training the B and T cells how to identify and attack a very specific category of invader – the COVID-19 virus. Adaptive immunity. It is still the clinical testing process that takes the most time, since development time is now so much shorter.

So instead of the multiyear effort to develop a traditional vaccine, “An mRNA vaccine, by contrast, can be made by essentially swapping genetic code in the underlying mRNA platform. In January, when researchers at Moderna and the National Institutes of Health first got the genetic code for the new coronavirus, they finished their new vaccine just days later.

“Scientists first tested the underlying concept as long ago as 1990, when studies showed that mice injected with RNA or DNA could produce the proteins that were encoded. But vaccines or other treatments weren’t viable at first; the mRNA degraded quickly after it was injected and could cause an inflammatory response. A later breakthrough modified the technique so it produced more protein and didn’t cause the same negative response. Next, scientists figured out how to make the mRNA last longer by encasing it in tiny bubbles of fat (a ‘lipid nanoparticle’). Researchers eventually began developing mRNA vaccines for Zika, the flu, and other diseases, overcoming other hurdles through that development. Those other vaccines are still in progress, and nothing had made it through final clinical trials until COVID-19.

“In a future pandemic—a scenario that is, unfortunately, likely—scientists could again quickly plug the genetic code of a new virus into the basic mRNA platform. Because mRNA factories now exist, production could also happen much more quickly. ‘Most manufacturing facilities that are built for vaccines are made to produce one specific vaccine—they’re not adaptable,’ says [Jess Atwell, a scientist at the Department of International Health in the Bloomberg School of Public Health]. ‘But with this technology, you could theoretically put any sequence of mRNA inside the lipid nanoparticle. The manufacturing capacity can be switched from a vaccine for one pathogen to a vaccine for another much more easily than traditional vaccine manufacturing facilities.’

“This type of vaccine could also soon be used for the flu; Moderna had a flu vaccine in early clinical trials before the COVID-19 outbreak began. For the seasonal flu vaccine, which has to be reformulated every year, the new type of vaccine could make it more likely that the vaccine works well. ‘That process has to start in February in the Northern Hemisphere in order to have vaccine in September or October, and sometimes the strains that are chosen don’t end up being the predominant one circulating that winter,’ Atwell says. ‘So if there was technology where you could wait longer to make that decision, and still have vaccine in time for the season, that could be really helpful in making sure that there was a good match between the circulating strains and the vaccine.’” Adele Peters writing for the December 23rd FastCompany.com. 

These mRNA factories are now efficiently and commercially able to recode mRNA to defeat a decoded virus’ genetic signature. Wow! But for rare diseases where there is no financial justification for years of expensive research to service a rarified minority of those impaired, the ability to shortcut a messenger, in days, just might save a few million lives. Who knows how far this new medical technology can go?

I’m Peter Dekom, and for those who really want to understand what these new vaccines can do and how they work, I hope I have helped explain why they were developed so fast and why they absolutely cannot infect those inoculated with the actual virus.