The DTP vaccine teaches us about how brilliant vaccine technology can be, but also how it can be studied and improved over time.
This time of year, my thoughts turn to the DTP vaccine. Last year I wrote about the apocryphal “Christmas miracle” of 1891, in which the newly discovered diphtheria antitoxin may (or more likely, may not) have been used before it had been approved to save a child’s life.
Still, the moral was that bacteriology, that new 19th-century science, had figured out how one of the deadly microscopic bacteria did its damage, with a poison that could choke off children’s airways, and had invented an antidote, and that was miracle enough.
Soon after that column was published, we began to hear about a new microbial threat making it hard for people to breathe in Wuhan, China, and, well, you know the rest of the story. But now, a year later, I am — no surprise — thinking about vaccines, and how far this technology has come.
When I write about diphtheria, I usually mention that I have never seen it; by the time that I went to medical school and trained in pediatrics, it was already a historical disease in this country. My teachers could remember measles, and some of the older ones had seen polio, but no one in the 1980s in Boston was telling war stories about diphtheria.
Pertussis was different — the “P” in the DTP. Pertussis, better known as whooping cough, was still around, still something to worry about when a baby came in with a particularly bad cough, still something we worried we might miss. Once we heard the whoop, our teachers told us, we would never forget it.
And since the immunity did not last forever, either from childhood vaccines or from actual disease, and there was, at that time, no safe adult booster shot for pertussis, there was no way to protect us; whenever a child did turn out to have the disease, all the doctors and nurses and family members who had been exposed to that child would have to take a course of antibiotics, in case they had also been infected, and many pediatric residents ended up taking those antibiotics two or three times.
But you didn’t always know that you’d been exposed. In fact, I managed to catch pertussis in the line of duty and, without knowing it, to expose lots of babies and children, since I went on working when I was sick (in my own not-very-valid defense, I was just behaving in accordance with the fairly idiotic and highly macho rules of medicine, rules we can hope that the experience of Covid-19 will change forever).
The first thing you should know about the DTP vaccine is that all three of the diseases against which it protected a child — diphtheria, tetanus and pertussis — are bacterial diseases, unlike, for example, polio or smallpox, which are viral diseases. And one reason you may have been reading recently about the triumphs of polio vaccine in the 1950s, or the successful campaign to eradicate smallpox worldwide, is that the biological entities that cause those illnesses are more similar to the coronavirus that causes Covid-19 than any bacterial illness.
Still, the story of the DTP vaccine, and in particular the story of vaccinating against pertussis, has some interesting things to tell us, about how brilliant vaccine technology can be, but also how it can be studied and improved over time, and about trade-offs and controversies.
The first pertussis vaccines were developed and tested in the 1920s and 1930s and were in universal use by the end of the 1940s. And they worked. Dr. James Cherry, a distinguished research professor of pediatrics at David Geffen School of Medicine at the University of California, Los Angeles, and an expert on pertussis who has done extensive research both on the disease and on the vaccines, cites more than 36,000 pertussis deaths from 1926 to 1930 in the United States, most in young infants; from 1970 to 1974, there were 52.
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Life will return to normal only when society as a whole gains enough protection against the coronavirus. Once countries authorize a vaccine, they’ll only be able to vaccinate a few percent of their citizens at most in the first couple months. The unvaccinated majority will still remain vulnerable to getting infected. A growing number of coronavirus vaccines are showing robust protection against becoming sick. But it’s also possible for people to spread the virus without even knowing they’re infected because they experience only mild symptoms or none at all. Scientists don’t yet know if the vaccines also block the transmission of the coronavirus. So for the time being, even vaccinated people will need to wear masks, avoid indoor crowds, and so on. Once enough people get vaccinated, it will become very difficult for the coronavirus to find vulnerable people to infect. Depending on how quickly we as a society achieve that goal, life might start approaching something like normal by the fall 2021.
Yes, but not forever. The two vaccines that will potentially get authorized this month clearly protect people from getting sick with Covid-19. But the clinical trials that delivered these results were not designed to determine whether vaccinated people could still spread the coronavirus without developing symptoms. That remains a possibility. We know that people who are naturally infected by the coronavirus can spread it while they’re not experiencing any cough or other symptoms. Researchers will be intensely studying this question as the vaccines roll out. In the meantime, even vaccinated people will need to think of themselves as possible spreaders.
The Pfizer and BioNTech vaccine is delivered as a shot in the arm, like other typical vaccines. The injection won’t be any different from ones you’ve gotten before. Tens of thousands of people have already received the vaccines, and none of them have reported any serious health problems. But some of them have felt short-lived discomfort, including aches and flu-like symptoms that typically last a day. It’s possible that people may need to plan to take a day off work or school after the second shot. While these experiences aren’t pleasant, they are a good sign: they are the result of your own immune system encountering the vaccine and mounting a potent response that will provide long-lasting immunity.
No. The vaccines from Moderna and Pfizer use a genetic molecule to prime the immune system. That molecule, known as mRNA, is eventually destroyed by the body. The mRNA is packaged in an oily bubble that can fuse to a cell, allowing the molecule to slip in. The cell uses the mRNA to make proteins from the coronavirus, which can stimulate the immune system. At any moment, each of our cells may contain hundreds of thousands of mRNA molecules, which they produce in order to make proteins of their own. Once those proteins are made, our cells then shred the mRNA with special enzymes. The mRNA molecules our cells make can only survive a matter of minutes. The mRNA in vaccines is engineered to withstand the cell's enzymes a bit longer, so that the cells can make extra virus proteins and prompt a stronger immune response. But the mRNA can only last for a few days at most before they are destroyed.
Even so, when I started out in pediatrics, in the 1980s, the DTP was, no question, the shot we least liked giving. Of the shots that we routinely gave, this was the one that kids tended to react to — with fevers, with sore arms, and sometimes, though very rarely, with more serious reactions. “Reactogenic,” we sometimes called it.
The reactions had a lot to do with what went into the vaccine: whole inactivated Bordetella pertussis bacteria. And though bacteria are microscopically small, they are enormous and complex cells compared to viruses, which are just made up of protein and nucleic acid (DNA or RNA). In other words, a whole-cell vaccine contained many different compounds in it that the body might react to — there are more than 3,000 different proteins in the bacterial cell. For diphtheria and tetanus, single “toxoids” were used, inactivated versions of the poisons manufactured by those bacteria, so those components were much less reactogenic.
There were parents who believed that their children had been harmed by the vaccine, and strong sentiment against it in what we would now call the anti-vaccine movement, along with ongoing medical controversy over which problems had been caused by the vaccine and which were coincidences of timing in a vaccine given at 2, 4 and 6 months of age, and then again at around a year and a half.
Since 1999, children in the United States have been vaccinated with DTaP, rather than DTP, with the “a” standing for “acellular.” No more whole cells; these vaccine developers used specific proteins to which the body would manufacture immunity. DTaP shots are significantly less “reactogenic.”
They also tend to be less effective in provoking a long-lasting effective immune response; in a 2019 review, Dr. Cherry wrote that in almost every clinical trial, the whole-cell vaccines were more efficacious than the acellular vaccines. That meant a certain balancing of risks and benefits, and ongoing discussion, as the changeover to DTaP has been linked to recent resurgences in the number of cases, though not necessarily in deaths, and Dr. Cherry argues that the increased number of reported cases may actually be a result of raised awareness and better testing. But even if there is more pertussis around in adults, thanks to the vaccines, this is no longer a deadly disease of young children.
Although a safe adult booster called the Tdap has now been developed, there is still a great deal of pertussis infection in adolescents and adults, and it often goes undiagnosed, even among doctors, because in adults it may not look that different from other coughs and colds.
But it can; for me, it was a miserable disease, though not particularly dangerous — I wasn’t at risk of dying from it, even if it was the worst cough I ever had. Adults don’t even tend to produce the characteristic “whoop,” which comes from sucking in air back across the closed glottis, after a paroxysm of coughing — if I’d been whooping, surely I would have diagnosed myself, or my colleagues at the health center would have diagnosed me.
I see this as a story that should help us appreciate the unending ingenuity of the science that finds ways to turn on our complicated immune responses without making us suffer through a disease that once choked the life out of countless babies.
At the same time we can understand that getting the most out of the body’s immune defenses can take some learning and some study, and that there can be trade-offs that you consider for the good of the individual patient or the good of the community. We vaccinate adults against pertussis now not only to protect them, but also to make sure that the vulnerable — in this case, infants — are less likely to be exposed, and in fact, vaccinating pregnant women with the adult booster turns out to be a good way to protect their newborns.
Dr. Cherry said that vaccinating all pregnant women with Tdap “will prevent virtually all deaths from pertussis in the first two months of life.”
Surely, as we live though this pandemic, we can take a moment to be grateful for the remarkable progress in vaccine technology that has given us vaccines that target Covid-19 so elegantly and specifically, and offers us ways to protect not only ourselves, but also those around us.
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January 11, 2021 at 05:00PM
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