Last month, biotech firm Moderna Therapeutics reported very, very early positive results from a Phase 2 trial of their COVID-19 vaccine. This week it was the turn of more established drug maker Pfizer to announce that their vaccine showed similar promise and that they were also heading into Phase 3 studies in the next two weeks. These two vaccines are just two of better than 80 vaccine efforts that have been announced around the world.
Some of the vaccines out there are quite conventional in terms of historic efforts, like an inactivated virus vaccine being trialed by China’s Sinopharm or the Oxford vaccine that leverages a virus normally found in chimpanzees to host fragments of the SARS-CoV-2 virus. The Sinopharm vaccine is finishing up Phase 2 trials, while Oxford began recruiting Phase 3 volunteers back in May and is working to test their vaccine in multiple regions. But in the U. S. it’s Moderna and Pfizer that are leading the chase. Both of them may be successful, but there are definitely reasons for concern.
Moderna has only been around since 2010. It grew out of work by researcher Derrick Rossi who worked out a system for using single-stranded messenger RNA to turn ordinary cells into stem cells, and for several years it was involved in partnerships in a series of trials aimed at finding a treatment for one of several chronic diseases. These diseases, from diabetes to kidney disease to cancer, often offer drug makers the opportunity to create treatments that provide high profit margins over an extended period. However, Moderna’s tests in these areas seem to come up dry—after an announced $350 million of fresh outside investment. So did another, well-publicized effort to use Moderna’s proprietary mRNA-based tech in treatment of rare and orphaned diseases also came up dry. Though the company was hyped as “the next next big thing” in the biotech industry, its early failures and refusal to submit information for peer review resulted in some unflattering comparisons between Moderna and faux testing company Theranos.
Starting in 2014, Moderna shifted resources toward vaccines using mRNA. Early work in this area showed tremendous potential. In an age when the genetic code of viruses could be scanned in weeks or days, mRNA analogs of those viruses could be made just as quickly, inserted into the body those single-strand models of the virus could definitely generate an immune response, but would be unable to replicate like the full virus. Small-scale research continued to show that mRNA was extremely promising, but for a start-up company with two strikes under its belt, this bet also has a serious downside: no mRNA vaccine has ever been approved for human use.
There are reasons for concern. Some researchers have worried that injections of mRNA large enough to generate sufficient immune response might potentially risk generating the kind of overwhelming response—the cytokine storm—that made the 1918 flu so deadly. This type of single-stranded RNA also exists in cells in the midst of replication leading to concerns that “free” mRNA might cause other problems. Like cancer.
So, when Moderna leaped in as one of the first companies to say they were developing a vaccine for COVID-19, there’s a good reason: they needed this. They needed something that so demanded a rapid response; something so big that it would allow them to bypass years, if not decades, of very small-scale tests and long-term studies. MRNA may really be the future of vaccines. The advantages seem to be enormous in terms of rapid production and near guaranteed immune response, and the concerns about safety don’t have much to support them except for … concerns. But there is no doubt that, short of something like COVID-19, Moderna would still be waiting for their first vaccine to be approved in 2030.
Those inclined to be skeptical of the company were not reassured by how Moderna rushed out statements including literally a handful of cases from the very first part of a small-scale trial or how executives from the company cashed in to the tune of selling $89 million of stock after those test results boosted the company’s value on Wall Street.
Moderna’s quick start and rapid movement toward a Phase 3 trial in July seemed to give them a serious lead over any American firm. However, in the last week of June Pfizer and their German partner BioNtech announced that their vaccine was close on Moderna’s heels. Or rather, one of their vaccines, because Pfizer and BioNTech are working on no less than four.
How is it that these other vaccines could be catching up to Moderna’s technique? Well, BioNTech is also a newcomer, only around since 2008, and all four of its COVID-19 vaccines are based on its proprietary tech using … mRNA. The specific ways in which the viral information is being transcribed to mRNA and how the results are administered in vaccines varies between each vaccine. There’s a “nucleoside modified mRNA” vaccine, also known as modRNA. Another vaccine uses a compound found in broccoli and walnuts (and beer) to make uridine-containing-mRNA (uRNA). Another uses self-amplifying mRNA (saRNA) that includes a more complete image of the viral RNA. All of these techniques have been studied in animal trials, and in small human trials with good indications that they are effective.
As Nature reported in 2018, these mRNA techniques promise “a new era in vaccinology” that could see faster, more effective vaccines against both emerging diseases and diseases that have evaded past efforts at vaccines. They could even be effective both in treatment and prevention of several forms of cancer. However, there remains a need to understand how the body reacts to mRNA vaccines, to examine potential long-term effects, and to document both safety and efficacy.
The results from the small amounts of data provided by Pfizer and Moderna look extremely promising. The level of antibody response for both appears to be considerably stronger than that generated by the Oxford Vaccine, and with recent reports that levels of antibodies can fall sharply within two months of infection by COVID-19, those higher levels of response may be important in establishing long-term immunity.
This could be an extremely good thing. If one of the mRNA vaccines proves safe and effective against COVID-19, it really could open that door for rapid improvements in how vaccines are developed and administered going forward. But there are also reasons to keep an eye on safety results.