Individuals are ‘mixing and matching’ Covid vaccines over issues about variant

Dr. Angela Rasmussen, a virologist at Georgetown University, received a booster shot of Pfizer and BioNTech’s Covid-19 vaccine in late June, two months after she got Johnson & Johnson’s single dose.

Rasmussen picked J&J in April, when she was living in Seattle, because she was soon moving to Canada. She was concerned she wouldn’t be able to get the Pfizer vaccine, which requires two doses, due to the supply constraints in Canada at the time. J&J’s vaccine only requires one dose and recipients are considered fully vaccinated two weeks after receiving the shot.

But Rasmussen quickly changed her mind about getting Pfizer’s vaccine once she arrived in Canada. Delta, the highly transmissible variant first found in India that’s now in at least 124 countries, had begun making headlines, and studies at the time suggested a single dose of a Covid vaccine wouldn’t be enough protection.

“Once the supply issues were addressed here in Canada and there really wasn’t a supply shortage of the mRNA vaccines, I decided to go get a Pfizer shot just because I thought that at the very worst, it couldn’t hurt,” she told CNBC in a phone interview.

Some Americans say they are finding ways to get additional doses of the Covid vaccines, with some even going as far as receiving the extra shots from different companies. The thought is that by “mixing and matching” vaccines that use different platforms, people may be able to get broader protection against the coronavirus and its new variants. J&J’s vaccine uses an adenovirus, while Pfizer’s and Moderna’s two-dose vaccines use mRNA technology. It highlights the growing anxiety many Americans have over variants, including delta, already the dominant form of the disease in the U.S.

The practice is nothing new in other parts of the world. Last month, Germany’s government said Chancellor Angela Merkel received Moderna’s shot in June after getting AstraZeneca’s in April. Other countries, such as Italy, are also allowing those under the age of 60 who received a first dose of AstraZeneca’s vaccine to get a different shot when they get their second dose. South Korea said last month it would allow some 760,000 people to get different jabs because of shipment delays there.

Executives from Pfizer, Moderna and J&J have said they expect Americans will need booster shots, and Pfizer has said it plans to ask the FDA to authorize boosters as it sees signs of waning immunity. The Centers for Disease Control and Prevention does not currently recommend Americans mix Covid shots in most circumstances, and federal health officials say booster doses of the vaccines are not needed for otherwise healthy people at this time, although they may recommend it for the elderly or people with compromised immunity.

Since Rasmussen received her booster shot, a new study has suggested the J&J vaccine is much less effective against the delta and lambda variants than against the original virus. The researchers who led the study, which has not yet been peer-reviewed, now say they hope J&J recipients will eventually receive a booster shot of the Pfizer or Moderna vaccines.

To be sure, the new research is at odds with a study from the company, which found the shot is effective against delta, especially against severe disease and hospitalization, even eight months after inoculation. It is likely to reignite the debate of mixing and matching shots in the U.S. as the highly contagious delta variant continues to spread across the U.S.

“I would guess that those who received a single dose of Johnson & Johnson may need a booster of an mRNA vaccine than other people need boosters,” said Dr. Isaac Bogoch, an infectious disease professor at the University of Toronto, who was not involved in either study.

It’s important for scientists and public health officials to be “open-minded” about it, Bogoch said, adding he’s waiting for real-world data to back up the new study.

Israel also released preliminary data last week that showed the Pfizer vaccine is just 39% effective against the virus there, which officials attributed to the rapidly spreading delta variant. Its effectiveness against severe disease and death remained high, the data showed. U.S. and world health officials said they are looking at the Israeli research, which was not peer-reviewed and was scant on details.

The National Institutes of Health began an early stage trial in June looking at mixing and matching Covid vaccines. The trial will include adults who have received one of the three Covid vaccine regimens currently available in the U.S.: J&J, Moderna or Pfizer. Scientists there are trying to determine whether there are any advantages or drawbacks to using different boosters, according to the NIH.

Separate research from the United Kingdom published last month found mixing doses of the AstraZeneca vaccine, which shares similar technology to J&J’s, and an mRNA vaccine produced a stronger immune response against the coronavirus spike protein than just getting two doses of AstraZeneca. The study, called Com-COV, compared mixed two-dose schedules of Pfizer and AstraZeneca vaccines.

Another study, published in Nature Medicine on Monday, found adding the Pfizer or Moderna vaccines as a second dose to J&J led to a better immune response than just two doses of the J&J vaccine and was well tolerated. The vaccinations were performed between Jan. 10 and April 8.

Immunologically, it “makes sense” to follow up one vaccination with another shot that uses a different platform, according to Yale immunologist Akiko Iwasaki.

“The reason for this is because if you’re using a vectored vaccine, like the J&J or AstraZeneca, which use adenovirus, you generate antibodies against the vector so that your second shot with the same vector makes it less likely to induce a robust immune response,” she said.

Aside from Covid, mixing and matching vaccines that use different platforms is not something unusual, Iwasaki said. Looking at vaccine studies and trials for HIV, it’s “almost standard that people use different platforms to prime and boost,” she said.

Mixing vaccines may prevent the body from causing a sort of “mediated clearance of the vaccine itself,” where the shot is less effective, Iwasaki said.

“The spike protein that is used for the J&J and Moderna and Pfizer vaccines are virtually identical, so it is not like you’re getting cross-reactive protection against different variants,” she said. “But if you generate much higher levels of neutralizing antibodies, it will find epitopes in the variant that can also protect against the variant.”

Mixing the Covid vaccines appears to be safe but at the same time “we don’t know what we don’t know,” according to Dr. Dan Barouch, an immunologist at Harvard Medical School who helped develop the J&J vaccine.

“There’s limited data on the safety or efficacy of the approach, but theoretically, there is no reason that I can see that raises major safety concerns,” Barouch said. “But there are theoretical benefits in terms of the immune responses and potential improvement of efficacy.”

The World Health Organization’s chief scientist, Dr. Soumya Swaminathan, recently advised individuals against mixing and matching Covid vaccines from different manufacturers, saying the practice is a “data-free zone” and immunogenicity and safety both still need to be evaluated further.

“It’s a little bit of a dangerous trend here,” Swaminathan said during an online WHO briefing on July 13.

Still, some doctors are already suggesting immunosuppressed populations, such as patients living with cancer or those who have had organ transplants, might benefit from an extra dose of the same or another Covid vaccine, Barouch said.

A CDC advisory group on Thursday considered whether fully vaccinated Americans with weakened immune systems need a booster dose of a Covid vaccine after data shows they are less likely to have antibodies to fight the disease and more likely to suffer from a so-called breakthrough infection.

“The hardest to vaccinate people are those who are immunosuppressed,” Barouch said, adding early data shows the approach of mixing and matching vaccines may be safe and effective for those populations.

Rasmussen, the virologist at Georgetown University, said she didn’t experience any safety concerns or side effects, besides a sore arm, after getting a booster of Pfizer’s vaccine.

Matthew, a retired photographer from Los Angles, also said he didn’t experience any bad side effects after receiving a booster shot. Similar to Rasmussen, Matthew received a single dose of Pfizer’s vaccine several weeks after getting a single dose of J&J.

He said he decided to get a booster shot because he worried about his level of protection against variants. After speaking with his doctor about mixing and matching inoculations, Matthew concluded it was safe to get his second shot from Pfizer.

“When I got Johnson & Johnson I was tired for maybe a couple of days and I had intense pain in my calves for almost 48 hours,” said Matthew, 70, who asked that his last name not be used to protect his privacy. “I felt fine after the second dose.”

Dr. Paul Offit, who advises the FDA on Covid vaccines, said the CDC should provide “more direction” and create guidelines for how providers should be thinking about mixing and matching vaccines. Though he said he doesn’t expect the CDC to endorse the practice until there is more data and the U.S. studies are complete.

“It would be helpful to have some guidelines from the CDC on how to think about this,” he said. “More importantly, it would be helpful to have studies that are in hand, that are perfectly done that we can actually answer some of these questions.”

Likewise, Barouch said he doesn’t expect any new recommendations until there is more data.

“There’s going to be a lot of data soon and then there will be data-driven recommendations,” he said.

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