Biotech company Moderna reported positive Phase 1 COVID-19 vaccine trial results this morning, boosting its stock shares by 25% and drumming up a media cyclone of excitement. What does this actually mean, though? Not as much as you hope.
- What Moderna tested: Moderna provided three strengths of vaccine to 45 participants beginning in March, all of whom remained generally healthy. The first eight participants produced neutralizing antibody levels similar those found in recovering COVID-19 patients, and in a lab, those antibodies prevented coronavirus from replicating. This is good! But it doesn’t mean that the vaccine will work. Efficacy (whether or not the vaccine protects real live humans from infection) will be tested in a Phase II trial. So far we only know that sticking people in the arm with a Moderna vaccine will not harm them, and spurs their bodies to produce antibodies—which are the minimum qualities one wants in a vaccine. Antibodies are not synonymous with real-world immunity.
- A primer in clinical research: Phase 1 trials serve only to demonstrate the safety and dosage on a small number of people. Phase 2 trials prove efficacy on a few hundred people, and reveal side effects. Phase 3 trials reprove efficacy on 300-3,000 people, and monitor them for adverse reactions. Phase 4 trials are mostly held after a medication is released, and tend to track thousands or millions of users, sussing out obscure side effects.
- What’s next? Moderna will soon start a Phase II trial on 600 participants, and in July will begin a Phase III trial. These trials will test efficacy, presumably exposing the vaccinated people to the infection and seeing if they remain immune. Meanwhile, the Phase I and Phase II results of dozens of other vaccines in development will also be reported.
- A bit of context: Over 100 HIV vaccines have been tested over the years, many with successful Phase I trials. To date, there is no functional HIV vaccine. In 2009, media and researchers alike were enraptured by a Thai Phase III HIV vaccine study which showed partial protection—and that protection turned out to wane over time. Which is all to say that many failed vaccines have had successful Phase I trials. (Yes, HIV and coronavirus are very different viruses.)
- What we do not know: Do antibodies even provide long-term immunity? One hopes they do, but no one knows, including the World Health Organization. Reinfection could be possible, perhaps from mutated strains. We also don’t know why Moderna only reported results on eight of their 45 participants. (“At this time, neutralizing antibody data are available only for the first four participants in each of the 25 µg and 100 µg dose level cohorts.”) We reached out to Moderna for more information and will update if we hear back.
Which is all to say that you should get excited when a vaccine shows long-term efficacy. What we’ve mostly established this morning is that Moderna works fast, and people really, really, really want a vaccine.