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How Johnson & Johnson’s COVID-19 vaccine is different from Pfizer’s and Moderna’s

The delivery systems are different, but the end result is the same: protection from severe disease.

This July 2020 photo provided by Johnson & Johnson shows a vial of the COVID-19 vaccine in Belgium. The nation is poised to get a third vaccine against COVID-19, but health officials are concerned that at first glance the Johnson & Johnson shot may not be seen as equal to other options from Pfizer and Moderna.
This July 2020 photo provided by Johnson & Johnson shows a vial of the COVID-19 vaccine in Belgium. The nation is poised to get a third vaccine against COVID-19, but health officials are concerned that at first glance the Johnson & Johnson shot may not be seen as equal to other options from Pfizer and Moderna.Read more/ AP

UPDATE: The U.S. Food and Drug administration authorized the Johnson & Johnson vaccine.

Federal advisers voted Friday to recommend a COVID-19 vaccine made by Johnson & Johnson, meaning a third weapon for preventing the disease could be approved as early as Saturday and soon be available in U.S. clinics.

Like the two others — one made by Moderna Inc., the other a joint effort by Pfizer Inc. and BioNTech SE — the vaccine from J&J’s Janssen Biotech company seems to be very good at achieving the main public health goal: keeping people out of the hospital.

It relies on a different technology, but, like the others, shows no signs of causing severe, lasting side effects. And it has several advantages, among them that recipients need just one dose instead of two.

The estimated percentage of cases prevented in the J&J vaccine trial was lower than the numbers reported for the other two, but infectious-disease experts say that may not be a fair comparison, for a variety of reasons that we’ll get to below. (A key factor: The first two trials occurred earlier in the pandemic, before the emergence of coronavirus variants that may partly “escape” the protection afforded by the vaccines.)

The overwhelming advice from infectious-disease experts is to get whichever vaccine is available. Said University of Pennsylvania nursing school professor Alison Buttenheim, testifying before a congressional committee earlier this week:

“The best vaccine is the one you can get tomorrow.”

» READ MORE: Johnson and Johnson’s single-shot COVID-19 vaccine cleared by FDA

For a rundown on how the J&J vaccine stacks up against the others, we spoke to physician Nina Gentile, who oversaw the trial of the drug at Temple University Hospital, and Wistar Institute scientist Hildegund Ertl, who is developing a vaccine with a similar platform.

How the J&J vaccine works

All three vaccines consist of the genetic recipe for the person’s cells to make harmless fragments of the coronavirus: copies of the “spike” proteins that protrude from the surface of each virus particle.

The human immune system responds by making customized antibodies and other defenses should it ever encounter an actual infection. You cannot “get COVID” from any of the three drugs. It is biologically impossible. And the genetic instructions cannot become part of your DNA.

“People have to accept that these are safe vaccines,” Ertl said. “They are not going to harm them.”

» READ MORE: RNA vaccines have never been manufactured before, so making millions of doses was bound to take time. Here’s how it’s done.

While the three vaccines contain essentially the same genetic instructions, the delivery systems are different.

For the Moderna and Pfizer vaccines, the spike recipe is packaged in the form of RNA, inside microscopic spheres made from waxy molecules called lipids.

The J&J product, on the other hand, delivers the recipe using a different type of virus called an adenovirus. It has been modified so it cannot make copies of itself and cause disease. Even if it could, the disease in question would be mild: a form of the common cold.

When the vaccine is injected, the adenovirus particles penetrate cells in the person’s arm. The code for the spike protein — contained in the form of DNA, not RNA — enters each cell’s nucleus, prompting production of the spike. After several weeks, the immune system destroys these cells, but “remembers” how to respond in case it encounters an actual coronavirus.

Why the J&J vaccine has an edge

Because the J&J vaccine requires just one dose, more people can be immunized in a hurry. No need to worry about people failing to show up for their second shot. (Though new research suggests that the Pfizer vaccine, too, may achieve a substantial degree of protection after just one dose.)

Another key advantage of the J&J product: easy storage.

» READ MORE: Johnson & Johnson vaccine less potent than Pfizer, Moderna, but with just one shot

The Moderna and Pfizer vaccines must be kept in freezers to prevent the RNA from degrading. In the case of the Pfizer product, the temperatures for long-term storage must be ultra-cold, well below the reach of standard freezers, though the U.S. Food and Drug Administration recently said regular freezers are OK for two weeks before administration.

J&J’s adenovirus platform, on the other hand, is relatively stable and can be kept in refrigerators for months. And such drugs tend to be less expensive to produce, Ertl said.

How the numbers compare

Trials of the Moderna and Pfizer vaccines last year suggested that the drugs could prevent more than 90% of illnesses.

Results from the J&J trial reported this month suggest that vaccine prevented two-thirds of moderate-to-severe COVID cases in all countries and 74% of them in the U.S. That is still well above the levels of protection typically seen with vaccines for the flu.

» READ MORE: When your chance for a COVID-19 shot comes, experts say don’t worry about the numbers

And in those who became ill with COVID despite being vaccinated with the J&J drug, the severity of disease was generally less.

What’s more, the level of protection rose over time, said Gentile, a professor of emergency medicine at Temple’s Katz School of Medicine. At 28 days following administration of the vaccine, the number of severe and critically ill illnesses was 85% lower than in people who received a placebo.

“The benefits seem to be better when measured later,” she said. “The antibody levels seem to continue to rise over time.”

That’s one reason it is inappropriate to compare the J&J efficacy numbers with those for the other two vaccines, she said.

What’s more, the J&J drug was tested after the emergence of several virus variants, and at a time when COVID-19 transmission was far more widespread than during the Pfizer and Moderna trials.

» READ MORE: COVID-19 vaccines might be tweaked if variants get worse

The J&J vaccine trial consisted of more than 40,000 volunteers, including 530 at Temple. Half got vaccine and half got a placebo, though the latter will be able to get the real thing.

More vaccines on the horizon

The success of all three vaccines is an indication that the spike protein is a great teaching tool. In learning to recognize that innocuous fragment of the coronavirus, the immune system becomes equally good at recognizing the entire virus.

But viruses consist of other proteins besides the spike. At the Wistar Institute, Ertl is developing a two-pronged approach.

» READ MORE: Coronavirus variants prompt Moderna to develop extra booster vaccination

Using a different type of adenovirus from the one in the J&J vaccine, she is including genetic instructions both for the spike protein and for another protein found inside the coronavirus.

That one-two punch could be useful as the coronavirus continues to mutate, as the internal protein is expected to remain more stable, she said. The internal protein also tends to provoke a good response from a second type of immune defenders called T-cells.

Ertl plans to start testing that vaccine candidate in hamsters next month. As the pandemic continues, with many countries barely getting started in inoculating their populations, additional vaccines will be welcome.