Stanford virologist Dr. Robert Siegel getting a flu shot. (Photo/Courtesy Siegel)
Stanford virologist Dr. Robert Siegel getting a flu shot. (Photo/Courtesy Siegel)

Stanford virologist: Fix-everything vaccine is wishful thinking

This Q&A is the first part of our four-part Battling Covid series, in which we speak with local Jewish researchers battling the pandemic.

Dr. Robert Siegel is a longtime professor of microbiology at Stanford University who teaches virology and infectious disease. In a recent phone interview with J., he discussed the coronavirus vaccine trials, the importance of a “slow and careful” approach to vaccine development, and how he thinks people need to get realistic about how soon life will be back to normal.

J.: You have described yourself as “pessimistic” about current Covid vaccine trials. Why?

Siegel: Vaccines are some of the greatest inventions in the history of the world. They’ve saved more lives than almost anything else. Smallpox vaccine saved literally hundreds of millions of lives. But the history of vaccine development is rife with examples of problems that have arisen when vaccines weren’t properly tested. There are vaccines that didn’t work, though they had a hell of a lot of promise. There are vaccines with unpredictable side effects, including some side effects that occur long after the vaccine is given. And then there were vaccines that had great promise but actually made the disease worse when people were infected with the target virus. The [current] rapid pace of development is not reassuring when it comes to avoiding problems like this. It’s being slow and careful that’s going to avoid these problems.

But isn’t it a good thing that vaccine research is happening quickly?

Research is proceeding at an unprecedented pace. There are basically 198 different [coronavirus] vaccines that are in development. Forty-four of them are in human clinical trials — nothing like this has ever happened. And 10 of them are in large-scale phase 3 clinical trials.

There’s a larger diversity of types of vaccine than has ever been tested for any kind of virus before. That’s good, because some of them may work better than others. There are many countries involved, and that’s actually a good thing, because that’s another kind of competition. There are vaccines in Russia and China and Britain and France and all over the world. There’s a large amount of money that is being poured into this, and money often produces results.

Because we know that we’re likely to have a vaccine, and we’re going to want pretty large quantities of it, companies have already started to ramp up their manufacturing facilities even before they know if the vaccine works.

Everybody has a vested interest in getting an effective vaccine. It’s really kind of hard to find any issue that everybody agrees on, but everybody pretty much agrees that we want to get rid of this virus.

What are some of your concerns with the current vaccine trials?

These big trials are actually teeny, and that’s really hard to explain and show. What’s not obvious to the public is the number of endpoints they’re actually looking at for each trial.

Hearing that there’s these large-scale trials — 60,000 people in the trial, that’s impressive. But first we cut that number at least in half because half of the people are in the control group. So we’re not talking about 60,000 people, we’re talking about 30,000 people. Next we have to greatly reduce that number, because of the people in that trial, both in the control group and in the vaccine group — most of them will not be directly exposed to the virus, particularly if the trial is carried out over a short period of time. The number of people who actually get a considerable dose of exposure will be very, very small.

Only serious adverse events matter to this trial. The goal here is to prove that the vaccine recipient gets fewer cases of serious illness than the control group. It’s important [to know] that the researchers are not looking for 100 percent efficacy, they’re looking for at least 50 percent efficacy.

So now you might ask, how many people are we actually looking at? In some trials they’re looking at the differences of 10 people. And in some cases as few as three people. So imagine that in the vaccine group there were three people who got serious disease and in the control group there were six people who got serious disease. Then you might conclude that the vaccine was 50 percent efficacious.

If the vaccine is licensed, that little teeny handful of people, say 10 people, have to represent all of humanity. Those 10 people have to represent the old, the young, the well, the sick, the male, the female and every ethnicity. And that’s just absurd. They can’t.

What are some other problems you foresee?

I think cutting corners is going to hurt us in the long run. And I’m skeptical, based on what I know about coronavirus, that a wildly efficacious vaccine is around the corner.

I am very concerned about emergency use authorization [where the FDA allows a vaccine to be used before being licensed], because that’ll make it much more difficult. It’s going to be difficult to ask somebody to be in a control group for another vaccine. Why should I be in a control group when I can get the vaccine that already has emergency use authorization? It actually decreases our ability to find out additional information.

It’s very concerning that researchers are trying to test vaccines over a few months and assume they’re going to [protect people] for a year. You can’t know that. The same logic applies to serious side effects. How could we possibly know if a vaccine is safe if we only test it for a few months? We won’t know [about] any complication that emerges six months later. There’s many different strains of coronavirus, and it’s going to be very difficult to know if the vaccine works in all different strains.

Most trials are not focusing on the groups that are at greatest risk. They’re not focusing on the elderly, people with comorbidities like obesity, diabetics, people living in communal situations, nursing homes, prisons. If you want the vaccine to represent whether it works for all those groups, you have to test those groups as well.

Do you feel that the public understands the situation?

I’m really worried about the narrative that’s coming from the experts. The whole thing is “blah blah blah until we have a vaccine.” We’ll have to wear masks “until we have a vaccine.” We’ll have to do this “until we have a vaccine.” Unless [vaccines] are 100 percent efficacious, you’ll still have to wear a mask.

The best way to think about a vaccine is that the way to stop this virus is to decrease the rate of transmission, and masks help to do that and a vaccine will help to do that. We want to do everything in our power to decrease the rate of transmission, and therefore decrease the prevalence, and when the prevalence goes down everybody’s risk goes down.

What’s likely to be the case is that we’re going to get a moderately effective vaccine that we may have to get fairly frequently.

What would you like to see happen with vaccine trials?

If we have 100,000 or a million doses of a certain vaccine, and it looks promising, then instead of licensing it or even giving it emergency use authorization, let’s let a board decide at that point which trial should move ahead, and continue to test them, up to hundreds of thousands or even a million people. At that point all the vaccine is being given to people who are at risk. It’s still being tested. We want to be really careful what the results of those trials are before we tell everybody we have the solution.

As long as we have more doses of the vaccine, we need to continue to test them, we need to recruit more volunteers. I’ve actually signed up for a trial. I’m eager to participate. But it’s very dangerous to create the narrative that we have the answer to this pandemic.

Maya Mirsky
Maya Mirsky

Maya Mirsky is a J. Staff Writer based in Oakland.