shot in the arm

The Vaccine Arsenal That Will Win the War on COVID

Shots aimed at the pandemic. Photo: Craig F. Walker/Pool via REUTERS

COVID’s endgame has begun. Vaccinations for the coronavirus got underway in the U.S. on Monday, using a vaccine produced by Pfizer, and approval was given on Friday to another shot by Moderna. Both vaccines appear to be about 95 percent effective at preventing illness from COVID-19. The federal government expects to have enough of both vaccines to protect 150 million Americans by the end of June.

We’ve been remarkably lucky with vaccine development. Back in the spring, experts were cautioning that vaccines typically take decades to gain approval and that the mRNA technology used by Pfizer and Moderna had never before been approved for human use. These vaccines deliver packages of genetic material inside tiny capsules that infiltrate a patient’s cells and cause them to churn out one of the proteins that make up SARS-Cov-2 (the virus that causes COVID-19). The immune system learns to recognize this protein and thereby the entire virus. Virologists expected that the technique would likely only be marginally effective, but the reality has turned out to be dramatically better than that. “Ninety-five percent effective — you couldn’t ask for higher efficacy,” says Rachel Roper, an immunologist at East Carolina University.

But there’s the problem of quantity. Vaccines for 150 million Americans leaves 100 million adults unprotected. For the rest, hope for a jab by the start of summer depends on the next round of vaccines to come through. Here, the road ahead is murkier, as there’s a lot of uncertainty about how effective the next round of candidates will prove to be. Of the four currently undergoing testing as part of Operation Warp Speed, the federal government’s effort to fast-track production of vaccines, two have recently suffered stumbles.

The most dismaying setback has been suffered by Sanofi, the French pharmaceutical giant, which has been developing a vaccine in partnership with GlaxoSmithKline, using a technology called recombinant protein. Instead of slipping genetic material into a patient’s cells so they make viral proteins, the Sanofi vaccine delivers the viral protein itself. It’s a time-tested approach, but on December 11 Sanofi announced that due to poor results in older patients during large-scale clinical trials, it would push back development and no longer expects to seek approval before the fourth quarter of 2021.

Disappointment has also dogged AstraZeneca, the British-Swedish pharma company that is producing what’s called a viral vector vaccine. In this approach, genetic code is inserted into an existing live virus called an adenovirus, which causes a cold in chimpanzees. Having evolved to infect chimps, the adenovirus won’t be able to replicate and cause disease in humans, but it would slip in the genetic material so the human cell can make viral protein to train the immune system to recognize this coronavirus. As a functioning virus it has “all the bells and whistles that turn on the immune response and upset it,” Roper says, which should mean it will spur good protection against COVID-19. The technique has been used successfully in the past, but trials in Britain and Brazil showed significantly lower efficacy than Pfizer and Moderna, preventing only 70 percent of disease. “It’s disappointing and unexpected. I would expect that one to be much better,” says Roper.

On the bright side, even a relatively ineffective vaccine can significantly reduce the number of severe cases that lead to hospitalization and death. “If you had told me a couple of months ago that we would have a vaccine with 70 percent protection, I’d have said, Wow, that’s fantastic,” says Peter Hotez, director of the Texas Children’s Hospital Center for Vaccine Development.

Obviously, anyone would rather take a vaccine that’s 95 percent effective than one that’s 70 percent effective. But with vaccines in short supply over the next few months, the 150 million doses produced by AstraZeneca may be the only option for many if approval is given as expected in late February or early March. “What I’ve been telling people is, don’t wait, because this is a terrible time in this country right now, and you want to do anything you can to get virus-neutralizing antibodies into your system,” says Hotez. “Even if it’s 70 percent protective, it’s still going to be likely enough virus-neutralizing antibodies to reduce the severity of illness.” Vaccines may also reduce the chance that people will become infected and pass along the virus without getting sick themselves, though the data is not yet in to know for sure.

A better alternative might already be available by then, however. Johnson & Johnson is testing a viral vector candidate that uses a different type of adenovirus, and while it hasn’t released any results from ongoing clinical trials yet, things seem to be going well: In early December the company announced that it was reducing the number of participants in its trial from 60,000 to 40,000 because the high prevalence of disease in the public meant a larger proportion would be exposed and the vaccine’s efficacy could be tested. It hopes to gain approval by February.

Unlike all the other Warp Speed vaccines, Johnson & Johnson’s appears to be so effective that the company expects a single dose will be enough — a surprising contrast with the apparently low efficacy of the two-dose AstraZeneca vaccine. “They might have data that convinces them that the level of protection is higher,” Hotez says. Johnson & Johnson is slated to deliver 100 million doses by the end of March.

Bringing up the rear is Novavax, which, like Sanofi, is developing a recombinant protein vaccine and is aiming for approval as early as April or May. Operation Warp Speed has contracted for 100 million doses.

If worse comes to absolute worst with all these second-wave vaccines, the nation would have to wait for Pfizer and Moderna to make more of their  highly effective mRNA vaccines. But Hotez is optimistic that it won’t come to that. “Looking at the data, I’m coming to the impression that the COVID-19 virus is a relatively soft target,” he says. “Pretty much any of these vaccine strategies are going to work.”

If he’s right, then by summer the U.S. should have more than enough vaccines to protect every adult. But that doesn’t mean we’ll be totally out of the woods, because proving that the vaccines are safe and effective for approximately 74 million children is going to take longer. Young people’s immune systems are less robust than those of adults, and giving them unproven pharmaceuticals requires caution. Earlier this month, Moderna announced that it would begin testing its vaccine on kids between the ages of 12 and 17, while Pfizer has been testing children as young as 12 since September.

There’s little hope that the cavalry will arrive in time to salvage much of what’s left of this school year for in-person classes, and even summer camp is looking dubious, but with luck things could be getting back to normal in time for the next academic year. “It would be good to start vaccinating kids in time for the fall school year,” Hotez says. “Whether or not that happens is unclear. But it’s an evolving situation. With each passing month, things will get better as more and more Americans get vaccinated. There will be gradual improvement each passing month, and by the fall I’m hoping that we’ll be in really good shape.”

The Vaccine Arsenal That Will Win the War on COVID