Covid-19 Vaccines Yield Breakthroughs in Long-Term Fight Against Infectious Disease

Researchers in gene-based technology produced a class of vaccines they believe can protect against all manner of outbreaks in the years to come

The pandemic has opened a new era for vaccines developed with gene-based technologies, techniques that have long stumped scientists and pharmaceutical companies, suggesting the possibility of future protection against a range of infectious disease.

Johnson & Johnson’s Covid-19 vaccine, which was authorized Saturday for use in the U.S., is at the vanguard of a class of shots designed to mobilize a person’s immune defenses against the disease. It will be the first Covid-19 vaccine administered in the U.S. that uses viral-vector technology, which employs an engineered cold virus to ferry coronavirus-fighting genetic code to the body’s cells.

J&J’s vaccine is the third to be authorized in the U.S. after ones from Pfizer Inc. PFE -0.28% and its partner, BioNTech SEBNTX -3.30% and Moderna Inc. MRNA -4.66% In a late-stage trial, J&J’s single-shot vaccine was 66% effective in preventing moderate to severe cases of the disease that has killed more than 500,000 people in the U.S. and about 2.5 million world-wide.

“This is one of those giant leap moments for us. These are fundamental shifts in how we will build vaccines for the future,” said C. Buddy Creech, director of Vanderbilt University’s vaccine research program. “I think this really ushers in a golden age of vaccinology.”

New vaccine technologies spurred by the pandemic are leading efforts to combat Covid-19 and herald a new arsenal of weapons for fighting lethal viruses in the future, infectious-disease researchers said, another example of how the fight against Covid has supercharged technological development.

First came messenger RNA vaccines from Pfizer and Moderna, efforts that after years of trying figured out how to use fatty particles to deliver synthesized genetic code to cells. J&J’s shot emerged after researchers finally found the right virus for ferrying tweaked DNA to the body.

Viral-vector Covid-19 vaccines developed in China and Russia also have been authorized for use in those and other countries. The Covid-19 vaccine developed by the University of Oxford and AstraZeneca PLC, which has been authorized in the U.K. and other countries, also is a viral-vector shot.

For years, vaccines for such infectious diseases as measles and polio were made from the viruses they targeted, in versions scientists rendered harmless. The shots rally the immune system by exposing people to the targeted virus. Yet such vaccines could take a decade or longer to develop, and manufacturing them took months.

The mRNA vaccines and J&J’s viral-vector shot—developed and tested in months—were propelled by new insights into the immune system that opened the door to engineering a better defense.

How Viral Vector Vaccines Work

Johnson & Johnson’s vaccine relies on a different mechanism for conferring immunity than traditional vaccines.

Almost like computer programmers, researchers wrote genetic instructions to muster the immune system’s molecular soldiers to fight the coronavirus. The vaccines deliver the programmed genetic code directly to cells in the body. The engineered DNA or RNA serve as a kind of genetic software, commanding the hardware of the human cell to wage battle.

Health authorities seeking to increase vaccinations have been looking forward to the arrival of J&J’s shot because it requires only one dose instead of two. Also, it can be kept at standard refrigerator temperatures for longer periods compared with the two vaccines now authorized for use in the U.S.

Covid-19 viral-vector vaccines are made by engineering a harmless type of virus—such as an adenovirus that can cause the common cold—to carry a gene from the coronavirus into the cell.

The vaccine’s DNA payload instructs the body’s cells to begin making a protein from the coronavirus. That production provokes an immune response to protect a vaccinated person if they are later exposed.

“The beauty is that you use natural systems, which are optimized by millions of years of evolution, to deliver what you want to have your body respond to,” said Vincent Munster, chief of the virus ecology section at the National Institute of Allergy and Infectious Disease, which helped with the AstraZeneca-Oxford vaccine.

These vaccines offer several advantages over shots using older technology. They seem to activate not just the antibodies that neutralize a virus but also the memory and T-cells that keep the immune defense alert for the long-term.

A healthcare worker fills a syringe from a vial with a dose of the Johnson & Johnson Covid-19 vaccine in South Africa.PHOTO: PHILL MAGAKOE/AGENCE FRANCE-PRESSE/GETTY IMAGES

Viral-vector vaccines also can be designed and manufactured relatively quickly, using the same basic building blocks, to fight an emerging infectious-disease outbreak. Scientists say the technology could yield approved vaccines against other infectious diseases, such as Zika and influenza.

Two viral-vector Ebola vaccines have been cleared for use. And a related technology uses the same technology for gene therapies to treat some cancers and rare genetic diseases.

“The future for pandemic response is that we want something along the lines of what J&J has done, a single shot able to induce immunity,” said Deborah Fuller, a vaccine researcher and professor of microbiology at the University of Washington School of Medicine.

The people problem

Scientists had chased viral-vector vaccines since the 1970s. One was approved to protect poultry by the U.S. Department of Agriculture in the 1990s, but it took much longer to find one for humans.

A major setback was a 2007 study finding that an experimental Merck & Co. viral-vector vaccine against HIV failed to protect people from the virus that causes AIDS. The problem turned out to be the common-cold virus that researchers used to deliver the genetic code.

Researchers found that those in the study with pre-existing immunity to the vaccine’s adenovirus strain appeared to have a higher susceptibility to HIV infection. Researchers suspected that vaccination on top of a pre-existing immunity may have activated the very part of the immune system that HIV tends to target, allowing the virus to spread in the body rather than be kept at bay. A Merck spokesman said a firm cause was never established.

Merck dropped the work, and there is still no effective HIV vaccine.

The company, however, later developed an Ebola vaccine, using a different viral vector called vesicular stomatitis, a virus that infects animals but rarely humans. In 2019, it became the first Ebola vaccine approved by the FDA.

One concern about viral-vector technology is whether people could develop an immunity to the vaccine itself, potentially making it less effective against new variants of the coronavirus or another type of outbreak.

“Over time, if you start routinely vaccinating people over and over with the same vaccine platform, the viral vector, you build up that immunity,” Dr. Fuller said. “It’s going to stop working after a while.”

A viral-vector Covid-19 vaccine developed in China didn’t perform as well in some people during testing because subjects had pre-existing immunity to the underlying virus that was used.

One way around the challenge is to use a virus from another species. The viral-vector vaccine from AstraZeneca PLC and its partner University of Oxford, which is being tested in the U.S., uses a chimpanzee adenovirus.

J&J took a chance on a different approach.


The company bet on viral-vector vaccines in 2011 with a $2.3 billion acquisition of the remaining stake it didn’t own in a Dutch biotechnology company, Crucell NV.

Though the world’s largest health-products maker by sales, J&J was a relative newcomer to vaccines. Crucell offered the New Brunswick, N.J., giant a chance to own a pipeline of hepatitis, influenza and cholera vaccines—and tap a market free of the cutthroat generic competition in drug sales.

Dan Barouch, a physician and immunologist at Beth Israel Deaconess Medical Center in Boston and a professor at Harvard Medical School.PHOTO: M. SCOTT BRAUER FOR THE WALL STREET JOURNAL

Crucell had been collaborating with Dan Barouch, a physician and immunologist at Beth Israel Deaconess Medical Center in Boston and professor at Harvard Medical School. He ran a lab exploring viral-vector use.

The same year that Merck’s HIV vaccine failed, Dr. Barouch and colleagues published work identifying types of adenoviruses different from the one Merck had used in its HIV shot.

One of the strains, dubbed Ad26, was less common in humans, and few people had a strong pre-existing immunity to it. That meant vaccines using the strain were less likely to fail. It later became the basis for J&J’s viral-vector vaccine research.

J&J began to deploy viral-vector technology, using AD26, against infectious-disease outbreaks, first Ebola and then Zika.

In 2015, during a deadly Ebola outbreak in West Africa, the company started studies of a two-vaccine Ebola regimen, shots given eight weeks apart. The first dose used Ad26 vector technology and the second dose a different design.

The studies showed the vaccines were safe and could provide an immune response. More than 100,000 people, mostly in Africa, have since received the J&J Ebola vaccine regimen under emergency-use approval.

A patient receiving a shot of the Johnson & Johnson vaccine for Ebola in the city of Goma, Democratic Republic of Congo, in November 2019.PHOTO: MSF/AGENCE FRANCE-PRESSE/GETTY IMAGES

After five years of development and testing, the European Commission in July last year approved J&J’s two-vaccine regimen against Ebola, a decision that validated the company’s viral-vector technology. Yet going into 2020, J&J had only a limited body of evidence that its viral-vector vaccines worked.

The Ebola studies, for instance, didn’t compare whether people receiving the vaccine had lower rates of Ebola than unvaccinated people who got a placebo. J&J had determined it wasn’t feasible to run that kind of controlled trial during a deadly outbreak. Instead, the EU relied on the evidence of positive immune-response results among those vaccinated against the Ebola virus.

When the pandemic hit, J&J’s Chief Scientific Officer Paul Stoffels said he asked his team members in January last year to explore making a vaccine against the new coronavirus spreading in China.

“Hey boss, we’re already doing it,” Dr. Stoffels recalled them saying.

The researchers studied the genetic sequence of the new coronavirus soon after it was published online by Chinese scientists. Then they sketched designs of potential vaccines, focusing on the spike protein found on the surface of the virus; Covid-19 uses it to attach and gain entry into human cells.

The idea was to employ Ad26 to carry DNA into human cells to instruct them make their own spike protein. That would trigger production of immune-system antibodies to fight off the actual virus in a vaccinated person, by binding to the spike protein and preventing it from entering cells.

Paul Stoffels, the chief scientific officer of Johnson & Johnson, in Leiden, Netherlands last year.PHOTO: JANSSEN VACCINES/REUTERS

By the end of January, Dr. Barouch got in touch with J&J researchers, and within a few days, they came up with about a dozen vaccine designs. Two months later, they landed on one candidate the company planned to test in animal and human studies, said Hanneke Schuitemaker, head of viral vaccine discovery at J&J.

In an early test, researchers at a contract laboratory in Maryland vaccinated rhesus macaques with J&J’s experimental shot, and, six weeks later, exposed them to the coronavirus.

After putting his children to bed on a Friday night in May, Dr. Barouch settled into his home office and opened an email with the results: After a single dose, there was no detectable virus in specimens from the lungs of all of the monkeys tested. “It gave me hope that this actually might work,” he said.

After Dr. Stoffels at J&J saw the monkey data, he said he, too, concluded, “Yes, we can do this.”

A scientist working on the Johnson & Johnson Covid-19 vaccine in Leiden, the Netherlands.PHOTO: JOHNSON & JOHNSON/ASSOCIATED PRESS

The results helped shape J&J’s decision to start a series of human tests—and to see if a single dose provided enough protection for widespread use during a pandemic emergency.

In July, J&J began testing its single-dose Covid-19 vaccine on more than 1,000 healthy adult volunteers. The company also ran parallel tests to see whether giving two doses about two months apart would be more effective.

The single-dose shot kept proving itself. In an early study, it produced antibodies to neutralize the coronavirus in people at levels that were stable for at least 71 days after vaccination.

That prompted J&J to run a large clinical trial. The study began in September and enrolled about 44,000 people in the U.S. and other countries. The results formed the basis for the FDA’s authorization, which, Dr. Stoffels said, capped “the work of 10 years of research.”

Read original article here.