Why you should trust the coronavirus vaccine

Let me start by making one thing clear: at the time of this writing, we don't have a scientifically validated vaccine for COVID-19. But more than 150 vaccines are being developed around the world, and many of them are already in advanced stages of testing.

So we'll have a vaccine soon, likely in a matter of months. And everyone should take it. I know I will.

Today I’m going to try to de-mystify vaccines a bit, in the hope that this might help people feel more comfortable with them.

Before explaining what a vaccine actually is, let me point out that vaccines are probably the single greatest medical advance in the history of human civilization. Vaccines have saved hundreds of millions of lives: prior to vaccines, people lived in fear of diseases like smallpox, which killed 300 million people in the 20th century alone. Thanks to the vaccine, we eradicated smallpox from the entire world in 1980. Polio is another dreaded disease that killed or permanently injured millions, until the 1950s, when Hilary Koprowski, Jonas Salk, and Alfred Sabin invented vaccines that protected against it. Today, no one in the U.S. or Europe worries about polio, and it too has nearly been eradicated worldwide.

What exactly is a vaccine? It’s a pretty simple concept. Our immune system has the remarkable ability to “remember” pathogens that we’ve been exposed to. So once you’ve been infected with some viruses or bacteria, you acquire immunity to those diseases that may last the rest of your life. A vaccine is basically a way to teach the immune system to recognize a pathogen without actually making you sick.

The simplest way to do this (conceptually) is to take a batch of viruses or bacteria, kill them so they’re harmless, and then just inject them into a person. The immune system then “sees” the proteins in the dead pathogens (because the proteins are still floating around), and it learns all it needs to know from these. Later on, if a live virus infects that person, her immune system will say “aha, I know you!” and will quickly surround and destroy the invaders.

Simple as it sounds, there are many complications with this process. One is that it’s often very hard to isolate and grow enough of the virus (or bacteria) for large-scale production. The viruses then need to be isolated, killed, and purified, which can be complicated and costly. For COVID-19, though, any cost is worth it.

Another, much newer way to make vaccines uses modern molecular technology to make RNA. There’s no need to isolate or grow the virus at all! This is how Moderna’s new mRNA vaccine works (see their whitepaper here).

The mRNA vaccine relies on the fact that we already know which protein in the SARS-CoV-2 virus is the most important one. It’s called the spike protein, so I’ll just call it Spike. Spike is what attaches to human cells and lets the virus infect them. We also know the sequence of the Spike gene: the sequence of the entire SARS-CoV-2 virus was released in early January, and we’ve now sequenced thousands of these viruses.

An mRNA vaccine simply uses the RNA itself, rather than dead viruses. Today we can synthesize RNA in large quantities, so if you take some of this RNA and inject it into a person, what happens? Well, our own cells will translate this RNA to produce the Spike protein. All by itself, the protein cannot possibly cause an infection. It’s analogous to having a motor without a car: you can’t go anywhere without the whole package.

But here’s the good part: our immune system will recognize Spike anyway, even without the virus, and it will remember this invader. So the RNA vaccine is, in theory at least, even safer than traditional vaccines, because live pathogens are never used in the production process. (Before the anti-vaxxers jump on me here, let me emphasize that traditional vaccines are incredibly safe.)

This is just one example: there are 23 vaccines already in human trials, and over 150 in development, using mRNA, proteins, and other approaches.

There are other ingredients in vaccines too: preservatives and adjuvants. Anti-vaxxers like to read vaccine ingredients and then claim that all sorts of harmful stuff is in there, but their claims are mostly just gross ignorance. Preservatives are there to prevent the growth of things like bacteria, so they make vaccines safer. And adjuvants like aluminum salts (the most common adjuvant) are ingredients that enhance the effectiveness of vaccines, meaning you can use a lower dose. Aluminum salts have a very long safety record.

So why don’t people trust vaccines? Largely because the anti-vaccine movement has spent years spreading misinformation and fear, and it is already pronouncing strong opposition to any coronavirus vaccine, regardless of the evidence. The New York Times reported this week that mistrust of future coronavirus vaccines could imperil public health, especially in the United States. Polls have shown that large proportions of Americans say they won't take a vaccine even when it's available, which is, frankly, kind of crazy. (It didn’t help when tennis player Novak Djokovic expressed doubts about whether he’d be willing to take any future coronavirus vaccine.) Last month, NIH’s Anthony Fauci said that the “general anti-science, anti-authority, anti-vaccine feeling” in the U.S. may seriously undermine the effectiveness of any future vaccine. Of course, this could change once we really do have a vaccine, and we should all hope it does. But the anti-vaxxers never let up.

It also doesn't help build trust when the Trump administration calls their vaccine program "Operation Warp Speed." This might have sounded exciting to some sci-fi fans in the White House, but to many people it sounds more like a devil-may-care approach that emphasizes speed over safety. 

So how do we establish trust in the new vaccines, which are probably coming just a few months from now? One way to reassure people is to publish all the numbers from the vaccine trials. A just-published study in NEJM on the Moderna vaccine (the RNA vaccine) provides exactly these numbers, and they look very good in terms of both safety and effectiveness. 

In that study, all 45 participants had a robust antibody response–a stronger response, in fact, than in many people who’d been infected with the virus itself. There were some side effects, including fever and chills, but all were graded as mild or moderate. The scientists looked at 3 different dosage levels, and the side effects were greatest in the highest dose–but the antibody response was perfectly adequate in the lower dosage levels. So the next phase of testing, already under way, is using the lower dosages.

This was a phase 1 study, but it's very encouraging. If these results hold up in a large group–a question that is being tested now, in a phase 3 study–we'll have a working vaccine. 

And if you want to know more about this trial, you can read about it at the public NIH site, ClinicalTrials.gov.

Many if not all of the vaccines being developed in Europe and the U.S. are going through the same kind of scrutiny, and we’ll be able to see the results of those tests too. This is how we generate trust in the results: share them openly. I’m very re-assured by what I’ve seen so far.

The bottom line: vaccines work, and our methods for testing them are rigorous and thorough. With a little luck, the world will have multiple COVID-19 vaccines by the end of 2020. Once we have enough people vaccinated, our long nightmare with the coronavirus pandemic will come to an end.

It's not okay to open universities without universal coronavirus testing

Paper strip COVID-19 test developed at MIT
and the Broad Institute

Over the past week, many universities, including my own Johns Hopkins University, announced plans for re-opening this fall. As expected, almost all of them will re-open.

Most of the plans for re-opening are entirely predictable, involving lots of social distancing rules, but in some cases they appear to reflect a mindset that seems more driven by fear of legal liability then genuine concern for everyone's health. If they really care, universities should offer testing to everyone on campus–students, faculty, and staff–and they should make the tests frequent and mandatory. So far, most are not doing this, with exceptions including Cornell University, Yale University, MIT, Dartmouth, and a few others. (Many schools, including Hopkins, haven’t announced a testing plan but yet implement one. Duke and Penn have announced that students will at least be tested initially upon their return.)

It's not really that hard, and it's not that expensive, to offer testing to all students. Let me explain.

Most universities (I've read a dozen or more re-opening plans, but I'll go out on a limb and say "most") plan to open with a mixture of in-person and online classes. In-person classes will be smaller, with students spaced apart in large rooms, and masks required. Larger lectures will be offered online, much as we did this past spring. Universities are also offering students the opportunity to opt out and take a temporary leave of absence if they're not comfortable returning.

Universities know that most students will opt to return. After all, what else can they do? In a normal world, students could take time off to travel, or pursue an internship, or study elsewhere; but in our COVID-infected world right now, there's simply nowhere to go.

So the students will return, and universities will require them to agree to practice social distancing, wear masks, blah blah blah. The students will agree to all these restrictions, and then they will behave like college students everywhere.

In other words, students will get together without masks, party late into the night, and generally share whatever infections any of them have. Luckily for students, the 18-24 year-old age group has very low risk of serious illness from COVID-19. Most of them will recover quickly.

The same is not true for faculty, staff, and the communities around our universities. Many of us (myself included) are far more vulnerable to serious complications if we get infected, and students will unintentionally be vectors for spreading the virus. Without testing in place so that we know who's infected, this is highly likely to happen.

We could greatly reduce the risk of viral transmission if we had universal testing of everyone on campus. This would have to be followed by contact tracing, which we can do with a smartphone app, and isolation of infected individuals. There are now several ways to offer coronavirus testing, and perhaps the most promising is a simple, saliva-based test that only costs a few dollars.

These new tests are based on very elegant CRISPR technology designs; one was described publicly by scientists from MIT, the McGovern Institute, and the Broad Institute in early May (with a preliminary version in February), and another was described publicly by scientists from UC San Francisco and Mammoth Biosciences in mid-February. At least 3 companies–E25Bio, Mammoth Biosciences, and Sherlock Biosciences–are now gearing up to manufacturer these tests, and the cost will be just one to five dollars.

The new paper-strip test couldn't be much simpler: you simply spit into a tube, and then place a specially-treated paper strip into the saliva. (Several other variants on this process are in development.) After some simple processing using inexpensive, widely available equipment, the strip then changes color if the coronavirus is present. The whole process takes under an hour

An alternative to the paper strips is a home-grown virus detection process using modern DNA and RNA sequencing technology. Most major universities (including my own) have this expertise on campus. Working with colleagues at Hopkins, we estimated that we could "roll our own" large-scale testing technology for about $10 per test, with 12-hour turnaround time, and that we could test everyone at least once a week. Not as good as the paper strips, but far better than doing nothing.

Meanwhile, the only FDA-approved tests, based on RT-PCR technology, use nasal swabs, which are far more invasive and difficult to use (you have to stick those swaps deep into the nasal cavity), and cost $50-$100 per test. Either of these reasons suffice to make nasal swab testing impractical as a universal testing method. 

I've already heard objections to these newer tests. The most common refrains are (1) they sometimes have false negatives, meaning that an infection is not detected, and (2) they're not FDA approved. To both of these I have the same response: so what? Is it better to bring back thousands of students, to mix and mingle with hundreds (or thousands) of faculty and staff, and not provide any testing at all? No.

Without a cheap, FDA-approved test, universities have an excuse to take the easy way out: bring everyone back, make them promise to socially distance, and don't offer any testing. Under this scheme, we won't have any way to know who's infected. Many professors and university employees have expressed alarm, and some have signed petitions asking for the right to teach remotely

I agree that universities should re-open this fall–indeed, I think it's imperative to do so, in order to start bringing the world back to normalcy. But universities can't keep pretending that a set of social distancing rules, combined with a mix of online and in-person classes, is enough. 

Many of us don't care if the coronavirus test is FDA approved, and we know it's not perfect. The tests are already quite good, as peer-reviewed papers have shown, and they'll get better. Universities can offer these tests or others to everyone on campus. Cornell University has announced that it will do so, as have Yale, MIT, and Dartmouth. I hope every other college and university, including my own, will do the same.