by Sanjay Gupta
Speed and versatility are important when it comes to chasing COVID with vaccines in the years ahead. Changes in the spike proteins drive the variant strains, but our vaccines can still meet the challenge. As more mutations accumulate, tweaks to the vaccines will probably be necessary, like editorial tweaks to written copy to make it stronger and tighter. But we can be well prepared for COVID’s iterations with enough disease surveillance and routine sequencing to keep track of the virus’s evolving characteristics. In the meantime, preventing viral transmission through vaccination is essential to contain the virus and foil its natural tendency to refashion itself.
Immunology 101: The Beauty of Bs and Ts
I can’t cover the benefits of vaccines without dishing out some basic biology about your body’s immune system. It will help you complete the picture in your head about why vaccines are so vital.
The human immune system, which is tasked with keeping you healthy in the face of bacterial, viral, fungal, parasitic, and other invaders, has two main components: the innate immune system and the adaptive immune system.14 The innate immune system is the first line of defense. Parts of it include physical barriers like your skin and mucosal membranes, which physically stop invaders from getting in. It also includes certain cells, proteins, and chemicals that do things like create inflammation and destroy invading cells. Whereas the innate immune system is immediate and nonspecific (it tries to stop anything from entering the body), the adaptive immune system is targeted against a specific and previously recognized invader, which takes a bit longer to kick into gear.
The adaptive immune system includes a type of white blood cell, called a B cell, that patrols the body looking for bad guys. Each B cell has a unique antibody that sits on its surface and can bind to a unique antigen (the technical name for the foreign invader) and stop it from entering a host cell. When it finds and binds to a bad guy, the B cell gets activated: It copies itself and churns out antibodies, eventually creating a mega-army of neutralizers for that particular invader.
That’s where antibodies come from that are created by the immune systems of people who have had COVID. Unfortunately, concerns have risen from a few studies that antibodies to this particular coronavirus can fade away pretty quickly, especially in people who have had mild cases of COVID. This has worried many researchers because if the antibody response fades quickly, we don’t know how long a person who has been infected with this virus will stay protected from a new infection. This is also worrisome since we are relying on vaccines to trigger an antibody response to help protect us, and we want that protection to last a long time.
Fortunately, antibodies aren’t the only weapon our adaptive immune system uses to stave off an infection. Enter the T cell. T cells, which come in three varieties, are created by the body after an infection to help with future infections from the same invader. One of those T cells helps the body remember that invader in case it comes knocking again, another hunts down and destroys infected host cells, and a third helps out in other ways.
After you get an mRNA COVID vaccine, cells in your arm muscle pick up those tiny, fatty droplets that contain the mRNA. The cells start producing a spike protein, which makes your body think its muscle cells are infected with the coronavirus.15 Because of this, your body will try to fight off the simulated infection in the cells with its innate immune system. That’s what causes some of the inflammation that people experience—the sore arms, fevers, and/or muscle aches. What happens next is those cells that have replicated the COVID spike protein (RNA) are seized by immune cells that can communicate with the special cells that make antibodies. Through this exchange, antibodies specific for COVID are generated. This process takes place in your adaptive immune system.
In the case of other vaccines made with DNA, the outcome is the same: a delivery of instructions to the immune system to wake up to the COVID virus. The method of delivery, however, is not directly from an mRNA strand. Instead, a modified adenovirus is used. Adenoviruses are common viruses that typically cause colds or flu-like symptoms. Scientists can deactivate these adenoviruses so they act as vehicles for transporting the coronavirus spike protein gene into cells, without the ability to replicate inside those cells (translation: they do not cause infection). After the vaccine goes into a person’s arm, the adenoviruses bump into cells and latch onto proteins on their surface. The cell engulfs the virus in a bubble and pulls it inside. Once inside, the adenovirus breaks away from the bubble and travels to the nucleus where the cell’s DNA is stored. There, the adenovirus inserts its DNA into the nucleus so those spike protein instructions can be read by the cell and copied into an mRNA that leaves the nucleus and begins assembling spike proteins. In turn, the proliferation of spike proteins alerts the immune system and promotes the same production of COVID-specific antibodies and activated B and T cells.
Many of these vaccines, both mRNA and DNA based, require two doses spaced a few weeks apart. People who feel lousy after the second dose for a day or so can thank their immune systems for showing signs that the vaccine is working. The first dose mimics an infection and organizes the troops, albeit weakly. The second shot riles up the troops and tells them this is serious, turbocharging your immunity against the virus to full capacity. People who experience a reaction after the first shot may attribute that to a previous exposure to COVID whether they were aware of it or not. But to be clear: People who have already gone through a natural infection with COVID should still receive the vaccine because it will boost their overall response to a possible future infection. Examples of other vaccines that require multiple doses include the measles-mumps-rubella (MMR) vaccine, vaccines against hepatitis A and hepatitis B, and the shingles vaccine.
As the United States ramped up its rollout of vaccines in spring 2021, I paid a visit to Pfizer’s manufacturing plant in Kalamazoo, Michigan, and met with the president of global supply, Mike McDermott. Millions of doses were being manufactured every week, and they were on track to get to 2 billion doses by the end of the year.16 Their ability to scale up production tenfold has been a remarkable feat of awesome technology combined with improvements and innovations along the way. Although Pfizer could repurpose some of its equipment, most of what I saw did not exist the previous year. Before Pfizer even knew if they had a product that worked and long before clinical trials would start, the company had spent hundreds of millions of dollars—almost $2 billion by the time I was there.
Before Pfizer decided on its final vaccine candidate, it was looking into four options, which meant that McDermott and his team had to be ready to go in any direction. He described the dilemma to me as like trying to plan an amazing dessert but without knowing what you’re supposed to make. So you start buying up all the raw ingredients to make a cake or brownies, but also a pie or ice cream. “Filling up this pantry,” McDermott quipped, “was quite, quite expensive.”
For McDermott and his team, one of the biggest hurdles that had the possibility of slowing things down was the availability of those raw materials and specifically lipids, the fatty substance that safely houses the mRNA until it can get to our cells. Lipid nanoparticles had not yet been used in a large commercial product, making lipid suppliers in high demand all of a sudden. Pfizer worked closely with these suppliers to build more lipid capacity and also began making lipids on-site.
Ultimately, the successful production of so many vaccines came down to a gizmo the size of a quarter. “The heart of this whole machine,” McDermott showed me, “is what’s called an impingement jet mixer,” he said as he twirled it around his fingers. The impingement jet mixer, also known as the tea stirrer, works by simply pumping lipids in one side and mRNA in the other, forcing them together with around 400 pounds of pressure. That’s what creates the lipid nanoparticle that is essentially the vaccine. These aren’t just any lipids; the company had to design the right combination of four different lipids that would not only protect the mRNA on the way to cells but then release the mRNA once it gets there. And while the pro
cess of creating lipid nanoparticles is not new, McDermott said the challenge was scaling up this process. The first time he saw the impingement jet mixer, McDermott thought, You can’t be serious? His confidence was low. He could not fathom pushing billions of doses through the device. But they eventually solved that problem by replicating the quarter-sized mixers and putting technology in place to ensure efficiency. It was McDermott’s moonshot.
“As a kid, my dad worked for NASA,” McDermott told me. “He was lucky enough to be in mission control in Houston when Neil Armstrong stepped on the moon right at that amazing moment. I could never imagine having a moment like that in my life. Right? Like, what’s the odds that something like that would ever happen again?”
When he shipped his first batch of vaccines from the facility on December 13, 2020, McDermott felt the moonshot moment rush over him.
On my tour of the plant, I saw the warehouse, the vaccine production area, and the freezer farm—the place where they store the vaccine at ultracold −80 degrees Celsius (your freezer is about −20 degrees Celsius, or −4 degrees Fahrenheit) while they’re waiting to be tested. All of the purity testing, processing, and paperwork takes about thirty days, and then the vials are ready to ship. Now the race is on to keep production going and develop new variant-specific vaccines as necessary. I remember talking about the newly authorized vaccines on television one evening in December 2020. The anchor just asked me to reflect on the moment, which wasn’t something I had really thought much about. I had been reporting more intently on the trial process, interpreting the data and manufacturing. After a second, I said, “The story of these vaccines will be told for generations to come,” with the same reverence we have spoken of remarkable public health leaps of the past. Even beyond this pandemic, the pace of medical innovation has forever been changed by what happened this year.
It’s like the story of Roger Bannister and the four-minute mile. In 1956, he was the first person in history to break that record, which many believed wasn’t possible for a human to do. Shortly after that, however, someone else ran even faster, and now there are teenagers who can do it. Bannister was amazing for being first, but his legacy is more about showing us what is possible. The same is true of these vaccines.
My hope is that as people learn more about how these vaccines work and came into being, they will be universally embraced for the modern marvels they are rather than feared or, worse, shunned. As a doctor, I am often asked, “What would you do?” in a certain situation. I think it is a fair question because it requires me to put all the pieces of information together—big and small, clinical trial results and anecdotal case reports—and then make a decision. That is what I always do for my own patients and my family as well. As the only doctor in the family, it was my role long before I was ever reporting on television. And after doing all that homework, I elected to receive the vaccine and recommended it to my parents. As soon as my kids’ age group opened up for vaccination, I made sure they got their shots too to protect them and help reduce overall viral spread. As I have often said about childhood vaccines, it’s not just because I love my kids that I vaccinated them. It’s because I love your kids as well.17
Top 10 Myths Debunked18
Myth: The vaccine will make me infertile, increase my risk for cancer and dementia, and who knows what else.
Truth: The COVID vaccine does not affect fertility. The COVID vaccine was falsely linked to infertility because of the syncytin-1 protein I defined earlier that is an important component of the placenta in mammals. It shares similar genetic instructions with part of the spike of the new coronavirus. If the vaccine causes the body to make antibodies against syncytin-1, it was argued, it might also cause the body to attack and reject the protein in the human placenta, making women infertile. The similarities are not remotely close enough to make a match though. It’s like two people with phone numbers that both include the number 5. They share a digit, but you couldn’t dial one number to reach the other person.19 Plus, if the infertility theory were true, we’d see a shift in fertility statistics among the tens of millions of people who’ve been infected or vaccinated. During the Pfizer vaccine trials, twenty-three women volunteers involved in the study became pregnant, and the only one who suffered a pregnancy loss had received not the actual vaccine but a placebo.
Myth: The vaccine will change my DNA.
Truth: Without an understanding of biochemistry, it’s easy to think that injecting genetic material into the body will somehow mix with our DNA and change it. But that is not the case (and if it were, imagine what we’d be able to accomplish!). You are not a GMO after being vaccinated. Nor are these vaccines “gene therapy,” another subject entirely unrelated to COVID. First, the mRNA vaccines act as messengers to cells without ever entering their nucleus. They hand-deliver a recipe for making those spike proteins, and then they are destroyed by the cell (they shoot the messenger). Viral vector vaccines that use DNA (e.g., adenovirus) do go into the cell’s nucleus, but they do not integrate with your own DNA. These vaccines, which have fifty years of history, act like delivery shuttles to serve up the genes for making the same antigen COVID spike protein. Unlike retroviruses such as HIV, wild-type adenoviruses do not carry the enzymatic machinery necessary for integration into the host cell’s DNA. That’s exactly what makes them good vaccine platforms for infectious diseases.
Myth: People who take these new vaccines are guinea pigs. Researchers rushed the development of the COVID vaccine, so its effectiveness and safety cannot be trusted.
Truth: The vaccines were authorized quickly in part because red tape was cut, not corners. As noted, the mRNA vaccines were created with a method that has been in development for decades. The companies could start the vaccine development process early in the pandemic because they were at the ready to deploy this technology. The more traditional vaccines also came into being from decades of experience. The vaccine developers didn’t skip any testing steps, but conducted some of the steps simultaneously to gather, and share, data faster. These vaccine endeavors had plenty of resources, as governments invested in research or paid for vaccines in advance, or both. Social media helped companies find and engage study volunteers, and millions of people have now proven the vaccines’ success. Because COVID is so contagious and widespread, it did not take long to see if the vaccine worked for the participants who were vaccinated.
Myth: I never get flu shots because they give me the flu. Why would I get a COVID vaccine when it will also make me sick, from side effects to the illness itself?
Truth: None of the vaccines for COVID can give you the disease. The spike protein that stimulates your immune system to recognize and fight the virus does not cause infection of any sort. Any side effects from the vaccine are related to the immune system waking up and doing its job. And with regard to flu, you cannot contract influenza from a flu shot. People who feel sick from a flu shot can either blame their own immune system kicking into gear or blame an illness they contracted naturally before the flu shot had enough time to work. Similarly, these COVID vaccines also need time to work. Upon inoculation, you’re not instantly immune to the virus. You reach full vaccination status two weeks after a single-dose vaccine like the J&J one, or two weeks after the second mRNA shot. And you don’t want to miss that second mRNA shot. Although you do have some immunity a couple of weeks after the first jab, slightly over 50 percent, you need the second jab to fill up your immunity cup to the 90 percent–plus level of protection. When people become COVID positive and develop symptoms soon after vaccination, they may have contracted the virus before the vaccine has time to deploy, or fall into the small percentage of people who don’t achieve enough protection. And contrary to other reports, once vaccinated, you do not shed virus because of the vaccine.
Myth: I’ve already had COVID, so why bother with the vaccine? I’m immune naturally. And I have allergies, so…
Truth: It is true that your previous infection has offered you protective antibodies and likely revv
ed up other parts of your immune system as well. Still, there may be a benefit to getting vaccinated because the vaccine appears to offer better protection against the emerging variants and stronger protection overall. While we haven’t seen significant reinfection rates in the United States, other countries with emerging variants such as Brazil have been hit quite hard. Even people with severe allergies, including ones that require them to carry an EpiPen, can safely receive the vaccine and are encouraged to do so under special supervision in a health care setting. For people who have had COVID and go on to experience long-haul symptoms, getting vaccinated appears to significantly diminish or totally eliminate those symptoms in many patients.
Myth: The vaccines contain questionable substances, some of which could be used to monitor or control me—maybe even turn me into a zombie.
Truth: Contrary to misinformation swirling online about what’s in these vaccines, they do not contain any suspicious ingredients or “toxins” as some say. They do not contain any dubious material, such as implants, microchips, or tracking devices. In addition to the main COVID-killing ingredient found in their genetic instructions, they also contain a support staff of fats, salts, and a small amount of sugar. And they were not developed using fetal tissue.
Myth: Once I’m vaccinated, I’m bulletproof and can fully return to normal life.
