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Single-shot Johnson & Johnson vaccine 66% effective against moderate and severe illness

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A single-shot coronavirus vaccine from pharmaceutical giant Johnson & Johnson was 66% effective at preventing moderate and severe illness in a massive global trial, findings released Friday show. But its performance was stronger in the United States and weaker in South Africa, where a worrisome coronavirus variant now dominates - a complicated result that reflects the evolution of the pandemic.

The results, reported in a news release, put a third vaccine on the horizon in the United States - one with logistical advantages that could simplify distribution and expand access to shots in the United States and worldwide.

Johnson & Johnson is expected to apply for emergency use authorization from the Food and Drug Administration next week. If the review follows the path of two earlier vaccine candidates, the shot could be authorized and available to the public by late February or early March.

The company has a $1.5 billion agreement with the federal government to support vaccine development and deliver 100 million doses to the United States by the end of June. But manufacturing lagged projected milestones earlier this month, and company officials declined to provide additional information on the pace of doses likely to be available month by month.

A communication challenge lies ahead for Johnson & Johnson and public health officials. Though less effective in its 44,000-person trial than 90-percent-plus effective vaccines made by Pfizer-BioNTech and Moderna, the Johnson & Johnson shot was tested at the height of the pandemic, in areas of the world where the virus had changed in ways that can elude parts of the immune response.

The vaccine was 72% effective at protecting against moderate to severe illness in the United States, but it was 66% effective in Latin America and 57% effective in South Africa, where concerning variants have taken root. It was 85% effective overall at preventing severe disease.

In the clinical trial, all cases of covid-related hospitalization and death - the outcomes that most people would like to avoid - were among participants who had received placebo shots.

The logistical advantages of the Johnson & Johnson vaccine should not be underestimated, experts said, particularly at a time when the pursuit of broad immunity to the virus through vaccines has assumed new urgency with the emergence of variants, sparking concerns that mutant viruses might escape vaccines, treatments and naturally acquired immunity.

"Vaccinating fast is going to be the message now, and vaccinating fast to reduce transmission and reduce the chance you have additional mutations," said Paul Stoffels, chief scientific officer for Johnson & Johnson. "The crisis is now hospitalization and death."

The one-shot vaccine could be a "game changer," according to Jonathan Temte, a vaccine expert at the University of Wisconsin School of Medicine and Public Health, because it can be stored for months at refrigerator temperature instead of the ultracold or frozen temperatures that have complicated the rollout of other coronavirus vaccines. The single shot could streamline the vaccination effort, freeing mass vaccination clinics from the need to recall people for boosters and the logistical complications accompanying that.

"Back in July and August, I was hoping we would see a vaccine that was 60% effective - in my mind, that would be great. And now we have had two that have hit the ball out of the park and set expectations spectacularly high, and that's not fair because we don't need a home run all the times we're up to bat," Temte said. A solution to the pandemic, he said, isn't a perfectly effective vaccine, but a vaccination campaign that can reach large swaths of the population as quickly as possible - comparing it to a baseball team that wins with steady base hits and bunts, not just home runs.

The FDA said a vaccine must be at least 50% effective to be authorized, a bar the Johnson & Johnson shot appears to have cleared, although the data will undergo careful and more detailed review by career FDA scientists and an outside panel of experts. Safety data will also be carefully reviewed, although the company said the shot had tolerable side effects, including fever and no serious safety concerns. There were no cases of anaphylaxis.

If the Johnson & Johnson shot is authorized, it would diversify the supply beyond two companies, something that many experts have hoped for in case of manufacturing delays or production lines going down because of contamination or other unexpected events. Temte recalled a shortage of the Hib vaccine given to children starting in late 2007, when problems with one manufacturer took production offline for more than a year, leaving the United States reliant on a single company.

Johnson & Johnson will manufacture its vaccine in the Netherlands and through partnerships with firms such as Emergent BioSolutions, a contract development and manufacturing company headquartered in Gaithersburg, Md.

The new vaccine uses a different technology than the two authorized vaccines in the United States, broadening the suite of tools to block the virus. The Johnson & Johnson vaccine employs a harmless cold virus to deliver a gene that carries the blueprint for the spiky protein found on the surface of the coronavirus. The virus infects cells, which then follow the genetic instructions to construct a replica of the coronavirus spike.

In contrast, the Pfizer and Moderna vaccines use a strip of genetic material called messenger RNA to instruct cells to build the spiky protein found on the surface of the coronavirus.

In both cases, the immune system learns to recognize the real virus by mustering an immune response to the spike.

The vaccine technology was able to move quickly into trials because it was preceded by decades of research.

In the early days of gene therapy, scientists hoped to use viruses to deliver good copies of genes that were missing or malfunctioning in people with diseases such as sickle cell anemia or cystic fibrosis. But the harmless cold virus they were experimenting with, an adenovirus, presented a major problem: It triggered an immune response.

Hildegund C.J. Ertl, an immune system expert and vaccine scientist at the Wistar Institute, said that when a scientific colleague working on gene therapy asked for her expertise, she told him, "Forget about gene therapy, what you have is a vaccine."

Scientists began to explore those cold viruses as a vaccine technology, particularly against HIV. In the early 2000s, when physician-scientist Dan Barouch set up his lab at Beth Israel Deaconess Medical Center in Boston, he aimed to invent an HIV vaccine, immersing himself in a corner of science that he describes as "an esoteric, slightly geeky area of research, that most people didn't really care about too much." In 2003, he partnered with a Dutch biotech company called Crucell and for two months lived in the Holiday Inn in Leiden in the Netherlands, learning how to grow and purify adenoviruses.

Barouch's lab selected one particular adenovirus, Ad26, to deliver the payload of genetic material that he hoped would teach the immune system to block HIV. That HIV vaccine, more than 15 years in the making, is now in clinical trials run by Janssen, a division of Johnson & Johnson that acquired Crucell.

But years of basic scientific work developing an adenovirus into an HIV vaccine, a notoriously difficult virus, built the scaffolding for a rapid response to new threats.

When a mosquito-borne virus caused babies to be born with abnormally small heads in 2015, the adenovirus technology became the framework for a Zika vaccine. That candidate was put back on the shelf as the threat receded, but it helped build confidence that a single shot could provide lasting immune response. Johnson & Johnson leveled the technology against Ebola, and a vaccine was approved by the European Medicines Agency last year.

"What we learned from Zika is we could go quickly, and that a single shot of the vaccine" led to durable immune responses, Barouch said. "That concept weighed heavily on us exactly a year ago in early January 2020, when it was feared that we had a problem with a new coronavirus."

Barouch's laboratory gathered at the Museum of Science in Boston on Jan. 10 for their annual retreat. They briefly discussed a mysterious new pneumonia that had sickened a few dozen people in China and killed one, considering whether they might need a vaccine. Later that night, Kathryn Stephenson, a physican-scientist at Beth Israel Deaconess, saw that Chinese scientists had uploaded the genome of the new coronavirus on Twitter and flagged it for Barouch. The team sprang to work, designing a dozen different potential vaccines.

Two weeks later, Barouch talked with Johan Van Hoof, global therapeutic head of vaccines at Janssen, about joining forces. An agreement was finalized in four days, shortcutting a process that Barouch said normally would have taken four months, if not 14 months.

It wasn't just the academic work that laid the groundwork for rapid development of a coronavirus vaccine. Gert Scheper, compound development team leader for Janssen Vaccines & Prevention, said that as the company worked on the technology over the years, it had begun scaling up manufacturing. That meant work had been done to learn how to grow the virus, not in a 50-liter vat for small clinical trials, but to a more massive 900-liter vat being used to manufacture the coronavirus vaccine.

"We could make use of that know-how," Scheper said. While he and others at the company have been steadily working on vaccines against HIV, RSV and other diseases, he said the pandemic changed everything.

"Then came covid, and for sure there's been a clear change in perspective within the company - and all the eyes are on us now," Scheper said.

Johnson & Johnson has a separate ongoing trial of two doses of the vaccine, because studies have demonstrated that a second dose can boost the immune response even higher.

But much of the debate over the next weeks is likely to be about how to best use a vaccine with a different efficacy profile and easier logistics. Experts warned that clinical trial results can't be directly compared, because of differences in how the trials are designed and when and where they are conducted. But anticipate that people will anyway.

Some people may want to choose which vaccine they get, asking whether they should wait for a more effective vaccine or skip the two-dose vaccine until a more convenient single shot is available, even as public health officials underscore that getting more people vaccinated with any authorized vaccine is the priority.

Jose Romero, health secretary of Arkansas and chairman of an advisory committee to the Centers for Disease Control and Prevention, said vaccines of different efficacy might end up targeted to different populations. He laid out a hypothetical scenario in which one vaccine was 90% effective and another was 60 to 70%.

"I'd want to use the vaccine with higher efficacy in my most vulnerable population," Romero said. "I'd think about 60 to 70% efficacy in a younger population where we know that the secondary morbidity and mortality is much lower."

Published : January 29, 2021

By : The Washington Post · Carolyn Y. Johnson