On Tuesday, consumer pharmaceutical giant Johnson & Johnson announced that their vaccine for COVID-19 was entering phase 3 trials. It seems hard to get excited about yet another vaccine at this point, especially when others began their phase 3 trials weeks, or even months, ago. The focus on vaccines, including at Daily Kos, has been primarily on the “fast three”—Moderna, Pfizer/BioNTech, and Astrazeneca/Oxford—all of which involve innovative technology, and all of which are likely just weeks away from leaking out some results from the first wave of phase 3 volunteers. Just about every article, and every politician, discussing the idea of getting a vaccine by year’s end or in early 2021 has concentrated on one of these three.
But there are reasons to think that when it finally comes time for most Americans to visit their local clinic for a COVID-19 vaccine, the answer may be: None of the above. Because there is a second wave of vaccines on the way that have genuine advantages, even if they don’t boast world-changing technology. In the case of the Johnson and Johnson vaccine, while it may seem like their vaccine is late to the ball, they could actually exit phase 3 ahead of their speedier competitors because their vaccine has a secret weapon: Unlike others, it’s just a single shot.
All three of the vaccines that had previously moved to phase 3 in the United States involve the use of two shots. Volunteers receive the two shots about a month apart, and it’s usually not until a few days after the second shot that participants are known to develop levels of antibodies that exceed those generated in a mild-moderate case of COVID-19. Simply moving to a single shot not only means much more convenience for patients who might eventually take the Johnson and Johnson vaccine, it chops a month off the length of their trial and greatly simplifies their testing regime. It also means that when they say the company plans to manufacture 500 million doses, that’s also 500 million patients, not 250 million as it would be with two-dose vaccines. Johnson and Johnson also intends to trial a two-shot version of their vaccine, but this trial is not expected to begin until several weeks from now.
Another advantage that Johnson and Johnson’s vaccine has over earlier competitors is that it’s stable for a period of weeks at room temperature and expected to survive for two years if frozen. That might not make a huge difference in the U.S., but it’s an important feature for a vaccine that is meant to be used around the world.
This isn’t the only vaccine that will be heading to phase 3 in the next few weeks. Right behind Johnson and Johnson are two more pharmaceutical giants. As StatNews reports, Sanofi and Merck may seem like “tortoises” at this point, but that doesn’t mean they won’t end up beating their hare-like competitors in the end. That’s because these companies have extensive experience in conducting trials, in manufacturing, and in distribution. Even if they are not first to market, they may yet end up being the vaccine that many people end up having injected into their arms.
There’s another reason why some of these apparent late-starters may still cross the finish line alongside, or even ahead of, the current leaders: their relative lack of innovation. Right now, the vaccine that looks poised to provide the first phase 3 results is the collaboration between Pfizer and German tech firm BioNTech. But that vaccine, like the close on its heels product from Moderna, depends on the use of messenger RNA. No vaccine of that type has ever been approved for use in humans. In addition, both companies are testing out delivery methods, like Moderna’s unique lipid packaging, that make their vaccines even more novel. Both companies stand to benefit enormously if their trials are successful because they’ll have the keys to a technology that may allow future vaccines to be developed and distributed even more quickly. But for the moment, those new technologies may make regulators—and the companies themselves—highly cautious before moving to public distribution.
The Oxford/AstraZeneca vaccine takes a more traditional approach, packaging key components of the SARS-CoV-2 virus into an adenovirus as a delivery mechanism. However, to avoid possible issues with existing immune response to common adenoviruses, Oxford selected a chimpanzee adenovirus for their vaccine. That choice has raised a few eyebrows; however, it’s another factor that currently has AstraZeneca’s trials on hold in the U.S. A single volunteer back in the U.K. appears to have suffered what may be a very significant side effect from the vaccine, and while the trial is back on track outside the U.S., the FDA still has it on hold here. (Disclosure: I have volunteered to participate in a trial of the Oxford/AstraZeneca vaccine, but have not yet taken part.)
Johnson and Johnson is also packaging their vaccine components into an adenovirus, but their vaccine (known as JNJ-78436735 or Ad26.COV2.S) uses a human adenovirus. A previous human adenovirus-based vaccine developed in conjunction with China’s military failed to generate a strong immune response in early testing, but the Johnson and Johnson results look much stronger. Not only did they generate levels of antibodies that appear to be equivalent to those of the Oxford/AstraZeneca vaccine, they did so after a single dose.
The Chinese military vaccine, Ad5-nCoV, is currently being put through a second phase 3 trial at a higher dose. Since we still don’t know what actually constitutes an effective level of immune response, it may turn out that the Chinese vaccine was good all along, or the level of response seen in all vaccines is too low. That’s one of the things that all these phase 3 trials should reveal.
Like eight other vaccine manufacturers, Johnson & Johnson has signed a pledge to detail the protocols behind their phase 3 trial. They call for a robust trial with 60,000 volunteers in the U.S. and abroad. Recruiting for this many volunteers on three continents will be far from instant, so while the company has announced that they’re ready to begin the trial, it’s unlikely that the ranks of their phase 3 test will be complete before Thanksgiving. The trial will be double-blind, with half of volunteers receiving a placebo. Children will not be included in the trial, with a minimum age set to 18 and “significant representation from those that are over age 60.” The focus will be on trials in nations which, like the United States, have high levels of COVID-19 so that volunteers are subject to a significant risk of infection.
The range of approaches being taken in developing a COVID-19 vaccine makes it more likely that more than one company will emerge with a vaccine that is safe and effective. Which will mean there are approximately 7 billion winners.