So you finally got your coronavirus vaccine. It took weeks of waiting, maybe a few calls before hitting the jackpot with a drive-through vaccination clinic. Or maybe you're a health care worker who got the shot at work.
Now comes the hard part -- making sure you get that second dose on time. It means another appointment, and keeping a close eye on the calendar. Plus, perhaps, a little bit of anxiety.
Doctors have been warning people that first dose can have a kick to it. And now, people are starting to report that second dose can cause more side-effects than the first dose.
It's not an unexpected finding. Moderna and Pfizer both said in their submissions to the U.S. Food and Drug Administration that there was a noticeable difference in the reactions to the doses when they were testing their vaccines in volunteers.
"Grade 3 solicited local adverse reactions were more frequently reported after Dose 2 than Dose 1," Moderna's statement reads. Grade 3 adverse reactions include swelling, pain, body aches, headache and fever.
But why?
Analogies always help. Imagine you look out the window one night and see someone skulking around. He looks creepy, and you may be a little alarmed, but you don't panic.
"The first time someone sees that peeping Tom, they might be quite creeped out. They might go to the police station and report this person and someone will draw a sketch and that goes to all the police stations," says evolutionary biology professor Michael Worobey of the University of Arizona.
A few weeks later, you hear a noise, look out the window, and see the same face. You are more likely to react strongly this time, knowing you've seen this face before. Your heart pounds, your hands get clammy and your mind races. You may even call 911. And the police will be ready to come grab the guy.
"The next time that person tries to do something, there is likely to be a much bigger response because there are more people who are familiar with that face now," Worobey explains.
The first dose of vaccine is like that first look at the stranger -- the body's immune system takes notice and takes some precautions, but the second time it's even more primed to recognize and respond to that prompt.
This is how vaccines work in general, of course. They're meant to be like a wanted poster, educating the immune system to be on the lookout.
So-called prime-boost vaccines -- those that work better with two or more doses -- draw out this response.
"With the first dose, you are having to generate an immune response from the ground up," Worobey said.
The body produces antibodies, but also starts to generate immune cells called B cells to make targeted antibodies. This takes time -- a process known as maturing.
"You end up with a finely-tuned B-cell population," Worobey said. "Then the second time you give a person the shot, those cells are sitting around like a clone army and can immediately start producing a very big immune response, which is what is happening when people feel like they have been kicked in the teeth."
Thomas Geisbert, a professor and expert in emerging viral threats at the University of Texas Medical Branch, notes that some vaccines build up plenty of response with a single dose. But the prime-boost strategy builds a longer-lasting defense force, he says.
"Your immune system is already jacked up from the first dose," he said. So with a second dose, "You tend to build up a longer and more durable response."
The flu-like symptoms that come with any viral infection are not caused by the virus itself. They are caused by the body's response. The fever and muscle aches come from inflammation, which in turn is a sign that immune cells called T cells are sending out an alarm in the form of signaling chemicals called cytokines.
"You get swelling at the injection site," said Geisbert. "People can have chills or aches and pains, or they are feeling off or feeling tired."
That bodes well for predicting whether the vaccines will provide better protection than natural immunity. "These symptoms mean that your immune system is revving up and the vaccine is actually working," U.S. Centers for Disease Control and Prevention Director Dr. Rochelle Walensky told a White House briefing last month.
The new coronavirus has only been around for about a year, so no one can say yet whether it will be more like measles, which people catch once in a lifetime, or like influenza, which people catch over and over again.
Studies indicate that anyway -- six months, nine months or even longer.
That's not 100 per cent of the population -- immunity varies a lot from one person to another, and a few cases have been documented of people being infected twice with coronavirus. But they seem to be uncommon instances.
These studies also take snapshots of people's immune systems over time and they show that right after infection, two types of antibody spike in number and then crash, while a third type builds up more slowly. And then B cells that have been "trained" to recognize the virus start producing specific antibodies that build up in the blood.
Vaccination may speed up this process -- providing people quicker protection but also perhaps providing a broader level of protection that a natural infection would.
"Because this is all going so fast, the studies and the key data are not there yet," Geisbert said.
