Flood of COVID-19 vaccines on horizon
Nearly 200 treatments are in clinical trials, a bright spot in fight against virus
Move over, Pfizer and Moderna. You won’t be the only games in town much longer.
COVID-19 has existed for barely more than a year, but 64 vaccines are already in clinical development and another 173 in pre-clinical development worldwide, according to the World Health Organization. Dozens of hopefuls are in clinical trials in the U.S., including several from California researchers.
The two inching closest to the finish line here — from Oxford-astrazeneca and Johnson & Johnson — could win emergency use authorization from the U.S. Food and Drug Administration as soon as this spring, which would instantly increase supply and deliver a much-needed jolt to the nation’s maddeningly sluggish mass
vaccination campaign.
“In science, we often say we’re on the cusp of great things, but now, really, we’re on the cusp of great things,” said Bali Pulendran, professor of microbiology and immunology at Stanford University. “There’s a bubbling cauldron of vaccine ideas out there. It’s unprecedented. When have we ever seen so many candidates developed in such a short amount of time?
“This virus has energized every dimension of vaccinology and we should parlay some of that energy into transforming the field as we know it. We should talk not only about targeting cancer, HIV and influenza, but a whole host of other diseases for which we don’t yet have effective vaccines.”
The breakneck pace of scientific advancement over the past year — fueled by extraordinary cooperation among researchers worldwide, unprecedented financial investment from governments and technology that harnesses the body’s own cellular factories to produce viral proteins, rather than manufacturing them in brick-and-mortar factories — promises an end to a deadly pandemic that has infected nearly 100 million people, killed more than 2 million and paralyzed much of the world.
On the near horizon: a COVID-19 vaccine that can protect after just one shot, rather than two. Vaccines that can be stored in regular refrigerators rather than expensive, ultra-cold freezers. Vaccines that employ a sci-fi smorgasbord of advanced technologies — and even some more traditional approaches — to do their work.
The efficacy of these upand-comers, however, remains to be seen: Will they be as good as Moderna and Pfizer, which deliver a stunning 95% resistance after two shots? It seems clear that many will eclipse the low 50% bar originally set by the FDA for emergency use authorization, but how much better will they be and how will potential recipients react to less-good protection? A more serious issue may be the mutating virus itself: Will it evolve to evade the snares these flotillas have laid to catch it?
Time will tell. Still, more vaccines mean less disease, and less disease means fewer deaths.
The near horizon
Essentially, all vaccines work the same way, by triggering the body’s immune system so it can recognize and fight the invading disease if and when it arrives. How that’s accomplished, though, differs from vaccine to vaccine.
The Moderna and Pfizerbiontech vaccines use a single strand of delicate messenger RNA, wrapped in a fatty package, to deliver instructions to human cells on how to manufacture the virus’s spike protein, in turn triggering the immune response. In contrast, both Johnson & Johnson and Astrazeneca use adenoviruses, of the sortthatcauserunnynoses and common colds, to deliver more rugged, doublestranded bits of coronavirus DNA to the same end.
Johnson & Johnson uses an adenovirus that’s been modified so it can enter cells, but can’t reproduce or cause illness. Some scientists worry that this might be less effective in people who’ve been exposed to similar adenoviruses. Astrazeneca tries to work around this by using a modified adenovirus from chimpanzees, which the human immune system won’t recognize.
The single-dose COVID-19 vaccine being developed by the Janssen Pharmaceutical Cos., the Belgium-based branch of behemoth Johnson & Johnson, is expected to release critical data from late-stage trials in the next week or two, with emergency use authorization coming as soon as March. Vastly simpler than the two-dose regimens, the candidate so far appears highly effective.
Epidemiologist and population health scientist Andrew Noymer at UC Irvine said the single-dose feature is “huge, absolutely huge.” He’s been watching with consternation as people who have received their first Pfizer and Moderna shots struggle to get appointments for the required second doses.
“Two shots is more than twice as complicated as one,” he said.
Storage is vastly simpler as well. Rather than having to be frozen at very low temperatures, Johnson & Johnson’s vaccine can be kept in refrigerators for months. And the company’s sheer size could go a long way toward easing supply strangleholds: Johnson & Johnson has said it hopes to manufacture a billion doses bytheendoftheyear.
Astrazeneca’s version, meanwhile, is more cumbersome, requiring two shots spaced four weeks apart. But storage is similarly simple. And while it already has emergency approval in the United Kingdom — and has been injected into arms for weeks — its path forward in the U.S. is a bit more fraught.
There were issues in Astrazeneca’s late-stage trials that the FDA frowns upon. Researchers mistakenly gave some participants just a half-dose for the first shot and this seemed to provide far more protection than two full doses. The error proved 90% effective at preventing COVID-19, while two full doses were just 62% effective. No one has been able to explain why this would be, leading to some distrust of the results.
The FDA wants more data before considering emergency use authorization, but that could happen as soon as April. The company hopes to produce up to 3 billion doses globally this year.
On the horizon
Arcturus Therapeutics of San Diego is in second phase trials with its RNAbased vaccine. Novavax, based in Maryland, is in late-stage clinical trials as well. Dozens of other vaccine candidates are moving forward in the U.S., China, Russia, Italy, Germany, Japan, the U.K., Israel and several other nations.
Scientists are poring over vital variables to understand how the different vaccines perform: What is the strength of the antibody response after the first vaccination? After the second? Does response wane over time? If a person was already exposed to the coronavirus, does it impact a vaccine’s efficacy, durability or side effects?
At UC Irvine’s Laboratory of Cellular and Molecular Immunology, director Lbachir Benmohamed is pushing the next frontier: a preemptive, “pan-coronavirus” vaccine designed to squash everything from COVID-19 to the common cold. It’s being tested in mice with hopes of starting clinical trials in people this year.
“In the past 20 years, there have been several deadly coronaviruses and there’s no reason to think there won’t be another in the coming years — 2025? 2028? 2030?” Benmohamed said.
At Stanford, Pulendran is working on novel ways to take the guesswork out of vaccine trials altogether.
“It can take years to develop a vaccine and most of that time is spent on testing in humans to see if it induces immunity,” he said. “What if there was some way you could tell very quickly — in smaller phase 1 trials of 50 or 100 people — whether it’s likely to work or not?”
Pulendran’s lab is using immune-monitoring methods to do just that. By taking blood from vaccine trial volunteers and peering deeply at the genetic changes that occur — or don’t occur — in their cells, it’s possible to use computational analysis to predict how they’ll respond over time.
“I feel that sort of thing is going to play an increasingly important role in testing vaccines in humans,” he said.