One Vaccine-Schedule Change That Actually Makes Sense - The New Yorker

On January 5th, the Department of Health and Human Services, under the direction of Robert F. Kennedy, Jr., removed several vaccines from the universally recommended schedule for children: hepatitis A and B, meningococcal disease, rotavirus, influenza, and respiratory syncytial virus. These changes came after the removal, about seven months earlier, of the COVID vaccine. It’s become nearly impossible to find additional words to describe the vandalism of the American public-health system. In a statement, Andrew Racine, the president of the American Academy of Pediatrics, tried: “For decades, leading health experts, immunologists, and pediatricians have carefully reviewed new data and evidence as part of the immunization recommendation process, helping to keep newborns, infants, and children protected from diseases they could be exposed to in the United States as they develop and grow. Today’s decision, which was based on a brief review of other countries’ practices, upends this deliberate scientific process.” In the past thirty years or so, routine childhood vaccinations in the United States have prevented the deaths of an estimated 1.1 million children, and precluded thirty-two million hospitalizations.

But there is some good news. The new vaccine schedule contains one sensible and significant change. The human-papillomavirus (H.P.V.) vaccine, which protects against cervical cancer, was previously given as a series of two or three vaccinations; now it will be just one. The move might at first sound like little more than a reduced hassle—and maybe reckless, since there was good evidence in support of the three-shot regimen—but outside the U.S., in nineteen countries that switched to a one-dose regimen, the change led to some 18.5 million additional girls being vaccinated, averting an estimated three hundred thousand cases of cervical cancer. The hastiness with which H.H.S. revised the vaccine schedule suggests that the H.P.V. dosing shift came about almost incidentally, a side effect of a program of hacking away at vaccines generally. If so, there’s something fitting there. The realization that a single H.P.V. dose would work was itself, in large part, a felicitous by-product of the troubles that vaccine-research projects often encounter. Even the development of the H.P.V. vaccine involved some luck.

A mythical mischief-maker, the jackalope is a rabbit-like creature with antelope-like horns. In some tales, it has a gift for mimicking human voices. But not every horned rabbit is make-believe. In 1931, Richard Shope, a researcher at the Rockefeller Institute, noticed a tumor on the foot of a rabbit he had shot near Princeton, New Jersey; soon afterward, he began collecting and studying similar tumors on other wild rabbits. One day, the father of an administrator in Shope’s lab, visiting from Cherokee, Iowa, said that these growths were nothing compared with what he saw back home. “He said he had shot rabbits with horns out of the side of their heads like Texas steers, or out of the top of their noses like rhinoceroses,” Shope wrote, in unpublished notes. Shope went out to Iowa with the Iowan for a few days, to hunt for horned cottontail rabbits; before returning, he left five dollars and a bottle of glycerol, saying that he’d pay another five for any horns mailed to him.

Shope was a physician’s son, also from Iowa, who lost friends to the 1918 influenza epidemic—he went on to study the influenza virus. He had studied swine flu, as well; his swine-flu co-researcher died from a viral disease he was researching. From the growths on the cottontails—whose cause might plausibly have been genetic, environmental, or infectious—Shope isolated a previously unknown virus, a rabbit papillomavirus. Some of the growths turned into cancers, and, in his 1933 paper “Infectious Papillomatosis of Rabbits,” he demonstrated the first known example of a virus in a mammal causing cancer. He also developed a vaccine against the virus, which proved especially useful when a French bacteriologist thought to control the rabbit population on his property by importing two infected rabbits—which led within a year to the loss of approximately half the wild rabbits in France.

Hundreds of papillomaviruses have been documented in other mammals, such as humans. “My first job was in a gynecological-pathology rotation,” Margaret Stanley, an emeritus professor of epithelial biology at the University of Cambridge, told me. It was 1967, and she spent her time reading cervical Pap smears, which are used to detect cancerous or precancerous cells. “Cervical cancer was fascinating, because it quite obviously had an infectious cause,” she said. “But nobody could find out what the pathogen was.” By the mid-eighties, a team led by the German virologist Harald zur Hausen demonstrated that a human-papillomavirus infection was the main cause of most cervical cancers. (There are more than two hundred known human papillomaviruses, fourteen of which are known to potentially cause cancer.) This meant that preventing H.P.V. infection would mean preventing nearly all cervical cancers. The search for a vaccine was on.

Viruses, broadly speaking, are like zombies. They have none of the complex inner life of, say, bacteria, with their cytoplasm and their protein-making ribosomes. And viruses are generally not classed as “living”—an unstable classification, still under debate—because they cannot reproduce on their own. Instead, a virus sneaks into a living cell and takes over its systems of production, so that the infected cell’s factory replicates the virus’s genetic material rather than its own. Without a host cell, a virus is little more than scraps of genetic material waiting for a break.

The body’s defenses can often mount an effective attack on a virus, as long as the immune system “notices” it. Stanley wanted to understand why the body doesn’t tend to clear H.P.V., as it does so many other viral infections. She came to understand that what’s so clever about human papillomaviruses is that, in a sense, they’re not much trouble. H.P.V. infects epithelial cells, the outermost layer of cells—and doesn’t proceed much beyond there. Stanley explained, “Epithelial cells go through their life cycle. They’re born. They mature. They die. And they get sloughed off.” The fully formed virus particles, there in the sloughed-off cells, go on to infect other living epithelial cells. “It doesn’t need to kill a cell,” Stanley said. “The cell is going to die anyway. It’s a very efficient life cycle.” In this way, H.P.V.’s viral particles are unobtrusive. But then, sometimes, they cause the epithelial cells to become cancerous.

Developing an H.P.V. vaccine was distinctly challenging. One reason was that cancers from H.P.V. usually occur many years after the initial infection. A vaccine trial might need to run for decades, and such a delay could be life-costing, as well as impractical.

The epidemiologist Laura Koutsky, of the University of Washington, got around this problem by designing, with others, a double-blind study in which more than two thousand women were given three doses of the vaccine or an equivalent placebo and then screened every six months—not for cancer but, instead, simply for H.P.V.-16 infection. (H.P.V.-16 is the most common cancer-causing strain.) An early report, published a bit more than a year later, showed no H.P.V.-16 infections in the vaccinated group. Even ten years later, the women who had been immunized remained protected. “It was absolutely stunning,” Stanley said. In terms of extending life, getting an H.P.V. vaccine is as important for a woman as quitting smoking.

Ruanne Barnabas, a physician-scientist, grew up in South Africa, where her father worked as a botanist and her mother was a public-health doctor. “They weren’t maybe as organized as they could have been, so I would go to the hospital with my mom on the weekends,” she said. She also spent many afternoons in her dad’s laboratory, drawing botanical specimens. Her medical training, which coincided with the beginning of the AIDS epidemic, focussed on infectious disease, and she later continued her training with a Ph.D. in medicine and clinical epidemiology at Oxford. For her thesis, she constructed mathematical models using clinical trials of the first H.P.V. vaccines approved for use in England and in the U.S. The vaccine was capable of saving lives—the pressing question was how to increase access and lower costs. Cervical cancer is currently the fourth most common cancer in women globally, but in countries such as India and Kenya its prevalence is second only to breast cancer. Although the cost of H.P.V. vaccines is within reach for well-off countries, it is a stretch for most low- and middle-income ones.

It seemed pretty clear initially that H.P.V. vaccines would require a three-dose regimen. They are made of virus-like particles, rather than parts of the virus itself, and such vaccines (called protein-based vaccines) generally provoke only a weak immune response after the first dose. The follow-up doses boost that response. But getting people to turn up three times is an iffy proposition. This difficulty is amplified not only by ambient vaccine skepticism but also by the fact that H.P.V. is sexually transmitted and vaccines against it are ideally given to girls and young women. In Japan, in 2013, unfounded reports of the H.P.V. vaccine causing chronic pain or other neurological side effects spread in the media, leading the government temporarily to suspend its H.P.V. recommendation. Vaccination rates fell from seventy per cent to less than one per cent. In 2014, in northern Colombia, hundreds of school-age girls who had received the H.P.V. vaccine went to medical centers complaining of a racing heart, shortness of breath, and numbness in their arms and legs; a medical investigation concluded that the vaccines were not the cause, but the conclusion was poorly received.

In an H.P.V. vaccine trial that began in 2004 in Costa Rica, one of the most important findings came about by the by. Some seventy-five hundred women between the ages of eighteen and twenty-five were enrolled. However, for various reasons, pregnancy being a major one, about twenty per cent of them received fewer than three doses. But even the women who received only one developed antibody levels nine times higher than those found in naturally infected individuals. The vaccine efficacy among the groups remained essentially equal, even years down the line. Aimée Kreimer, the lead author on this discovery, suggested that maybe one dose was sufficient. “Kreimer was subjected to God knows how much skepticism,” Stanley, who counted herself among the disbelievers back then, said. “It was heresy for a protein-based vaccine to work with only one dose.”

Then a trial in India, begun in 2009, went even more wrong. The trial was looking at the efficacy of going from three H.P.V. doses to two. Led by the International Agency for Research Against Cancer, the trial enrolled twenty thousand girls and women. Before several months had passed, seven girls in a different H.P.V.-vaccine study—a demonstration study led by the nonprofit Program for Appropriate Technology in Health—died, and both the I.A.R.C. and PATH trials were stopped. (An investigation uncovered that one girl had drowned, another died from snake bite, two had swallowed poisonous pesticides, one died as a result of malaria, another of what was suspected to be a cerebral hemorrhage, and one of a high fever that Indian government investigators concluded was “very unlikely” to have resulted from the vaccine.) Some women had received one dose, and some two or three, but the women with one dose appeared to be as protected as those with more.

Still, reasonable skepticism of a one-dose approach remained, so Barnabas and an extensive team conducted a clinical trial, the KEN SHE study, in Kenya, which was about to become a lower-middle-income country, cutting it off from its international vaccine subsidies and pushing it to find cheaper solutions. Young women enrolled in the trial received either an H.P.V. vaccine or a meningococcal vaccine. “And at eighteen months we found very high efficacy for a single dose,” Barnabas said. Even after more than four years of follow-up, single-dose vaccination continued to show an efficacy of more than ninety-eight per cent. I asked Barnabas if she encountered much resistance to H.P.V. vaccines during the study. “In Kenya, if you ask people, ‘Does anyone know someone who’s been affected by cervical cancer?,’ half the hands in the room go up,” she said. The cancer is often diagnosed late in Kenya, and mortality is around fifty per cent. “It’s so disruptive to communities and families to lose women in the middle of their adult lives,” Barnabas added. In December, 2025, Kreimer was the lead author of a New England Journal of Medicine publication of the results of another trial in Costa Rica, the ESCUDDO trial: a controlled, randomized, double-blinded study with some twenty thousand participants that found that one dose of an H.P.V. vaccine was not inferior to two.

Some ninety countries now follow a single-dose regimen. Although the U.S. has been relatively late to make the switch, it will benefit in ways beyond the cost savings. Already, many Americans, for various reasons, receive only one dose. A close friend of mine had both of her children receive the first dose; she then came under enormous pressure from both her mother and her mother-in-law not to let them get further shots—they thought the vaccines were dangerous. My friend felt overwhelmed by the ongoing emotional pleas made by the respected older women in her life, and she didn’t send her kids in for doses two and three. “I’ve always said, the U.S. has in effect for years been a one-dose country,” Stanley told me. When my friend heard that one dose was sufficient, she was relieved. Then, not long afterward, her mother-in-law reached out to say that she had just learned that there was a vaccine that could prevent cancer, that she had never heard of such a thing, and that the kids should go and get it straight away.♦

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